Breast cancer is
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
that develops from
breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and secret ...
tissue. Signs of breast cancer may include a
lump
Lump may refer to:
* "Lump" (song), a 1995 song by The Presidents of the United States of America
* ''Lump'' (compilation album), a 2000 best-of album by The Presidents of the United States of America
* Lump (dog), a dog who inspired Pablo Pic ...
in the breast, a change in breast shape,
dimpling
A dimple, also called a gelasin (, ) is a small natural indentation in the flesh on a part of the human body, most notably in the cheek. Numerous cultures believe that cheek dimples are a good luck charm that entices people who perceive them as ...
of the skin,
milk rejection, fluid coming from the
nipple
The nipple is a raised region of tissue on the surface of the breast from which, in females, milk leaves the breast through the lactiferous ducts to feed an infant. The milk can flow through the nipple passively or it can be ejected by smooth mu ...
, a newly inverted nipple, or a red or scaly patch of skin.
In those with
distant spread of the disease, there may be
bone pain
Bone pain (also known medically by several other names) is pain coming from a bone, and is caused by damaging stimuli. It occurs as a result of a wide range of diseases or physical conditions or both, and may severely impair the quality of life. ...
, swollen
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s,
shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
, or
yellow skin.
Risk factors for developing breast cancer include
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, a
lack of physical exercise,
alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
,
hormone replacement therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
during
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
,
ionizing radiation
Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
, an early age at
first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer.
About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents,
including
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
and
BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
among others.
Breast cancer most commonly develops in cells from the lining of
milk ducts
Lactiferous ducts are ducts that converge and form a branched system connecting the nipple to the lobules of the mammary gland. When lactogenesis occurs, under the influence of hormones, the milk is moved to the nipple by the action of smooth mus ...
and the
lobules
In anatomy, a lobe is a clear anatomical division or extension of an organ (as seen for example in the brain, lung, liver, or kidney) that can be determined without the use of a microscope at the gross anatomy level. This is in contrast to the mu ...
that supply these ducts with milk.
Cancers developing from the ducts are known as
ductal carcinomas, while those developing from lobules are known as
lobular carcinoma
Lobular carcinoma is a form of tumor which primarily affects the lobules of a gland.
It is sometimes considered equivalent to "terminal duct carcinoma".
If not otherwise specified, it generally refers to breast cancer. Examples include:
* Lobular ...
s.
There are more than 18 other sub-types of breast cancer.
Some, such as
ductal carcinoma in situ
Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast. DCIS is classified as Stage 0. It rarely produces symptoms or a breast lump one can feel, typically being d ...
, develop from
pre-invasive lesions
A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased ...
.
The diagnosis of breast cancer is confirmed by taking a
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
of the concerning tissue.
Once the diagnosis is made, further tests are done to determine if the cancer has spread beyond the breast and which treatments are most likely to be effective.
The balance of benefits versus harms of
breast cancer screening
Breast cancer screening is the medical screening of asymptomatic, apparently healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening tests ...
is controversial. A 2013
Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
found that it was unclear if
mammographic screening does more harm than good, in that a large proportion of women who test positive turn out not to have the disease.
A 2009 review for the
US Preventive Services Task Force
The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
found evidence of benefit in those 40 to 70 years of age, and the organization recommends screening every two years in women 50 to 74 years of age.
The medications
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
or
raloxifene
Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to ...
may be used in an effort to prevent breast cancer in those who are at high risk of developing it.
Surgical removal of both breasts is another preventive measure in some high risk women.
In those who have been diagnosed with cancer, a number of treatments may be used, including surgery,
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
,
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
,
hormonal therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
, and
targeted therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
.
Types of surgery vary from
breast-conserving surgery
Breast-conserving surgery (BCS) refers to an operation that aims to remove breast cancer while avoiding a mastectomy. Different forms of this operation include: lumpectomy (tylectomy), wide local excision, segmental resection, and quadrantectom ...
to
mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
.
Breast reconstruction
Breast reconstruction is the surgical process of rebuilding the shape and look of a breast, most commonly in women who have had surgery to treat breast cancer. It involves using autologous tissue, prosthetic implants, or a combination of both wit ...
may take place at the time of surgery or at a later date.
In those in whom the cancer has spread to other parts of the body, treatments are mostly aimed at improving quality of life and comfort.
Outcomes for breast cancer vary depending on the cancer type, the
extent of disease, and the person's age.
The
five-year survival rate
The five-year survival rate is a type of survival rate for estimating the prognosis of a particular disease, normally calculated from the point of diagnosis. Lead time bias from earlier diagnosis can affect interpretation of the five-year surviva ...
s in England and the United States are between 80 and 90%.
In developing countries, five-year survival rates are lower.
Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases.
In 2018, it resulted in 2 million new cases and 627,000 deaths.
It is more common in developed countries
and is more than 100 times more common in women than
in men.
Signs and symptoms
![En Breast cancer illustrations](https://upload.wikimedia.org/wikipedia/commons/c/c1/En_Breast_cancer_illustrations.png)
Breast cancer most commonly presents as a
lump
Lump may refer to:
* "Lump" (song), a 1995 song by The Presidents of the United States of America
* ''Lump'' (compilation album), a 2000 best-of album by The Presidents of the United States of America
* Lump (dog), a dog who inspired Pablo Pic ...
that feels different from the rest of the breast tissue. More than 80% of cases are discovered when a person detects such a lump with the fingertips.
The earliest breast cancers, however, are detected by a
mammogram
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
.
Lumps found in lymph nodes located in the armpits
may also indicate breast cancer.
Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, a nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit and swelling beneath the armpit or around the collarbone. Pain ("
mastodynia
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...
") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other
breast health issues.
Another symptom complex of breast cancer is
Paget's disease of the breast
Paget's disease of the breast is a type of cancer that outwardly may have the appearance of eczema, with skin changes involving the nipple of the breast. The condition is an uncommon disease accounting for 1 to 4.3% of all breast cancers and was ...
. This syndrome presents as skin changes resembling eczema; such as redness, discoloration or mild flaking of the nipple skin. As Paget's disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half the women diagnosed with Paget's disease of the breast also have a lump in the breast.
Inflammatory breast cancer
Inflammatory breast cancer (IBC) is one of the most aggressive types of breast cancer. It can occur in women of any age (and, extremely rarely, in men, see male breast cancer). It is referred to as "inflammatory" due to its frequent presentation w ...
is a rare (only seen in less than 5% of breast cancer diagnosis) yet aggressive form of breast cancer characterized by the swollen, red areas formed on the top of the breast. The visual effects of inflammatory breast cancer is a result of a blockage of lymph vessels by cancer cells. This type of breast cancer is seen in more commonly diagnosed in younger ages, obese women and African American women. As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.
Mammary secretory carcinoma
Mammary secretory carcinoma (MSC), also termed secretory carcinoma of the breast, is a rare form of the breast cancers. MSC usually affects women but in a significant percentage of cases also occurs in men and children. Indeed, McDvitt and Stewart ...
(MSC) is a rare form of the
secretory carcinoma Secretory carcinoma was once used exclusively as a term for rare, slowly growing breast tumors without reference to their location in the breast. It is now termed mammary secretory carcinoma because secretory carcinoma has sometimes been used to nam ...
s that occurs exclusively in the breast.
It usually develops in adults but in a significant percentage of cases also affects children:
MSC accounts for 80% of all childhood breast cancers.
MSC lesions are typically slow growing, painless, small
ductal breast tumours that have invaded the tissue around their
ducts of origin, often spread to
sentinel lymph nodes
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...
and/or
axillary lymph nodes
The axillary lymph nodes or armpit lymph nodes are lymph nodes in the human armpit. Between 20 and 49 in number, they drain lymph vessels from the lateral quadrants of the breast, the superficial lymph vessels from thin walls of the chest and th ...
, but rarely metastasized to distant tissues.
These tumours typically have distinctive microscopic features and tumour cells that carry a balanced
genetic translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
in which part of the ''
NTRK3
Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the ''NTRK3'' gene.
TrkC is the high affinity catalyt ...
'' gene is fused to part of the ''
ETV6
ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ''ETV6'' (previously known as ''TEL'') gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly ...
'' gene
to form a
fusion gene A fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types of human neopla ...
, ''
ETV6-NTRK3''. This fusion gene encodes a
chimeric protein
Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' r ...
termed ETV6-NTRK3. The NTRK3 part of ETV6-NTRK3 protein has up-regulated
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
activity that stimulates two
signaling
In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...
pathways, the
PI3K/AKT/mTOR and
MAPK/ERK pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.
The signal starts when a signaling ...
s, which promote cell proliferation and survival and thereby may contribute to the development of MSC.
Conservative surgery, modified radical mastectomy, and radical mastectomy have been the most frequent procedures used to treat adults, while simple mastectomy, local excision with
sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...
biopsy, and complete axillary dissection have been recommended to treat children with MSC.
In all cases, long-term, e.g. >20 years, follow-up examinations are recommended.
The relatively rare cases of MSC that have metastasized to distant tissues have shown little or no responses to chemotherapy and radiotherapy. Three patients with metastatic disease had good partial responses to
Entrectinib
Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin r ...
, a drug that inhibits the tyrosine kinase activity of the ETV6-NTRK3 fusion protein.
Because of its slow growth and low rate of metastasis to distant tissues, individuals with MSC have had 20 year survival rates of 93.16%.
In rare cases, what initially appears as a
fibroadenoma
Fibroadenomas are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules (milk producing glands) and ducts (tubes that carry the milk to the nipple). These are surrounded by glandular, ...
(hard, movable non-cancerous lump) could in fact be a
phyllodes tumour
Phyllodes tumors (from Greek language, Greek: ''phullon'' leaf), also cystosarcoma phyllodes, cystosarcoma phylloides and phylloides tumor, are typically large, fast-growing masses that form from the periductal stromal cells of the breast. They acc ...
. Phyllodes tumours are formed within the
stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumours are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline or malignant.
Malignant tumours can result in metastatic tumours – secondary tumours (originating from the primary tumour) that spread beyond the site of origination. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung, and brain.
When cancer has reached such an invasive state, it is categorized as a stage 4 cancer, cancers of this state are often fatal. Common symptoms of stage 4 cancer include unexplained weight loss, bone and joint pain, jaundice and neurological symptoms. These symptoms are called
non-specific symptoms
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
because they could be manifestations of many other illnesses.
Rarely breast cancer can spread to exceedingly uncommon sites such as peripancreatic lymph nodes causing biliary obstruction leading to diagnostic difficulties.
![Brust Computertomographie mit Kontrastmittel Tumor](https://upload.wikimedia.org/wikipedia/commons/5/55/Brust_Computertomographie_mit_Kontrastmittel_Tumor.jpg)
Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Less than 20% of lumps, for example, are cancerous, and
benign breast disease
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...
s such as
mastitis
Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs ...
and
fibroadenoma
Fibroadenomas are benign breast tumours characterized by an admixture of stromal and epithelial tissue. Breasts are made of lobules (milk producing glands) and ducts (tubes that carry the milk to the nipple). These are surrounded by glandular, ...
of the breast are more common causes of breast disorder symptoms.
Risk factors
Risk factors can be divided into two categories:
* ''modifiable'' risk factors (things that people can change themselves, such as consumption of alcoholic beverages), and
* ''fixed'' risk factors (things that cannot be changed, such as age and physiological sex).
The primary risk factors for breast cancer are being female and older age. Other potential risk factors include genetics,
lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity. One study indicates that exposure to light pollution is a risk factor for the development of breast cancer.
If all adults maintained the healthiest possible lifestyles, including not drinking
alcoholic beverages
An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The cons ...
, maintaining a healthy
body composition
In physical fitness, body composition is used to describe the percentages of fat, bone, water, and muscle in human bodies. Because muscular tissue takes up less space in the body than fat tissue, body composition, as well as weight, determines ...
, never
smoking
Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have bee ...
, eating
healthful food, and other actions, then almost a quarter of breast cancer cases worldwide could be prevented.
The remaining three-quarters of breast cancer cases cannot be prevented through lifestyle changes.
Lifestyle
Drinking alcoholic beverages increases the risk of breast cancer, even among very light drinkers (women drinking less than half of one alcoholic drink per day).
The risk is highest among heavy drinkers.
Globally, about one in 10 cases of breast cancer is caused by women drinking alcoholic beverages.
Drinking alcoholic beverages is among the most common modifiable risk factors.
The correlation between
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
and breast cancer is anything but linear. Studies show that those who rapidly gain weight in adulthood are at higher risk than those who have been overweight since childhood. Likewise excess fat in the midsection seems to induce a higher risk than excess weight carried in the lower body. This implies that the food one eats is of greater importance than one's
BMI. Dietary factors that may increase risk include a high-fat diet and obesity-related
high cholesterol
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...
levels. Dietary iodine deficiency may also play a role. Evidence for fiber is unclear. A 2015 review found that studies trying to link fiber intake with breast cancer produced mixed results. In 2016, a tentative association between low fiber intake during adolescence and breast cancer was observed.
Smoking tobacco
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk.
In those who are long-term smokers, the relative risk is increased 35% to 50%.
A lack of physical activity has been linked to about 10% of cases.
Sitting
Sitting is a basic action and resting position in which the body weight is supported primarily by the bony ischial tuberosities with the buttocks in contact with the ground or a horizontal surface such as a chair seat, instead of by the lower l ...
regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.
Hormone therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...
to treat
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
is also associated with an increased risk of breast cancer. The use of
hormonal birth control
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...
does not cause breast cancer for most women; if it has an effect, it is small (on the order of 0.01% per user–year; comparable to the rate of
maternal mortality in the United States
Maternal mortality refers to the death of a woman during her pregnancy or up to a year after her pregnancy has terminated; this metric only includes causes related to the pregnancy, and does not include accidental causes. Some sources will define ...
), temporary, and offset by the users' significantly reduced risk of ovarian and endometrial cancers.
Among those with a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer. It is less certain whether hormonal contraceptives could increase the already high rates of breast cancer in women with mutations in the breast cancer susceptibility genes
''BRCA1'' or ''BRCA2''.
Breast feeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
reduces the risk of several types of cancers, including breast cancer.
In the 1980s, the
abortion–breast cancer hypothesis
The abortion–breast cancer hypothesis posits that having an induced abortion can increase the risk of getting breast cancer. This hypothesis is at odds with mainstream scientific opinion and is rejected by major medical professional organizatio ...
posited that
induced abortion
Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregnan ...
increased the risk of developing breast cancer.
This hypothesis was the subject of extensive scientific inquiry, which concluded that neither
miscarriage
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
s nor abortions are associated with a heightened risk for breast cancer.
Other risk factors include
radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes:
* ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
and
circadian
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
disruptions related to
shift-work
Shift work is an employment practice designed to make use of, or provide service across, all 24 hours of the clock each day of the week (often abbreviated as ''24/7''). The practice typically sees the day divided into shifts, set periods of t ...
and routine late-night eating. A number of chemicals have also been linked, including
polychlorinated biphenyls
Polychlorinated biphenyls (PCBs) are highly carcinogenic chemical compounds, formerly used in industrial and consumer products, whose production was banned in the United States by the Toxic Substances Control Act of 1976, Toxic Substances Contro ...
,
polycyclic aromatic hydrocarbons
A polycyclic aromatic hydrocarbon (PAH) is a class of organic compounds that is composed of multiple aromatic rings. The simplest representative is naphthalene, having two aromatic rings and the three-ring compounds anthracene and phenanthrene. P ...
, and
organic solvents
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for p ...
Although the radiation from
mammography
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.
Genetics
Genetics is believed to be the primary cause of 5–10% of all cases.
Women whose mother was diagnosed before 50 have an increased risk of 1.7 and those whose mother was diagnosed at age 50 or after has an increased risk of 1.4. In those with zero, one or two affected relatives, the risk of breast cancer before the age of 80 is 7.8%, 13.3%, and 21.1% with a subsequent mortality from the disease of 2.3%, 4.2%, and 7.6% respectively. In those with a first degree relative with the disease the risk of breast cancer between the age of 40 and 50 is double that of the general population.
In less than 5% of cases, genetics plays a more significant role by causing a
hereditary breast–ovarian cancer syndrome
Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several indi ...
.
This includes those who carry the
''BRCA1'' and ''BRCA2'' gene mutation.
These mutations account for up to 90% of the total genetic influence with a risk of breast cancer of 60–80% in those affected.
Other significant mutations include ''p53'' (
Li–Fraumeni syndrome
Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni, Jr., who first recognized the syndrom ...
), ''PTEN'' (
Cowden syndrome
Cowden syndrome (also known as Cowden's disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, ...
), and ''STK11'' (
Peutz–Jeghers syndrome
Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanos ...
), ''CHEK2'', ''ATM'', ''BRIP1'', and ''PALB2''.
In 2012, researchers said that there are four genetically distinct types of the breast cancer and that in each type, hallmark genetic changes lead to many cancers.
Other genetic predispositions include the density of the breast tissue and hormonal levels. Women with
dense breast tissue
Dense breast tissue, also known as dense breasts, is a condition of the breasts where a higher proportion of the breasts are made up of glandular tissue and fibrous tissue than fatty tissue. Around 40–50% of women have dense breast tissue and on ...
are more likely to get tumours and are less likely to be diagnosed with breast cancer – because the dense tissue makes tumours less visible on mammograms. Furthermore, women with naturally high estrogen and progesterone levels are also at higher risk for tumour development.
Medical conditions
Breast changes like
atypical ductal hyperplasia
Atypical ductal hyperplasia (ADH) is the term used for a benign lesion of the breast that indicates an increased risk of breast cancer.
The name of the entity is descriptive of the lesion; ADH is characterized by cellular proliferation (hyperplas ...
and
lobular carcinoma ''in situ'',
found in benign breast conditions such as
fibrocystic breast changes
Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal ...
, are correlated with an increased breast cancer risk.
Diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
might also increase the risk of breast cancer.
Autoimmune diseases such as
lupus erythematosus
Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blo ...
seem also to increase the risk for the acquisition of breast cancer.
The major causes of sporadic breast cancer are associated with hormone levels. Breast cancer is promoted by estrogen. This hormone activates the development of breast throughout puberty, menstrual cycles and pregnancy. The imbalance between estrogen and progesterone during the menstrual phases causes cell proliferation. Moreover, oxidative metabolites of estrogen can increase DNA damage and mutations. Repeated cycling and the impairment of repair process can transform a normal cell into pre-malignant and eventually malignant cell through mutation. During the premalignant stage, high proliferation of stromal cells can be activated by estrogen to support the development of breast cancer. During the ligand binding activation, the ER can regulate gene expression by interacting with estrogen response elements within the promotor of specific genes. The expression and activation of ER due to lack of estrogen can be stimulated by extracellular signals. Interestingly, the ER directly binding with the several proteins, including growth factor receptors, can promote the expression of genes related to cell growth and survival.
Raised
prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
levels in the blood are associated with increased risk of breast cancer. A meta-analysis of observational research with over two million individuals has suggested a moderate association of antipsychotic use with breast cancer, possibly mediated by prolactin-inducing properties of specific agents.
Pathophysiology
![Signal transduction pathways](https://upload.wikimedia.org/wikipedia/commons/b/b0/Signal_transduction_pathways.svg)
Breast cancer, like other
cancers
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...
, occurs because of an interaction between an environmental (external) factor and a genetically susceptible host. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when they lose their ability to stop dividing, to attach to other cells, to stay where they belong, and to die at the proper time.
Normal cells will self-destruct (
programmed cell death
Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage durin ...
) when they are no longer needed. Until then, cells are protected from programmed death by several protein clusters and pathways. One of the protective pathways is the
PI3K
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...
/
AKT
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transc ...
pathway; another is the
RAS
Ras or RAS may refer to:
Arts and media
* RAS Records Real Authentic Sound, a reggae record label
* Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service
* Rás 1, an Icelandic radio station
* Rás 2, an Icelandic radio stati ...
/
MEK/
ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of self-destructing when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the
PTEN protein turns off the PI3K/AKT pathway when the cell is ready for programmed cell death. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not self-destruct.
Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
Additionally, G-protein coupled
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
s have been associated with various cancers of the female reproductive system including breast cancer.
Abnormal
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
signaling in the interaction between
stromal cell
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucos ...
s and
epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
s can facilitate malignant cell growth.
In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.
In the United States, 10 to 20 percent of women with breast cancer or
ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
have a first- or second-degree relative with one of these diseases. Men with breast cancer have an even higher likelihood. The familial tendency to develop these cancers is called
hereditary breast–ovarian cancer syndrome
Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several indi ...
. The best known of these, the
''BRCA'' mutations, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as ''
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
'', ''
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
'' and ''
BRCA2
''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
'', occur in mechanisms to correct errors in
DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs.
However, there is strong evidence of residual risk variation that goes well beyond hereditary ''BRCA'' gene mutations between carrier families. This is caused by unobserved risk factors. This implicates environmental and other causes as triggers for breast cancers. The inherited mutation in ''BRCA1'' or ''BRCA2'' genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein). These carcinogens cause DNA damage such as DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2. However, mutations in ''BRCA'' genes account for only 2 to 3 percent of all breast cancers. Levin ''et al.'' say that cancer may not be inevitable for all carriers of ''BRCA1'' and ''BRCA2'' mutations.
About half of hereditary breast–ovarian cancer syndromes involve unknown genes. Furthermore, certain latent viruses, may decrease the expression of the ''BRCA1'' gene and increase the risk of breast tumours.
GATA-3
GATA3 is a transcription factor that in humans is encoded by the ''GATA3'' gene. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes.
The GATA3 transcription ...
directly controls the expression of estrogen receptor (ER) and other genes associated with epithelial differentiation, and the loss of GATA-3 leads to loss of differentiation and poor prognosis due to cancer cell invasion and metastasis.
Diagnosis
Most types of breast cancer are easy to diagnose by microscopic analysis of a sample – or
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
– of the affected area of the breast. Also, there are types of breast cancer that require specialized lab exams.
The two most commonly used screening methods, physical examination of the breasts by a healthcare provider and mammography, can offer an approximate likelihood that a lump is cancer, and may also detect some other lesions, such as a simple
cyst
A cyst is a closed sac, having a distinct envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac (like the manner in which ...
. When these examinations are inconclusive, a healthcare provider can remove a sample of the fluid in the lump for microscopic analysis (a procedure known as
fine needle aspiration
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...
, or fine needle aspiration and cytology, FNAC) to help establish the diagnosis. A needle aspiration can be performed in a healthcare provider's office or clinic. A local anesthetic may be used to numb the breast tissue to prevent pain during the procedure, but may not be necessary if the lump is not beneath the skin. A finding of clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, physical examination of the breasts, mammography, and FNAC can be used to diagnose breast cancer with a good degree of accuracy.
Other options for biopsy include a
core biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves extraction of sampling (medicine), sample Cell (biology), cells or Biologica ...
or
vacuum-assisted breast biopsy
Vacuum-assisted breast biopsy (VAB) is a minimally invasive procedure (biopsy) to help in the diagnosis of breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a cha ...
,
which are procedures in which a section of the breast lump is removed; or an
excisional biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
, in which the entire lump is removed. Very often the results of physical examination by a healthcare provider, mammography, and additional tests that may be performed in special circumstances (such as imaging by
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
or
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
) are sufficient to warrant excisional biopsy as the definitive diagnostic and primary treatment method.
File:Breast MRI T1W FSE ARC T2W FSE ARC T2W FSE IDEAL 09-arrow.jpg, MRI showing breast cancer
File:Breast cancer.JPG, Excised human breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and secret ...
tissue, showing an irregular, dense, white stellate
Stellate, meaning star-shaped, may refer to:
* Stellate cell
* Stellate ganglion
* Stellate reticulum
* Stellate veins
* Stellate trichomes (hairs) on plants
* Stellate laceration or incision Wound#Open
* Stellate fan-shaped Espalier (one form ...
area of cancer 2 cm in diameter, within yellow fatty tissue
File:Invasive Ductal Carcinoma 40x.jpg, High-grade invasive ductal carcinoma, with minimal tubule formation, marked pleomorphism
Pleomorphism may refer to:
* Pleomorphism (cytology), variability in the size and shape of cells and/or their nuclei
* Pleomorphism (microbiology), the ability of some bacteria to alter their shape or size in response to environmental conditions
...
, and prominent mitoses
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...
, 40x field
File:Breast carcinoma in a lymph node.jpg, Micrograph showing a lymph node invaded by ductal breast carcinoma, with an extension of the tumor beyond the lymph node
File:Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue.jpg, Neuropilin-2 expression in normal breast and breast carcinoma tissue
File:Mamma-CA.jpg, F-18 FDG PET/CT: A breast cancer metastasis to the right scapula
File:Needle Breast Biopsy.png, Needle breast biopsy
File:Manual compression elastography of invazive ductal carcinoma 00132.gif, Elastography shows stiff cancer tissue on ultrasound imaging.
File:Breast cancer ultrasound.jpg, Ultrasound image shows irregularly shaped mass of breast cancer.
File:Infiltrating breast carcinoma.jpg, Infiltrating (invasive) breast carcinoma
File:Mammo breast cancer wArrows.jpg, Mammograms
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
showing a normal breast (left) and a breast with cancer (right)
Classification
Breast cancers are classified by several grading systems. Each of these influences the
prognosis
Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
and can affect treatment response. Description of a breast cancer optimally includes all of these factors.
![Pie chart of incidence and prognosis of histopathologic breast cancer types](https://upload.wikimedia.org/wikipedia/commons/b/bd/Pie_chart_of_incidence_and_prognosis_of_histopathologic_breast_cancer_types.png)
* Histopathology. Breast cancer is usually classified primarily by its
histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as
ductal
Lafarge is a French industrial company specialising in cement, construction aggregates, and concrete. It is the world's largest cement manufacturer. It was founded in 1833 by Joseph-Auguste Pavin de Lafarge and is a part of the Holcim Group.
I ...
or lobular carcinoma. ''Carcinoma in situ'' is growth of low-grade cancerous or precancerous cells within a particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, ''invasive carcinoma'' does not confine itself to the initial tissue compartment.
* Grade.
Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers (the ones whose tissue is least like normal breast tissue) have a worse prognosis.
* Stage.
Breast cancer staging using the
TNM system is based on the size of the tumour (T), whether or not the tumour has spread to the
lymph
Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...
nodes (N) in the armpits, and whether the tumour has
metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.
The main stages are:
** Stage 0 is a pre-cancerous or marker condition, either
ductal carcinoma in situ
Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast. DCIS is classified as Stage 0. It rarely produces symptoms or a breast lump one can feel, typically being d ...
(DCIS) or
lobular carcinoma in situ
Lobular carcinoma ''in situ'' (LCIS) is an incidental microscopic finding with characteristic cellular morphology and multifocal tissue patterns. The condition is a laboratory diagnosis and refers to unusual cells in the lobules of the breast. T ...
(LCIS).
** Stages 1–3 are within the breast or regional lymph nodes.
** Stage 4 is
'metastatic' cancer that has a less favorable prognosis since it has spread beyond the breast and regional lymph nodes.
File:Diagram showing stage T1 breast cancer CRUK 244.svg, Stage T1 breast cancer
File:Diagram showing stage T2 breast cancer CRUK 252.svg, Stage T2 breast cancer
File:Diagram showing stage T3 breast cancer CRUK 259.svg, Stage T3 breast cancer
File:Stage 4 of Breast Cancer.jpg, Metastatic or stage 4 breast cancer
:Where available,
imaging studies
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
may be employed as part of the staging process in select cases to look for signs of metastatic cancer. However, in cases of breast cancer with low risk for metastasis, the risks associated with
PET scans
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
,
CT scans
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
, or
bone scans outweigh the possible benefits, as these procedures expose the person to a substantial amount of potentially dangerous ionizing radiation.
* Receptor status. Breast cancer cells have
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
on their surface and in their
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
and
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
*Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucle ...
. Chemical messengers such as
hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s bind to
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors:
estrogen receptor
Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
(ER),
progesterone receptor
The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone.
In humans, PR is encoded by a single ''PGR'' gene resid ...
(PR), and
HER2
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
.
ER+ cancer cells (that is, cancer cells that have estrogen receptors) depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g.
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
), and generally have a better prognosis. Untreated, HER2+ breast cancers are generally more aggressive than HER2- breast cancers,
but HER2+ cancer cells respond to drugs such as the
monoclonal antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ca ...
trastuzumab
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wit ...
(in combination with conventional chemotherapy), and this has improved the prognosis significantly. Cells that do not have any of these three receptor types (estrogen receptors, progesterone receptors, or HER2) are called
triple-negative, although they frequently do express receptors for other hormones, such as
androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
and
prolactin receptor
The prolactin receptor (PRLR) is a type I cytokine receptor encoded in humans by the ''PRLR'' gene on chromosome 5p13-14. It is the receptor for prolactin (PRL). The PRLR can also bind to and be activated by growth hormone (GH) and human placental ...
.
* DNA assays.
DNA testing
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
of various types including
DNA microarray
A DNA microarray (also commonly known as DNA chip or biochip) is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to ...
s have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type.
File:Diagram showing stage 1A breast cancer CRUK 199.svg, Stage 1A breast cancer
File:Diagram showing stage 1B breast cancer CRUK 202.svg, Stage 1B breast cancer
File:Diagram 1 of 2 showing stage 2A breast cancer CRUK 003.svg, Stage 2A breast cancer
File:Diagram 2 of 2 showing stage 2A breast cancer CRUK 009.svg, Stage 2A breast cancer
File:Diagram 1 of 3 showing stage 2B breast cancer CRUK 006.svg, Stage 2B breast cancer
File:Diagram 2 of 3 showing stage 2B breast cancer CRUK 012.svg, Stage 2B breast cancer
File:Diagram 3 of 3 showing stage 2B breast cancer CRUK 015.svg, Stage 2B breast cancer
File:Diagram 1 of 3 showing stage 3A breast cancer CRUK 007.svg, Stage 3A breast cancer
File:Diagram 2 of 3 showing stage 3A breast cancer CRUK 013.svg, Stage 3A breast cancer
File:Diagram 3 of 3 showing stage 3A breast cancer CRUK 016.svg, Stage 3A breast cancer
File:Diagram 1 of 2 showing stage 3B breast cancer CRUK 004.svg, Stage 3B breast cancer
File:Diagram 2 of 2 showing stage 3B breast cancer CRUK 010.svg, Stage 3B breast cancer
File:Diagram showing stage 4 breast cancer CRUK 228.svg, Stage 4 breast cancer
Screening
![BreastScreen Aotearoa](https://upload.wikimedia.org/wikipedia/commons/9/9a/BreastScreen_Aotearoa.JPG)
Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis under the assumption that early detection will improve outcomes. A number of screening tests have been employed including clinical and self
breast exams
Breast self-examination (BSE) is a breast cancer screening, screening method used in an attempt to detect early breast cancer. The method involves the woman herself looking at and feeling each breast for possible lumps, distortions or swelling.
B ...
,
mammography
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for
lumps or other abnormalities. Clinical breast exams are performed by health care providers, while self-breast exams are performed by the person themselves. Evidence does not support the effectiveness of either type of breast exam, as by the time a lump is large enough to be found it is likely to have been growing for several years and thus soon be large enough to be found without an exam.
Mammographic screening for breast cancer uses
X-ray
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...
s to examine the breast for any uncharacteristic masses or lumps. During a screening, the breast is compressed and a technician takes photos from multiple angles. A general mammogram takes photos of the entire breast, while a diagnostic mammogram focuses on a specific lump or area of concern.
A number of national bodies recommend breast cancer screening. For the average woman, the
U.S. Preventive Services Task Force
The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
and
American College of Physicians
The American College of Physicians (ACP) is a national organization of internists, who specialize in the diagnosis, treatment, and care of adults.Sokanu "What is an Internist?" Retrieved October 20, 2014 With 161,000 members, ACP is the largest ...
recommends mammography every two years in women between the ages of 50 and 74,
the
Council of Europe
The Council of Europe (CoE; french: Conseil de l'Europe, ) is an international organisation founded in the wake of World War II to uphold European Convention on Human Rights, human rights, democracy and the Law in Europe, rule of law in Europe. ...
recommends mammography between 50 and 69 with most programs using a 2-year frequency, while the European Commission recommends mammography from 45 to 75 every 2 to 3 years, and in Canada screening is recommended between the ages of 50 and 74 at a frequency of 2 to 3 years. The American Cancer Society also endorses that women ages 40 and older receive mammograms annually. These task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation.
The
Cochrane collaboration
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
(2013) states that the best quality evidence neither demonstrates a reduction in cancer specific, nor a reduction in all cause mortality from screening mammography.
When less rigorous trials are added to the analysis there is a reduction in mortality due to breast cancer of 0.05% (a decrease of 1 in 2000 deaths from breast cancer over 10 years or a relative decrease of 15% from breast cancer).
Screening over 10 years results in a 30% increase in rates of over-diagnosis and over-treatment (3 to 14 per 1000) and more than half will have at least one falsely positive test.
This has resulted in the view that it is not clear whether mammography screening does more good or harm.
Cochrane states that, due to recent improvements in breast cancer treatment, and the risks of false positives from breast cancer screening leading to unnecessary treatment, "it therefore no longer seems beneficial to attend for breast cancer screening" at any age. Whether MRI as a screening method has greater harms or benefits when compared to standard mammography is not known.
Prevention
Lifestyle
Women can reduce their risk of breast cancer by maintaining a healthy weight, reducing
alcohol use
An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains ethanol, a type of Alcohol (chemistry), alcohol that acts Alcohol (drug), as a drug and is produced by Ethanol fermentation, fermentat ...
, increasing physical activity, and
breast-feeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...
.
These modifications might prevent 38% of breast cancers in the US, 42% in the UK, 28% in Brazil, and 20% in China.
The benefits with moderate exercise such as brisk walking are seen at all age groups including postmenopausal women.
High levels of physical activity reduce the risk of breast cancer by about 14%.
Strategies that encourage regular physical activity and reduce obesity could also have other benefits, such as reduced risks of cardiovascular disease and diabetes.
A study that included data from 130,957 women of European ancestry found "strong evidence that greater levels of physical activity and less sedentary time are likely to reduce breast cancer risk, with results generally consistent across breast cancer subtypes".
The
American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
and the
American Society of Clinical Oncology
The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...
advised in 2016 that people should eat a diet high in vegetables, fruits, whole grains, and legumes. High intake of citrus fruit has been associated with a 10% reduction in the risk of breast cancer. Marine
omega-3 polyunsaturated fatty acids
Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
appear to reduce the risk.
High consumption of
soy
The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses.
Traditional unfermented food uses of soybeans include soy milk, from which tofu and ...
-based foods may reduce risk.
Pre-emptive surgery
Removal of both breasts before any cancer has been diagnosed or any suspicious lump or other lesion has appeared (a procedure known as "prophylactic bilateral
mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
" or "risk reducing mastectomy") may be considered in women with BRCA1 and BRCA2 mutations, which are associated with a substantially heightened risk for an eventual diagnosis of breast cancer. Evidence is not strong enough to support this procedure in anyone but women at the highest risk.
BRCA testing is recommended in those with a high family risk after genetic counseling. It is not recommended routinely.
This is because there are many forms of changes in BRCA genes, ranging from harmless
polymorphisms to obviously dangerous
frameshift mutations
A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels ( insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature ...
.
The effect of most of the identifiable changes in the genes is uncertain. Testing in an average-risk person is particularly likely to return one of these indeterminate, useless results. Removing the second breast in a person who has breast cancer (contralateral risk‐reducing mastectomy or CRRM) may reduce the risk of cancer in the second breast, however, it is unclear if removing the second breast in those who have breast cancer improves survival.
An increasing number women who test positive for faulty BRCA1 or BRCA2 genes choose to have
risk-reducing surgery. At the same time the average waiting time for undergoing the procedure is two-years which is much longer than recommended.
Medications
The
selective estrogen receptor modulators
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
reduce the risk of breast cancer but increase the risk of
thromboembolism
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
and
endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
.
There is no overall change in the risk of death.
They are thus not recommended for the prevention of breast cancer in women at average risk but it is recommended they be offered for those at high risk and over the age of 35. The benefit of breast cancer reduction continues for at least five years after stopping a course of treatment with these medications.
Aromatase inhibitor
Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exog ...
s (such as exemestane and anasatrozole) may be more effective than selective estrogen receptor modulators (such as tamoxifen) at reducing breast cancer risk and they are not associated with an increased risk of endometrial cancer and thromboembolism.
Management
The management of breast cancer depends on various factors, including the
stage
Stage or stages may refer to:
Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly British theatre newspaper
* Sta ...
of the cancer and the person's age. Treatments are more aggressive when the cancer is more advanced or there is a higher risk of recurrence of the cancer following treatment.
Breast cancer is usually treated with surgery, which may be followed by chemotherapy or radiation therapy, or both. A multidisciplinary approach is preferable. Hormone receptor-positive cancers are often treated with hormone-blocking therapy over courses of several years. Monoclonal antibodies, or other
immune-modulating
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
treatments, may be administered in certain cases of metastatic and other advanced stages of breast cancer, although this range of treatment is still being studied.
Surgery
![Mastectomie 02](https://upload.wikimedia.org/wikipedia/commons/b/b8/Mastectomie_02.jpg)
Surgery involves the physical removal of the tumour, typically along with some of the surrounding tissue. One or more lymph nodes may be biopsied during the surgery; increasingly the lymph node sampling is performed by a
sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasiz ...
biopsy.
Standard surgeries include:
*
Mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
: Removal of the whole breast.
*
Quadrantectomy
A quadrantectomy, also referred to as a segmental or partial mastectomy, is a breast-conserving surgery for breast cancer in which one quarter of breast tissue is removed along with muscles of the chest wall within a 2 to 3 centimeter radius of a t ...
: Removal of one-quarter of the breast.
*
Lumpectomy
Lumpectomy (sometimes known as a tylectomy, partial mastectomy, breast segmental resection or breast wide local excision) is a surgical removal of a discrete portion or "lump" of breast tissue, usually in the treatment of a malignant tumor or brea ...
: Removal of a small part of the breast.
Once the tumour has been removed, if the person desires,
breast reconstruction surgery
Breast reconstruction is the surgical process of rebuilding the shape and look of a breast, most commonly in women who have had surgery to treat breast cancer. It involves using autologous tissue, prosthetic implants, or a combination of both wit ...
, a type of
plastic surgery
Plastic surgery is a surgical specialty involving the restoration, reconstruction or alteration of the human body. It can be divided into two main categories: reconstructive surgery and cosmetic surgery. Reconstructive surgery includes craniofa ...
, may then be performed to improve the aesthetic appearance of the treated site.
Alternatively, women use
breast prostheses
Breast prostheses are breast forms intended to look like breasts. They are often used temporarily or permanently by women after mastectomy or lumpectomy procedures, but may also be used by for aesthetic purposes. There are a number of materials an ...
to simulate a breast under clothing, or choose a flat chest.
Nipple prosthesis
Nipple/Areola prostheses (prostheses is the plural of prosthesis) are made of silicone by breast prosthesis manufacturers and anaplastologists for breast cancer survivors who were treated for breast cancer with a mastectomy. Prostheses can be worn ...
can be used at any time following the mastectomy.
Medication
Medications used after and in addition to surgery are called
adjuvant therapy
Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in ...
. Chemotherapy or other types of therapy prior to surgery are called
neoadjuvant therapy
Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the size or ...
.
Aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
may reduce mortality from breast cancer when used with other treatments.
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.
Hormonal therapy
Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors). These ER+ cancers can be treated with drugs that either block the receptors, e.g.
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
, or alternatively block the production of estrogen with an
aromatase inhibitor
Aromatase inhibitors (AIs) are a class of drugs used in the treatment of breast cancer in postmenopausal women and in men, and gynecomastia in men. They may also be used off-label to reduce estrogen conversion when supplementing testosterone exog ...
, e.g.
anastrozole
Anastrozole, sold under the brand name Arimidex among others, is a medication used in addition to other treatments for breast cancer. Specifically it is used for hormone receptor-positive breast cancer. It has also been used to prevent breast ca ...
or
letrozole
Letrozole, sold under the brand name Femara among others, is an aromatase inhibitor medication that is used in the treatment of breast cancer.
It was patented in 1986 and approved for medical use in 1996. In 2020, it was the 257th most common ...
. The use of tamoxifen is recommended for 10 years. Tamoxifen increases the risk of
postmenopausal bleeding
Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductiv ...
,
endometrial polyp
An endometrial polyp or uterine polyp is a mass in the inner lining of the uterus.
They may have a large flat base (sessile) or be attached to the uterus by an elongated pedicle (pedunculated).
Pedunculated polyps are more common than sessile one ...
s,
hyperplasia
Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
, and
endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
; using tamoxifen with an
intrauterine system
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel in ...
releasing
levonorgestrel
Levonorgestrel is a hormonal medication which is used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand name Plan B One-Step among ...
might increase vaginal bleeding after one to two years, but reduces somewhat endometrial polyps and hyperplasia, but not necessarily endometrial cancer. Letrozole is recommended for five years.
Aromatase inhibitors are only suitable for women after menopause; however, in this group, they appear better than tamoxifen. This is because the active aromatase in postmenopausal women is different from the prevalent form in premenopausal women, and therefore these agents are ineffective in inhibiting the predominant aromatase of premenopausal women. Aromatase inhibitors should not be given to premenopausal women with intact ovarian function (unless they are also on treatment to stop their
ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
from working).
CDK inhibitor
A CDK (cyclin-dependent kinase) inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), ...
s can be used in combination with
endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
or aromatase therapy.
Chemotherapy
Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
is predominantly used for cases of breast cancer in stages 2–4, and is particularly beneficial in estrogen receptor-negative (ER-) disease. The chemotherapy medications are administered in combinations, usually for periods of 3–6 months. One of the most common regimens, known as "AC", combines
cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
with
doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...
. Sometimes a
taxane
Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA ap ...
drug, such as
docetaxel
Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-ce ...
, is added, and the regime is then known as "CAT". Another common treatment is cyclophosphamide,
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
, and
fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreat ...
(or "CMF"). Most chemotherapy medications work by destroying fast-growing and/or fast-replicating cancer cells, either by causing DNA damage upon replication or by other mechanisms. However, the medications also damage fast-growing normal cells, which may cause serious side effects. Damage to the heart muscle is the most dangerous complication of doxorubicin, for example.
Monoclonal antibodies
Trastuzumab
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wit ...
, a monoclonal antibody to HER2, has improved the five-year disease free survival of stage 1–3 HER2-positive breast cancers to about 87% (overall survival 95%). Between 25% and 30% of breast cancers
overexpress the HER2 gene or its protein product, and overexpression of HER2 in breast cancer is associated with increased disease recurrence and worse prognosis. Trastuzumab, however, is very expensive, and its use may cause serious side effects (approximately 2% of people who receive it develop significant heart damage). Another antibody
pertuzumab
Pertuzumab, sold under the brand name Perjeta, is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in earl ...
prevents HER2 dimerization and is recommended together with
trastuzumab
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wit ...
and chemotherapy in severe disease.
Radiation
Radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
is given after surgery to the region of the tumour bed and regional lymph nodes, to destroy microscopic tumour cells that may have escaped surgery. When given intraoperatively as
targeted intraoperative radiotherapy
Targeted intra-operative radiotherapy, also known as targeted IORT, is a technique of giving radiotherapy to the tissues surrounding a cancer after its surgical removal, a form of intraoperative radiation therapy. The technique was designed in ...
, it may also have a beneficial effect on tumour microenvironment. Radiation therapy can be delivered as
external beam radiotherapy
External beam radiotherapy (EBRT) is the most common form of radiotherapy (radiation therapy). The patient sits or lies on a couch and an external source of ionizing radiation is pointed at a particular part of the body. In contrast to brachyt ...
or as
brachytherapy
Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prosta ...
(internal radiotherapy). Conventionally radiotherapy is given ''after'' the operation for breast cancer. Radiation can also be given at the time of operation on the breast cancer. Radiation can reduce the risk of recurrence by 50–66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose and is considered essential when breast cancer is treated by removing only the lump (Lumpectomy or Wide local excision). In early breast cancer, partial breast irradiation does not give the same cancer control in the breast as treating the whole breast and may cause worse side effects.
Follow-up care
Care after primary breast cancer treatment, otherwise called 'follow-up care', can be intensive involving regular laboratory tests in asymptomatic people to try to achieve earlier detection of possible metastases. A review has found that follow-up programs involving regular physical examinations and yearly mammography alone are as effective as more intensive programs consisting of laboratory tests in terms of early detection of recurrence, overall survival and quality of life.
Multidisciplinary rehabilitation programmes, often including exercise, education and psychological help, may produce short-term improvements in functional ability, psychosocial adjustment and social participation in people with breast cancer.
Upper limb problems such as shoulder and arm pain, weakness and restricted movement are a common side effect after radiotherapy or breast cancer surgery. According to research in the UK, an exercise programme started 7–10 days after surgery can reduce upper limb problems.
Prognosis
Prognostic factors
The
stage
Stage or stages may refer to:
Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly British theatre newspaper
* Sta ...
of the breast cancer is the most important component of traditional classification methods of breast cancer, because it has a greater effect on the prognosis than the other considerations. Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis. The stage is raised by the invasiveness of disease to lymph nodes, chest wall, skin or beyond, and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones and close-to-normal cell behaviour (grading). Size is not a factor in staging unless the cancer is invasive. For example, ductal carcinoma in situ (DCIS) involving the entire breast will still be stage zero and consequently an excellent prognosis with a 10-year disease free survival of about 98%.
* Stage 1 cancers (and DCIS, LCIS) have an excellent prognosis and are generally treated with lumpectomy and sometimes radiation.
* Stage 2 and 3 cancers with a progressively poorer prognosis and greater risk of recurrence are generally treated with surgery (lumpectomy or mastectomy with or without
lymph node removal), chemotherapy (plus
trastuzumab
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wit ...
for HER2+ cancers) and sometimes radiation (particularly following large cancers, multiple positive nodes or lumpectomy).
* Stage 4, metastatic cancer, (i.e. spread to distant sites) has a poor prognosis and is managed by various combination of all treatments from surgery, radiation, chemotherapy and targeted therapies. Ten-year survival rate is 5% without treatment and 10% with optimal treatment.
The breast cancer grade is assessed by comparison of the breast cancer cells to normal breast cells. The closer to normal the cancer cells are, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear immature, will divide more rapidly, and will tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). The most widely used grading system is the Nottingham scheme.
Younger women with an age of less than 40 years or women over 80 years tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts may change with their menstrual cycles, they may be nursing infants, and they may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. There may also be biological factors contributing to a higher risk of disease recurrence for younger women with breast cancer.
Psychological aspects
Not all people with breast cancer experience their illness in the same manner. Factors such as age can have a significant impact on the way a person copes with a breast cancer diagnosis. Premenopausal women with estrogen-receptor positive breast cancer must confront the issues of early
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
induced by many of the chemotherapy regimens used to treat their breast cancer, especially those that use hormones to counteract ovarian function.
In women with non-metastatic breast cancer, psychological interventions such as
cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
can have positive effects on outcomes such as anxiety, depression and mood disturbance. Physical activity interventions may also have beneficial effects on health related quality of life, anxiety, fitness and physical activity in women with breast cancer following adjuvant therapy.
Epidemiology
![Breast cancer world map - Death - WHO2004](https://upload.wikimedia.org/wikipedia/commons/0/02/Breast_cancer_world_map_-_Death_-_WHO2004.svg)
Worldwide, breast cancer is the most-common invasive cancer in women.
Along with lung cancer, breast cancer is the most commonly diagnosed cancer, with 2.09 million cases each in 2018. Breast cancer affects 1 in 7 (14%) of women worldwide.
(The most common form of cancer is non-invasive
non-melanoma skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC ...
; non-invasive cancers are generally easily cured, cause very few deaths, and are routinely excluded from cancer statistics.) Breast cancer comprises 22.9% of invasive cancers in women
[ (cancer statistics often exclude non-melanoma skin cancers such as ]basal-cell carcinoma
Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...
, which are common but rarely fatal) and 16% of all female cancers. In 2012, it comprised 25.2% of cancers diagnosed in women, making it the most-common female cancer.
In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women and 6.0% of all cancer deaths for men and women together).
Lung cancer, the second most-common cause of cancer-related deaths in women, caused 12.8% of cancer deaths in women (18.2% of all cancer deaths for men and women together).
The incidence of breast cancer varies greatly around the world: it is lowest in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized
incidence rate
In epidemiology, incidence is a measure of the probability of occurrence of a given medical condition in a population within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time peri ...
s per 100,000 women are as follows: 18 in Eastern Asia, 22 in South Central Asia and sub-Saharan Africa, 26 in South-Eastern Asia, 26, 28 in North Africa and Western Asia, 42 in South and Central America, 42, 49 in Eastern Europe, 56 in Southern Europe, 73 in Northern Europe, 74 in Oceania, 78 in Western Europe, and 90 in North America. Metastatic breast cancer affects between 19% (United States) and 50% (parts of Africa) of women with breast cancer.
The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly attributed to the modern lifestyles.
Breast cancer is strongly related to age with only 5% of all breast cancers occurring in women under 40 years old. There were more than 41,000 newly diagnosed cases of breast cancer registered in England in 2011, around 80% of these cases were in women age 50 or older. Based on U.S. statistics in 2015 there were 2.8 million women affected by breast cancer.
In the United States, the
age-adjusted incidence of breast cancer per 100,000 women rose from around 102 cases per year in the 1970s to around 141 in the late-1990s, and has since fallen, holding steady around 125 since 2003. However, age-adjusted deaths from breast cancer per 100,000 women only rose slightly from 31.4 in 1975 to 33.2 in 1989 and have since declined steadily to 20.5 in 2014.
Multiple primary tumours
![Breast_quadrants_ABC](https://upload.wikimedia.org/wikipedia/commons/7/7f/Breast_quadrants_ABC.svg)
Multiple primary tumours can arise in different sites (as opposed to a single tumour spreading). These tumours can occur in both breasts (bilateral tumours), in different quadrants of a single breast (multi-centric cancer), or separate tumours within a single breast quadrant (multi-focal cancer).
Incidence of multi-centric and multi-focal breast cancers (MMBC) is increasing, partly due to improving mammography technology.
Incidence of MMBC is reported between 9 and 75% in high income countries, depending on criteria used.
For instance, China reported that only 2% of patients are defined as MMBC.
The reason for this difference is due to lack of uniformity in diagnosis.
Therefore, standardised method and criteria should be made in order to define the incidence of MMBC correctly.
Mutations in
tumour suppressor genes
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
such as
BRCA1 and BRCA2, the
PI3K/AKT/mTOR pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates A ...
and
PTEN can be related to formation of multiple primary breast cancers.
Diagnosis occurs via the same modalities as other breast cancers.
Mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
is the standard surgical treatment for multi centric breast cancer patients. Double
lumpectomies
Lumpectomy (sometimes known as a tylectomy, partial mastectomy, breast segmental resection or breast wide local excision) is a surgical removal of a discrete portion or "lump" of breast tissue, usually in the treatment of a malignant tumor or brea ...
, also labelled as breast conservative therapy (BCT), is an alternative and preferred surgical treatment to
mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
for early stage multi centric breast cancer patients.
The procedure of double lumpectomies involves the surgical ablation of the cancerous tumour foci and the surrounding breast tissues in different quadrant of the same breast.
The benefits of double lumpectomies are the avoidance of breast reconstruction surgery and minimal breast scarring. However, this surgical treatment is not preferable for patients with over two breast tumours within the same breast due to difficulty in removing all cancer cells.
Patients with multiple primary breast tumours may receive treatments such as chemotherapy, radiotherapy and
breast reconstruction surgery
Breast reconstruction is the surgical process of rebuilding the shape and look of a breast, most commonly in women who have had surgery to treat breast cancer. It involves using autologous tissue, prosthetic implants, or a combination of both wit ...
for the same indications as other breast cancer patients.
History
![Louis-Jacques Goussier Enzyklopädie Diderot Pl XXIX](https://upload.wikimedia.org/wikipedia/commons/6/69/Louis-Jacques_Goussier_Enzyklop%C3%A4die_Diderot_Pl_XXIX.jpg)
Because of its visibility, breast cancer was the form of cancer most often described in ancient documents.
Because autopsies were rare, cancers of the internal organs were essentially invisible to ancient medicine. Breast cancer, however, could be felt through the skin, and in its advanced state often developed into
fungating lesion A fungating lesion is a skin lesion that fungates, that is, becomes like a fungus in its appearance or growth rate. It is marked by ulcerations (breaks on the skin or surface of an organ) and necrosis (death of living tissue) and usually presents ...
s: the tumour would become
necrotic
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
(die from the inside, causing the tumour to appear to break up) and
ulcerate
Ulcerate is a New Zealand-based extreme metal band formed by guitarist Michael Hoggard and drummer Jamie Saint Merat in 2000. The band have released six studio albums to date. The band have been featured in numerous articles as one of New Zea ...
through the skin, weeping fetid, dark fluid.
The oldest discovered evidence of breast cancer is from Egypt and dates back 4200 years, to the
Sixth Dynasty
The Sixth Dynasty of ancient Egypt (notated Dynasty VI), along with the Third, Fourth and Fifth Dynasty, constitutes the Old Kingdom of Dynastic Egypt.
Pharaohs
Known pharaohs of the Sixth Dynasty are listed in the table below. Manetho acc ...
.
The study of a woman's remains from the necropolis of
Qubbet el-Hawa
Qubbet el-Hawa or "Dome of the Wind" is a site on the western bank of the Nile, opposite Aswan, that serves as the resting place of ancient nobles and priests from the Old and Middle Kingdoms of ancient Egypt. The necropolis in use from the F ...
showed the typical destructive damage due to
metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
spread.
The
Edwin Smith Papyrus
The Edwin Smith Papyrus is an ancient Egyptian medical text, named after Edwin Smith who bought it in 1862, and the oldest known surgical treatise on trauma. From a cited quotation in another text, it may have been known to ancient surgeons as t ...
describes eight cases of tumours or ulcers of the breast that were treated by
cauterization
Cauterization (or cauterisation, or cautery) is a medical practice or technique of burning a part of a body to remove or close off a part of it. It destroys some tissue in an attempt to mitigate bleeding and damage, remove an undesired growth, or ...
. The writing says about the disease, "There is no treatment." For centuries, physicians described similar cases in their practices, with the same conclusion. Ancient medicine, from the time of the Greeks through the 17th century, was based on
humoralism
Humorism, the humoral theory, or humoralism, was a system of medicine detailing a supposed makeup and workings of the human body, adopted by Ancient Greek and Roman physicians and philosophers.
Humorism began to fall out of favor in the 1850s ...
, and thus believed that breast cancer was generally caused by imbalances in the fundamental fluids that controlled the body, especially an excess of
black bile
Melancholia or melancholy (from el, µέλαινα χολή ',Burton, Bk. I, p. 147 meaning black bile) is a concept found throughout History of medicine#Greece and Roman Empire, ancient, medieval medicine of Western Europe, medieval and Lear ...
.
Alternatively it was seen as
divine punishment
Divine judgment means the judgment of God or other supreme beings within a religion.
Ancient beliefs
In ancient Sumerian religion, the sun-god Utu and his twin sister Inanna were believed to be the enforcers of divine justice. Utu, as th ...
.
Mastectomy for breast cancer was performed at least as early as AD 548, when it was proposed by the court physician
Aetios of Amida Aetius, Aëtius, or Aetios (Ἀέτιος) may refer to:
People
* Aetius (philosopher), 1st- or 2nd-century doxographer and Eclectic philosopher
* Aëtius of Antioch, 4th-century Anomean theologian
* Flavius Aetius, Western Roman commander in chi ...
to
Theodora
Theodora is a given name of Greek origin, meaning "God's gift".
Theodora may also refer to:
Historical figures known as Theodora
Byzantine empresses
* Theodora (wife of Justinian I) ( 500 – 548), saint by the Orthodox Church
* Theodora of ...
.
It was not until doctors achieved greater understanding of the circulatory system in the 17th century that they could link breast cancer's spread to the
lymph nodes
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
in the armpit. In the early 18th century the French surgeon
Jean Louis Petit
Jean-Louis Petit (13 March 1674 – 20 April 1750) was a French surgeon and the inventor of a screw-type tourniquet. He was first enthusiastic about anatomy and received a master's certificate in surgery in Paris in 1700. He became a member of th ...
performed total mastectomies that included removing the
axillary lymph nodes
The axillary lymph nodes or armpit lymph nodes are lymph nodes in the human armpit. Between 20 and 49 in number, they drain lymph vessels from the lateral quadrants of the breast, the superficial lymph vessels from thin walls of the chest and th ...
, as he recognized that this reduced recurrence.
Petit's work built on the methods of the surgeon
Bernard Peyrilhe
Bernard Peyrilhe (1735–1804) was a French surgeon, known as one of the founders of experimental cancer research. Peyrilhe was born in Pompignan, and became a lecturer at the Paris School of Surgery (').
In 1773, Peyrilhe was studying for a P ...
, who in the 17th century additionally removed the
pectoral muscle
Pectoral muscles (colloquially referred to as "pecs") are the muscles that connect the front of the human chest with the bones of the upper arm and shoulder. This region contains four muscles that provide movements to the upper limbs or ribs.
P ...
underlying the breast, as he judged that this greatly improved the prognosis. But poor results and the considerable risk to the patient meant that physicians did not share the opinion of surgeons such as
Nicolaes Tulp
Nicolaes Tulp (9 October 1593 – 12 September 1674) was a Dutch surgeon and mayor of Amsterdam. Tulp was well known for his upstanding moral character and as the subject of Rembrandt's famous painting ''The Anatomy Lesson of Dr. Nicolaes Tulp'' ...
, who in the 17th century proclaimed "the sole remedy is a timely operation". The eminent surgeon
Richard Wiseman
Richard J. Wiseman (born 17 September 1966) is a Professor of the Public Understanding of Psychology at the University of Hertfordshire in the United Kingdom. He has written several psychology books. He has given keynote addresses to The Royal ...
documented in the mid 17th century that following 12 mastectomies, two patients died during the operation, eight patients died shortly after the operation from progressive cancer and only two of the 12 patients were cured.
Physicians were conservative in the treatment they prescribed in the early stages of breast cancer. Patients were treated with a mixture of
detox purges,
blood letting
Bloodletting (or blood-letting) is the withdrawal of blood from a patient to prevent or cure illness and disease. Bloodletting, whether by a physician or by leeches, was based on an ancient system of medicine in which blood and other bodily fl ...
and traditional remedies that were supposed to lower acidity, such as the alkaline
arsenic
Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but ...
.
When in 1664
Anne of Austria
Anne of Austria (french: Anne d'Autriche, italic=no, es, Ana María Mauricia, italic=no; 22 September 1601 – 20 January 1666) was an infanta of Spain who became Queen of France as the wife of King Louis XIII from their marriage in 1615 unti ...
was diagnosed with breast cancer, the initial treatment involved compresses saturated with
hemlock juice. When the lumps increased the King's physician commenced a treatment with arsenic
ointment
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
s.
The royal patient died 1666 in atrocious pain.
Each failing treatment for breast cancer led to the search for new treatments, spurring a market in remedies that were advertised and sold by
quacks,
herbalist
Herbal medicine (also herbalism) is the study of pharmacognosy and the use of medicinal plants, which are a basis of traditional medicine. With worldwide research into pharmacology, some herbal medicines have been translated into modern remed ...
s,
chemist
A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe th ...
s and
apothecaries
''Apothecary'' () is a mostly archaic term for a medicine, medical professional who formulates and dispenses ''materia medica'' (medicine) to physicians, surgeons, and patients. The modern chemist (British English) or pharmacist (British and Nor ...
. The lack of
anesthesia
Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
and
antiseptics
An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...
made
mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. A mastectomy is usually carried out to treat breast cancer. In some cases, women believed to be at high risk of breast cancer have the operat ...
a painful and dangerous ordeal.
In the 18th century, a wide variety of anatomical discoveries were accompanied by new theories about the cause and growth of breast cancer. The investigative surgeon
John Hunter claimed that neural fluid generated breast cancer. Other surgeons proposed that milk within the
mammary duct
Lactiferous ducts are ducts that converge and form a branched system connecting the nipple to the lobules of the mammary gland. When lactogenesis occurs, under the influence of hormones, the milk is moved to the nipple by the action of smooth mus ...
s led to cancerous growths. Theories about trauma to the breast as cause for
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
changes in breast tissue were advanced. The discovery of
breast lump
A breast mass, also known as a breast lump, is a localized swelling that feel different from the surrounding tissue. Breast pain, nipple discharge, or skin changes may be present. Concerning findings include masses that are hard, do not move e ...
s and swellings fueled controversies about hard
tumours
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
and whether lumps were benign stages of cancer. Medical opinion about necessary immediate treatment varied.
The surgeon
Benjamin Bell
Benjamin Bell of Hunthill FRSE FRCSEd (6 September 1749 – 5 April 1806) is considered to be the first Scottish scientific surgeon. He is commonly described as the father of the Edinburgh school of surgery,Richardson BWS, Martin MSM. Discipl ...
advocated removal of the entire breast, even when only a portion was affected.
![William Stewart Halsted, Surgical papers Wellcome L0004968](https://upload.wikimedia.org/wikipedia/commons/6/69/William_Stewart_Halsted%2C_Surgical_papers_Wellcome_L0004968.jpg)
Breast cancer was uncommon until the 19th century, when improvements in sanitation and control of deadly
infectious disease
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s resulted in dramatic increases in lifespan. Previously, most women had died too young to have developed breast cancer.
In 1878, an article in ''
Scientific American
''Scientific American'', informally abbreviated ''SciAm'' or sometimes ''SA'', is an American popular science magazine. Many famous scientists, including Albert Einstein and Nikola Tesla, have contributed articles to it. In print since 1845, it i ...
'' described historical treatment by pressure intended to induce local ischemia in cases when surgical removal were not possible.
William Stewart Halsted
William Stewart Halsted, M.D. (September 23, 1852 – September 7, 1922) was an American surgeon who emphasized strict aseptic technique during surgical procedures, was an early champion of newly discovered anesthetics, and introduced several ...
started performing
radical mastectomies
Radical mastectomy is a surgical procedure involving the removal of breast, underlying chest muscle (including pectoralis major and pectoralis minor), and lymph nodes of the axilla as a treatment for breast cancer. Breast cancer is the most comm ...
in 1882, helped greatly by advances in general surgical technology, such as
aseptic technique
Asepsis is the state of being free from disease-causing micro-organisms (such as pathogenic bacteria, viruses, pathogenic fungi, and parasites). There are two categories of asepsis: medical and surgical. The modern day notion of asepsis is deriv ...
and anesthesia. The Halsted radical mastectomy often involved removing both breasts, associated lymph nodes, and the underlying chest muscles. This often led to long-term pain and disability, but was seen as necessary to prevent the cancer from recurring.
Before the advent of the Halsted radical mastectomy, 20-year survival rates were only 10%; Halsted's surgery raised that rate to 50%.
Breast cancer staging systems were developed in the 1920s and 1930s to determining the extent to which a cancer has developed by growing and spreading.
The first
case-controlled study on breast cancer epidemiology was done by
Janet Lane-Claypon
Janet Elizabeth Lane-Claypon, Lady Forber (3 February 1877 – 17 July 1967) was an English physician. She was one of the founders of the science of epidemiology, pioneering the use of cohort studies and case-control studies.
Early life and ...
, who published a comparative study in 1926 of 500 breast cancer cases and 500 controls of the same background and lifestyle for the British Ministry of Health.
Radical mastectomies remained the standard of care in the USA until the 1970s, but in Europe, breast-sparing procedures, often followed by
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
, were generally adopted in the 1950s.
In 1955
George Crile Jr.
George Washington "Barney" Crile Jr. (November 3, 1907 – September 11, 1992)"George Crile Jr." ''Contemporary Authors Online''. Detroit: Gale, 2001. Gale Biography In Context. Web. 26 July 2011. was an American surgeon. He was a significant inf ...
published ''Cancer and Common Sense'' arguing that cancer patients needed to understand available treatment options. Crile became a close friend of the environmentalist
Rachel Carson
Rachel Louise Carson (May 27, 1907 – April 14, 1964) was an American marine biologist, writer, and conservationist whose influential book ''Silent Spring'' (1962) and other writings are credited with advancing the global environmental m ...
, who had undergone a Halsted radical mastectomy in 1960 to treat her malign breast cancer.
The US oncologist
Jerome Urban Jerome Urban (1914-1991) was an American surgical oncologist who promoted superradical mastectomies until 1963, when the lack of difference in ten-year survival rates convinced him that it worked no better than the less-mutilating radical mastectom ...
promoted superradical mastectomies, taking even more tissue, until 1963, when the ten-year survival rates proved equal to the less-damaging radical mastectomy.
Carson died in 1964 and Crile went on to published a wide variety of articles, both in the popular press and in medical journals, challenging the widespread used of the Halsted radical mastectomy. In 1973 Crile published ''What Women Should Know About the Breast Cancer Controversy''. When in 1974
Betty Ford
Elizabeth Anne Ford (; formerly Warren; April 8, 1918 – July 8, 2011) was the first lady of the United States from 1974 to 1977, as the wife of President Gerald Ford. As first lady, she was active in social policy and set a precedent as a pol ...
was diagnosed with breast cancer, the options for treating breast cancer were openly discussed in the press.
During the 1970s, a new understanding of
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
led to perceiving cancer as a systemic illness as well as a localized one, and more sparing procedures were developed that proved equally effective.
In the 1980s and 1990s, thousands of women who had successfully completed standard treatment then demanded and received high-dose
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
s, thinking this would lead to better long-term survival. However, it proved completely ineffective, and 15–20% of women died because of the brutal treatment.
The 1995 reports from the
Nurses' Health Study
The Nurses Health Study is a series of prospective studies that examine epidemiology and the long-term effects of nutrition, hormones, environment, and nurses' work-life on health and disease development. The studies have been among the largest inv ...
and the 2002 conclusions of the
Women's Health Initiative
The Women's Health Initiative (WHI) was a series of clinical studies initiated by the U.S. National Institutes of Health (NIH) in 1991, to address major health issues causing morbidity and mortality in postmenopausal women. It consisted of three ...
trial conclusively proved that
hormone replacement therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
significantly increased the incidence of breast cancer.
Society and culture
Before the 20th century, breast cancer was feared and discussed in hushed tones, as if it were shameful. As little could be safely done with primitive surgical techniques, women tended to suffer silently rather than seeking care. When surgery advanced, and long-term survival rates improved, women began
raising awareness
Consciousness raising (also called awareness raising) is a form of activism popularized by United States feminists in the late 1960s. It often takes the form of a group of people attempting to focus the attention of a wider group on some cause or ...
of the disease and the possibility of successful treatment. The "Women's Field Army", run by the American Society for the Control of Cancer (later the
American Cancer Society
The American Cancer Society (ACS) is a nationwide voluntary health organization dedicated to eliminating cancer. Established in 1913, the society is organized into six geographical regions of both medical and lay volunteers operating in more than ...
) during the 1930s and 1940s was one of the first organized campaigns. In 1952, the first peer-to-peer
support group
In a support group, members provide each other with various types of help, usually nonprofessional and nonmaterial, for a particular shared, usually burdensome, characteristic. Members with the same issues can come together for sharing coping str ...
, called "Reach to Recovery", began providing post-mastectomy, in-hospital visits from women who had survived breast cancer.
The
breast cancer movement of the 1980s and 1990s developed out of the larger
feminist movement
The feminist movement (also known as the women's movement, or feminism) refers to a series of social movements and political campaigns for Radical politics, radical and Liberalism, liberal reforms on women's issues created by the inequality b ...
s and
women's health movement
The presence of women in medicine, particularly in the practicing fields of surgery and as physicians, has been traced to the earliest of history. Women have historically had lower participation levels in medical fields compared to men with occu ...
of the 20th century.
This series of political and educational campaigns, partly inspired by the politically and socially effective AIDS awareness campaigns, resulted in the widespread acceptance of second opinions before surgery, less invasive surgical procedures, support groups, and other advances in care.
Pink ribbon
![Pink ribbon](https://upload.wikimedia.org/wikipedia/commons/b/b5/Pink_ribbon.svg)
A
pink ribbon
The pink ribbon is an international symbol of breast cancer awareness. Pink ribbons, and the color pink in general, identify the wearer or promoter with the breast cancer brand and express moral support for women with breast cancer. Pink ribb ...
is the most prominent symbol of breast cancer awareness. Pink ribbons, which can be made inexpensively, are sometimes sold as fundraisers, much like
poppies on Remembrance Day. They may be worn to honor those who have been diagnosed with breast cancer, or to identify products that the manufacturer would like to sell to consumers that are interested in breast cancer.
In the 1990s breast cancer awareness campaigns were launched by US based corporations. As part of these
cause related marketing
Cause marketing is marketing done by a for-profit business that seeks to both increase profits and to better society in accordance with corporate social responsibility, such as by including activist messages in advertising.
A similar phrase, ca ...
campaigns corporations donated to a variety of breast cancer initiatives for every pink ribbon product that was purchased.
> ''
The Wall Street Journal
''The Wall Street Journal'' is an American business-focused, international daily newspaper based in New York City, with international editions also available in Chinese and Japanese. The ''Journal'', along with its Asian editions, is published ...
'' noted "that the strong emotions provoked by breast cancer translate to a company's
bottom line
In business and accounting, net income (also total comprehensive income, net earnings, net profit, bottom line, sales profit, or credit sales) is an entity's income minus cost of goods sold, expenses, depreciation and amortization, interest, a ...
". While many US corporations donated to existing breast cancer initiatives others such as
Avon established their own breast cancer foundations on the back of pink ribbon products.
Wearing or displaying a pink ribbon has been criticized by the opponents of this practice as a kind of
slacktivism
Slacktivism (a portmanteau of ''slacker'' and ''activism'') is the practice of supporting a political or social cause by means such as social media or online petitions, characterized as involving very little effort or commitment. Additional form ...
, because it has no practical positive effect. It has also been criticized as
hypocrisy
Hypocrisy is the practice of engaging in the same behavior or activity for which one criticizes another or the practice of claiming to have moral standards or beliefs to which one's own behavior does not conform. In moral psychology, it is the ...
, because some people wear the pink ribbon to show good will towards women with breast cancer, but then oppose these women's practical goals, like
patient rights
A patient's bill of rights is a list of guarantees for those receiving medical care. It may take the form of a law or a non-binding declaration. Typically a patient's bill of rights guarantees patients information, fair treatment, and autonomy ov ...
and
anti-pollution legislation
Environmental law is a collective term encompassing aspects of the law that provide protection to the environment. A related but distinct set of regulatory regimes, now strongly influenced by environmental legal principles, focus on the manage ...
.
Critics say that the feel-good nature of pink ribbons and pink consumption distracts society from the lack of progress on preventing and curing breast cancer.
It is also criticized for reinforcing gender stereotypes and
objectifying
In social philosophy, objectification is the act of treating a person, as an object or a thing. It is part of dehumanization, the act of disavowing the humanity of others. Sexual objectification, the act of treating a person as a mere object of sex ...
women and their breasts.<
In 2002
Breast Cancer Action
Breast Cancer Action (BCAction) is a U.S.-based grassroots education and activist organization driven by and supporting people living with breast cancer. It was founded in 1990 by Elenore Pred, Susan Claymon, and Linda Reyes. Based in San Franci ...
launched the "Think Before You Pink" campaign against
pinkwashing to target businesses that have co-opted the pink campaign to promote products that cause breast cancer, such as alcoholic beverages.
Breast cancer culture
In her 2006 book ''Pink Ribbons, Inc.: Breast Cancer and the Politics of Philanthropy'' Samantha King claimed that breast cancer has been transformed from a serious disease and individual tragedy to a market-driven industry of survivorship and corporate sales pitch.
In 2010 Gayle Sulik argued that the primary purposes or goals of breast cancer culture are to maintain breast cancer's dominance as the pre-eminent women's health issue, to promote the appearance that society is doing something effective about breast cancer, and to sustain and expand the social, political, and financial power of breast cancer activists.
In the same year
Barbara Ehrenreich
Barbara Ehrenreich (, ; ; August 26, 1941 – September 1, 2022) was an American author and political activist. During the 1980s and early 1990s, she was a prominent figure in the Democratic Socialists of America. She was a widely read and awar ...
published an opinion piece in ''
Harper's Magazine
''Harper's Magazine'' is a monthly magazine of literature, politics, culture, finance, and the arts. Launched in New York City in June 1850, it is the oldest continuously published monthly magazine in the U.S. (''Scientific American'' is older, b ...
'', lamenting that in breast cancer culture, breast cancer therapy is viewed as a
rite of passage
A rite of passage is a ceremony or ritual of the passage which occurs when an individual leaves one group to enter another. It involves a significant change of status in society. In cultural anthropology the term is the Anglicisation of ''rite ...
rather than a disease. To fit into this mold, the woman with breast cancer needs to normalize and feminize her appearance, and minimize the disruption that her health issues cause anyone else. Anger, sadness, and negativity must be silenced. As with most cultural models, people who conform to the model are given social status, in this case as
cancer survivor
A cancer survivor is a person with cancer of any type who is still living. Whether a person becomes a survivor at the time of diagnosis or after completing treatment, whether people who are actively dying are considered survivors, and whether ...
s. Women who reject the model are shunned, punished and shamed. The culture is criticized for treating adult women like little girls, as evidenced by "baby" toys such as pink
teddy bear
A teddy bear is a stuffed toy in the form of a bear. Developed apparently simultaneously by toymakers Morris Michtom in the U.S. and Richard Steiff under his aunt Margarete Steiff's company in Germany in the early 20th century, the teddy bear, ...
s given to adult women.
Emphasis
In 2009 the US science journalist
Christie Aschwanden
Christie Aschwanden is an American journalist and the former lead science writer at ''FiveThirtyEight''. Her 2019 book ''GOOD TO GO: What the Athlete in All of Us Can Learn From the Strange Science of Recovery'', was a New York Times bestseller. ...
criticized that the emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own.
Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and precancers, even while overlooking serious cancers. According to the cancer researcher
H. Gilbert Welch
H. Gilbert Welch is an American academic physician and cancer researcher. He was an internist at the Veterans Administration Medical Center in White River Junction, Vermont, as well as a professor of medicine at the Dartmouth Institute for Health ...
, screening mammography has taken the "brain-dead approach that says the best test is the one that finds the most cancers" rather than the one that finds dangerous cancers.
In 2002 it was noted that as a result of breast cancer's high visibility, the statistical results can be misinterpreted, such as the claim that one in eight women will be diagnosed with breast cancer during their lives – a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95.
By 2010 the breast cancer survival rate in Europe was 91% at one years and 65% at five years. In the USA the five-year survival rate for localized breast cancer was 96.8%, while in cases of
metastases
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
it was only 20.6%. Because the prognosis for breast cancer was at this stage relatively favorable, compared to the prognosis for other cancers, breast cancer as cause of death among women was 13.9% of all cancer deaths. The second most common cause of death from cancer in women was lung cancer, the most common cancer worldwide for men and women. The improved survival rate made breast cancer the most prevalent cancer in the world. In 2010 an estimated 3.6 million women worldwide have had a breast cancer diagnosis in the past five years, while only 1.4 million male or female survivors from lung cancer were alive.
Health disparities in breast cancer
There are ethnic disparities in the mortality rates for breast cancer as well as in breast cancer treatment. Breast cancer is the most prevalent cancer affecting women of every ethnic group in the United States. Breast cancer incidence among black women aged 45 and older is higher than that of white women in the same age group. White women aged 60–84 have higher incidence rates of breast cancer than Black women. Despite this, Black women at every age are more likely to succumb to breast cancer.
Breast cancer treatment has improved greatly in recent years, but black women are still less likely to obtain treatment compared to white women.
Risk factors such as socioeconomic status, late-stage, or breast cancer at diagnosis, genetic differences in tumour subtypes, differences in health care access all contribute to these disparities. Socioeconomic determinants affecting the disparity in breast cancer illness include poverty, culture, as well as social injustice. In Hispanic women, the incidence of breast cancer is lower than in non-Hispanic women but is often diagnosed at a later stage than white women with larger tumors.
Black women are usually diagnosed with breast cancer at a younger age than white women. The median age of diagnosis for Black women is 59, in comparison to 62 in White women. The incidence of breast cancer in Black women has increased by 0.4% per year since 1975 and 1.5% per year among Asian/Pacific Islander women since 1992. Incidence rates were stable for non-Hispanic White, Hispanics, and Native women. The five-year survival rate is noted to be 81% in Black women and 92% in White women. Chinese and Japanese women have the highest survival rates.
Poverty is a major driver for disparities related to breast cancer. Low-income women are less likely to undergo breast cancer screening and thus are more likely to have a late-stage diagnosis.
Ensuring women of all ethnic groups receive equitable health care can positively affect these disparities.
Pregnancy
Pregnancy at an early age decreases the risk of developing breast cancer later in life.
[ The risk of breast cancer also declines with the number of children a woman has.] Breast cancer then becomes more common in the 5 or 10 years following pregnancy but then becomes less common than among the general population. These cancers are known as postpartum breast cancer and have worse outcomes including an increased risk of distant spread of disease and mortality. Other cancers found during or shortly after pregnancy appear at approximately the same rate as other cancers in women of a similar age.
Diagnosing new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average in many pregnant or recently pregnant women. Some imaging procedures, such as MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
s (magnetic resonance imaging), CT scan
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
s, ultrasounds, and mammogram
Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, typically through d ...
s with fetal shielding are considered safe during pregnancy; some others, such as PET scan
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
s are not.
Treatment is generally the same as for non-pregnant women. However, radiation is normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries to speed the start of treatment are not uncommon. Surgery is generally considered safe during pregnancy, but some other treatments, especially certain chemotherapy drugs given during the first trimester
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
, increase the risk of birth defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
s and pregnancy loss (spontaneous abortions and stillbirths). Elective abortions are not required and do not improve the likelihood of the mother surviving or being cured.
Radiation treatments may interfere with the mother's ability to breastfeed her baby because it reduces the ability of that breast to produce milk and increases the risk of mastitis
Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs ...
. Also, when chemotherapy is being given after birth, many of the drugs pass through breast milk to the baby, which could harm the baby.
Regarding future pregnancy among breast cancer survivor
A cancer survivor is a person with cancer of any type who is still living. Whether a person becomes a survivor at the time of diagnosis or after completing treatment, whether people who are actively dying are considered survivors, and whether ...
s, there is often fear of cancer recurrence. On the other hand, many still regard pregnancy and parenthood to represent normality, happiness and life fulfillment.
Hormones
Birth control
In breast cancer survivors, non-hormonal birth control
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
methods such as the copper intrauterine device (IUD) should be used as first-line options. Progestogen
Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...
-based methods such as depot medroxyprogesterone acetate
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of birt ...
, IUD with progestogen
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel int ...
or progestogen only pill
Progestogen-only pills or progestin-only pills (POP) are contraceptive pills that contain only synthetic progestogens ( progestins) and do not contain estrogen. They are colloquially known as mini pills.
Although such pills are sometimes called ...
s have a poorly investigated but possible increased risk of cancer recurrence, but may be used if positive effects outweigh this possible risk.
Menopausal hormone replacement
In breast cancer survivors, it is recommended to first consider non-hormonal options for menopausal
Menopause, also known as the climacteric, is the time in women's lives when Menstruation, menstrual periods stop permanently, and they are no longer fertility, able to bear children. Menopause usually occurs between the age of 47 and 54. Medic ...
effects, such as bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
s or selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists a ...
s (SERMs) for osteoporosis, and vaginal estrogen Vaginal estrogen is a form of estrogen that is delivered by intravaginal administration. Vaginally administered estrogens are thereby exerting their effects mainly in the nearby tissue, with more limited systemic effects compared to orally adminis ...
for local symptoms. Observational studies of systemic hormone replacement therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
after breast cancer are generally reassuring. If hormone replacement is necessary after breast cancer, estrogen-only therapy or estrogen therapy with an intrauterine device with progestogen
A hormonal intrauterine device (IUD), also known as a intrauterine system (IUS) with progestogen and sold under the brand name Mirena among others, is an intrauterine device that releases a progestogenic hormonal agent such as levonorgestrel int ...
may be safer options than combined systemic therapy.
Research
Treatments are being evaluated in clinical trials. This includes individual drugs, combinations of drugs, and surgical and radiation techniques Investigations include new types of targeted therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks ...
, cancer vaccine
A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...
s, oncolytic virotherapy
An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viru ...
, gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
and immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
.
The latest research is reported annually at scientific meetings such as that of the American Society of Clinical Oncology
The American Society of Clinical Oncology (ASCO) is a professional organization representing physicians of all oncology sub-specialties who care for people with cancer. Founded in 1964 by Fred Ansfield, Harry Bisel, Herman Freckman, Arnoldus G ...
, San Antonio Breast Cancer Symposium, and the St. Gallen Oncology Conference in St. Gallen, Switzerland. These studies are reviewed by professional societies and other organizations, and formulated into guidelines for specific treatment groups and risk category.
Fenretinide
Fenretinide (''N''-(4-hydroxyphenyl)retinamide; 4-HPR) (INN) is a synthetic retinoid derivative. Retinoids are substances related to vitamin A. It has been investigated for potential use in the treatment of cancer, as well as in the treatment of c ...
, a retinoid
The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth.
Retinoids have many important functions throughout t ...
, is also being studied as a way to reduce the risk of breast cancer. In particular, combinations of ribociclib
Ribociclib, sold under the brand name Kisqali and Kryxana marketed by Novartis, is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of certain kinds of breast cancer. on Kisqali. Accessed 2017-09-08. Ribociclib is a kinase in ...
plus endocrine therapy have been the subject of clinical trials.
A 2019 review found moderate certainty evidence that giving people antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s before breast cancer surgery helped to prevent surgical site infection (SSI). Further study is required to determine the most effective antibiotic protocol and use in women undergoing immediate breast reconstruction.
Cryoablation
As of 2014 cryoablation
Cryoablation is a process that uses extreme cold to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive, fluids are circulated. Cryoprobes are positioned adjacent to the target in ...
is being studied to see if it could be a substitute for a lumpectomy in small cancers. There is tentative evidence in those with tumours less than 2 centimeters. It may also be used in those in who surgery is not possible. Another review states that cryoablation looks promising for early breast cancer of small size.
Breast cancer cell lines
Part of the current knowledge on breast carcinomas is based on in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
and in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
studies performed with cell lines
An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells ...
derived from breast cancers. These provide an unlimited source of homogenous self-replicating material, free of contaminating stromal
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa ...
cells, and often easily cultured in simple standard media
Media may refer to:
Communication
* Media (communication), tools used to deliver information or data
** Advertising media, various media, content, buying and placement for advertising
** Broadcast media, communications delivered over mass el ...
. The first breast cancer cell line described, BT-20, was established in 1958. Since then, and despite sustained work in this area, the number of permanent lines obtained has been strikingly low (about 100). Indeed, attempts to culture breast cancer cell lines from primary tumours have been largely unsuccessful. This poor efficiency was often due to technical difficulties associated with the extraction of viable tumour cells from their surrounding stroma. Most of the available breast cancer cell lines issued from metastatic tumours, mainly from pleural effusion
A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung.
Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...
s. Effusions provided generally large numbers of dissociated, viable tumour cells with little or no contamination by fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
and other tumour stroma cells.
Many of the currently used BCC lines were established in the late 1970s. A very few of them, namely MCF-7
MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old White woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-wor ...
, T-47D
T-47D is a human breast cancer cell line commonly used in biomedical research involving the hormonal expression of cancer cells.
Characteristics
The cells were derived from the pleural effusion of a ductal carcinoma found in the mammary gland of a ...
, MDA-MB-231
Scientists study the behaviour of isolated cells grown in the laboratory for insights into how cells function in the body in health and disease. Experiments using cell culture
Cell culture or tissue culture is the process by which cells are ...
and SK-BR-3, account for more than two-thirds of all abstracts reporting studies on mentioned breast cancer cell lines, as concluded from a Medline
MEDLINE (Medical Literature Analysis and Retrieval System Online, or MEDLARS Online) is a bibliographic database of life sciences and biomedical information. It includes bibliographic information for articles from academic journals covering medic ...
-based survey.
Molecular markers
Metabolic markers
Clinically, the most useful metabolic markers in breast cancer are the estrogen and progesterone receptors that are used to predict response to hormone therapy. New or potentially new markers for breast cancer include BRCA1 and BRCA2 to identify people at high risk of developing breast cancer, HER-2
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
, and SCD1
Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA ...
, for predicting response to therapeutic regimens, and urokinase plasminogen activator
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally i ...
, PA1-1 and SCD1
Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA ...
for assessing prognosis.
Other animals
* Mammary tumor
A mammary tumor is a neoplasm originating in the mammary gland. It is a common finding in older female dogs and cats that are not spayed, but they are found in other animals as well. The mammary glands in dogs and cats are associated with their n ...
for breast cancer in other animals
* Mouse models of breast cancer metastasis
Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be cau ...
See also
*Male breast cancer
Male breast cancer (MBC) is a cancer in males that originates in their breasts. Males account for less than 1% of new breast cancers with about 20,000 new cases being diagnosed
worldwide every year. Its incidence rates in males vs. females are, ...
*Breast Cancer Research and Treatment
''Breast Cancer Research and Treatment'' is a scientific journal focused on the treatment of and investigations in breast cancer. It is targeted towards a wide audience of clinical researchers, epidemiologists, immunologists, or cell biologists ...
, a scientific journal
References
External links
*
{{Authority control
Hereditary cancers
Human female endocrine system
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