Invasive carcinoma of no special type (NST) also known as invasive ductal carcinoma or ductal NOS and previously known as invasive ductal carcinoma, not otherwise specified (NOS) is a group of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

s that do not have the "specific differentiating features". Those that have these features belong to other types. While breast cancer is extremely rare in men, invasive carcinoma of no special type is the most commonly diagnosed form of

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, ...

. In this group are: pleomorphic carcinoma, carcinoma with osteoclast-like stromal giant cells, carcinoma with choriocarcinomatous features, and carcinoma with melanotic features. It is a diagnosis of exclusion, which means that for the diagnosis to be made all the other specific types must be ruled out.

Classification

Invasive carcinoma of no special type (NST) is the most common form of invasive breast cancer. It accounts for 55% of breast cancer incidence upon diagnosis, according to statistics from the United States in 2004.Percentage values are from United States statistics 2004. Subtype specific incidences are taken fro
Table 6
(invasive) an

(in situ) from . These are divided by total breast cancer incidence (211,300 invasive and 55,700 in situ cases) as reported from Breast Cancer Facts & Figures 2003-2004 It is also the most common form of breast cancer occurring in men. On a

mammogram Mammography (also called mastography) is the process of using low-energy X-rays (usually around 30 Peak kilovoltage, kVp) to examine the human breast for diagnosis and screening. The goal of mammography is the early detection of breast cancer, ty ...

, it is usually visualized as a mass with fine spikes radiating from the edges. On

physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the pati ...

, this lump usually feels much harder or firmer than benign breast lesions such as

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 glandula ...

. On microscopic examination, the cancerous cells invade and replace the surrounding normal tissues. IDC is divided in several

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 ...

subtypes.

Signs and symptoms

In many cases, ductal carcinoma is asymptomatic, and detected as abnormal results on mammography. When symptoms occur, a painless, enlarging mass that does not fluctuate with the

menstrual period The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs ...

may be felt. Pinching of the overlying skin may also be seen. Certain subtypes, such as inflammatory carcinomas, may result in a swollen, enlarged and tender breast. All variants of cancer, if there is metastatic spread, may cause enlarged

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 inclu ...

and affect other organs.

Causes

The cancer may form from the precancerous lesion called

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 ...

Diagnosis

Tumor size

Tumors under 1 cm in diameter are unlikely to spread systemically. Tumors are staged by size.

Lymph node involvement

Absence of cancer cells in the lymph nodes is a good indication that the cancer has not spread systemically. Presence of cancer in the lymph nodes indicates the cancer may have spread. In studies, some women have had presence of cancer in the lymph nodes, were not treated with chemotherapy, and still did not have a systemic spread. Therefore, lymph node involvement is not a positive predictor of spread.

Clinical staging

Tumor size staging and node involvement staging can be combined into a single clinical staging number.

Histopathologic criteria

Carcinomatous cells are seen below the basement membrane of

lactiferous 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. Otherwise, there are no specific histologic characteristics, essentially making it a diagnosis of exclusion. Image:Muc1.jpg, Invasive ductal carcinoma of the breast assayed with anti Mucin 1 antibody. Image:HER2(2).jpg, Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody. Image:Breast invasive scirrhous carcinoma histopathology (1).jpg, Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. Hematoxylin and eosin stain. Image:IDC1.jpg, Invasive ductal carcinoma of the breast. H&E stain. Image:Breast invasive scirrhous carcinoma histopathology (2) HER2 expression.JPG, Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. HER-2/neu oncoprotein expression by Ventana immunostaining system. Image:H&E 10x Invasive ductal.jpg, Histopathology of invasive ductal carcinoma of the breast. H&E stain. File:Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg, Invasive ductal carcinoma, with occasional entrapped normal ducts (arrow)

Grading

The appearance of cancer cells under a microscope is another predictor of systemic spread. The more different the cancer cells look compared to normal duct cells, the greater the risk of systemic spread. There are three characteristics that differentiate cancer cells from normal cells. # Tendency to form tubular structures # Nuclear size, shape, and staining intensity # Mitotic rate - Rate of cell division The histologic appearance of cancer cells can be scored on these three parameters on a scale from one to three. The sum of these grades is a number between 3 and 9. The score is called a Bloom Richardson Grade (BR) and is expressed um of the grades9. For example, cells that were graded 2 on all three parameters would result in a BR score of 6/9. A score of 5 and under is considered low. 6 to 7 is considered intermediate. 8 to 9 is considered high.

Vascular invasion

The presence of cancer cells in small blood vessels is called vascular invasion. The presence of vascular invasion increases the probability of systemic spread.

DNA analysis

DNA analysis indicates the amount of DNA in cancer cells and how fast the cancer is growing. Cells with the normal amount of DNA are called diploid. Cells with too much or too little DNA are called aneuploid. Aneuploid cells are more likely to spread than diploid cells. DNA testing indicates the rate of growth by determining the number of cells in the synthetic phase (S Phase). An S Phase > 10% means a higher chance of spreading. The results of DNA testing are considered less reliable predictors of spread than size, histology, and lymph node involvement.

Prognosis

According to the NIH Consensus Conference, if DCIS is allowed to go untreated, the natural course or natural history varies according to the grade of the DCIS. Unless treated, approximately 60 percent of low-grade DCIS lesions will have become invasive at 40 years' follow-up. High-grade DCIS lesions that have been inadequately resected and not given radiotherapy have a 50 percent risk of becoming invasive breast cancer within seven years. Approximately half of low-grade DCIS detected at screening will represent overdiagnosis, but overdiagnosis of high-grade DCIS is rare. The natural history of intermediate-grade DCIS is difficult to predict. Approximately one-third of malignant calcification clusters detected at screening mammography already have an invasive focus. The prognosis of IDC depends, in part, on its histological subtype. Mucinous, papillary, cribriform, and tubular carcinomas have longer survival, and lower recurrence rates. The prognosis of the most common form of IDC, called "IDC Not Otherwise Specified", is intermediate. Finally, some rare forms of breast cancer (e.g., sarcomatoid carcinoma, inflammatory carcinoma) have a poor prognosis. Regardless of the histological subtype, the prognosis of IDC depends also on tumor size, presence of cancer in the lymph nodes,

histological grade In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms (cancer); others apply also to benign neoplasms. The neoplastic grading is a measure of cell ...

, presence of cancer in small vessels (vascular invasion), expression of

hormone receptors A hormone receptor is a receptor molecule that binds to a specific chemical messenger . Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptor ...

and of

oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

HER2/neu 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 ...

. These parameters can be entered into models that provide a statistical probability of systemic spread. The probability of systemic spread is a key factor in determining whether radiation and chemotherapy are worthwhile. The individual parameters are important also because they can predict how well a cancer will respond to specific chemotherapy agents. Overall, the five-year survival rate of invasive ductal carcinoma was approximately 85% in 2003.''NOTE: Article really refers to invasive ductal carcinoma, despite title.''

Treatment

Treatment of invasive carcinoma of no special type (NST) depends on the size of the mass (size of the tumor measured in its longest direction): * <4 cm mass: surgery to remove the main tumor mass and to sample the

in the axilla. 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 tumor is ascertained after this first surgery. Adjuvant therapy (i.e., treatment after surgery) may include a combination of

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. Chemothe ...

, radiotherapy, hormonal therapy (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/or targeted therapy (e.g.,

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 wi ...

). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences. * 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the

in the axilla. The treatment options offered to an individual patient are determined by the form, stage and location of the cancer, and also by the age, history of prior disease and general health of the patient. Not all patients are treated the same way.

References

External links

Infiltrating Ductal Carcinoma
{{Breast cancer types Breast cancer