Mammary ductal carcinoma





Mammary ductal carcinoma is the most common type of breast cancer in women. It comes in two forms: invasive ductal carcinoma (IDC), an infiltrating, malignant and abnormal proliferation of neoplastic cells in the breast tissue, or ductal carcinoma in situ (DCIS), a noninvasive, potentially malignant, neoplasm that is still confined to the milk ducts (lactiferous ducts), where breast cancer most often originates.

Invasive ductal carcinoma
Invasive ductal carcinoma (IDC) 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. On a mammogram, it is usually visualized as a mass with fine spikes radiating from the edges. On physical examination, this lump usually feels much harder or firmer than benign breast lesions such as fibroadenoma. On microscopic examination, the cancerous cells invade and replace the surrounding normal tissues. IDC is divided in several histological subtypes.

Prognosis for IDC
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, presence of cancer in small vessels (vascular invasion), expression of hormone receptors and of oncogenes like HER2/neu.

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 5-year survival rate of invasive ductal carcinoma was approximately 85% in 2003.

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.

Histologic appearance
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.
 * 1) Tendency to form tubular structures
 * 2) Nuclear size, shape, and staining intensity
 * 3) 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 [sum of the grades]/9. 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 cell 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 testings 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.

Treatment options for IDC
Treatment of IDC 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 lymph nodes in the axilla. The stage of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e. treatment after surgery) may include a combination of chemotherapy, radiotherapy, hormonal therapy (e.g. tamoxifen) and/or targeted therapy (e.g. trastuzumab). 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 lymph nodes 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.

Ductal carcinoma in situ (intraductal carcinoma)
Ductal carcinoma in situ (DCIS, also known as intraductal carcinoma) is the most common type of noninvasive breast cancer or pre-cancer in women. Ductal carcinoma refers to the development of cancer cells within the milk ducts of the breast. In situ means "in place" and refers to the fact that the cancer has not moved out of the duct and into any surrounding tissue.

Ductal carcinoma in situ (DCIS) is noninvasive breast cancer that encompasses a wide spectrum of diseases ranging from low-grade lesions that are not life threatening to high-grade lesions that may harbor foci of invasive breast cancer. DCIS has been classified according to architectural pattern (solid, cribriform, papillary, and micropapillary), tumor grade (high, intermediate, and low grade), and the presence or absence of comedo histology.

DCIS almost never produces symptoms or a lump that can be felt, so it is almost always found through screening mammography. As screening mammography has become more widespread, DCIS has become one of the most commonly diagnosed breast conditions, now accounting for 20% of breast cancers and pre-cancers that are detected through screening mammography. DCIS is usually seen on a mammogram as very small specks of calcium known as microcalcifications. However, not all microcalcifications indicate the presence of DCIS, which must be confirmed by biopsy.

Treatment options for DCIS
Surgical excision, aimed at excising all of the abnormal duct elements, is a common treatment, and radiation after surgery further reduces the risk that the DCIS will recur.

DCIS patients have two surgery strategy choices: They are lumpectomy (most commonly followed by radiation therapy) or mastectomy. The survival rate is equally high for both treatments, 96 percent or higher.

Women also have the option of rejecting surgery. The survival rate here is unknown. Women who reject surgery tend to be older or have other, serious health problems, which further complicates comparisons.

Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer.

Adjunct radiotherapy after lumpectomy offers equivalent survival to mastectomy, although there is a slightly higher risk of recurrence of DCIS or invasive breast cancer. The addition of radiation therapy to lumpectomy reduces the risk of local recurrence to approximately 12 percent, of which approximately half will be DCIS and half will be invasive breast cancer; the risk of recurrence is 1 percent for women undergoing mastectomy. In addition, radiation therapy may reduce recurrence among patients with DCIS getting breast-conserving surgery (lumpectomy) as compared to breast-conserving surgery alone according to a systematic review. Patients who received breast-conserving surgery plus radiation therapy had a lower DCIS recurrence rate than patients who received breast conserving surgery alone. The use of radiation therapy did not have an effect on mortality.

Black women with DCIS have higher risks of local recurrence of DCIS or invasive breast cancer than white women. Extensive DCIS of high grade, large size, and resected with minimal surgical margins, even with radiotherapy, also have a higher risk of recurrence.

Because of the higher risk of recurrence, mastectomy may be the preferred treatment for some women or in certain instances e.g. if:
 * DCIS is "multi-focal" (present in two or more areas of the breast).
 * The DCIS tumor is relatively large or of high grade.
 * Failure to achieve adequate margins on attempted lumpectomy.
 * The breast has previously received radiation treatment.
 * The patient has had scleroderma or another disease of the connective tissue, which can complicate radiation treatment.
 * The patient lives in an area where radiation treatment is inaccessible or inconvenient.
 * The patient is under the age of 40.

A system for analyzing the suitability of DCIS patients for the options of breast conservation without radiation, breast conservation with radiation, or mastectomy is called the Van Nuys Prognostic Scoring Index (VNPI). This VNPI analyzes DCIS features in terms of size, grade, surgical margins, and patient age and assigns "scores" to favorable features.

Tamoxifen or another hormonal therapy is recommended for some women with estrogen-receptor positive DCIS to help prevent invasive breast cancer. Hormonal therapy further decreases the risk of recurrence of DCIS or the development of invasive breast cancer. However, hormone treatment increases the risk of endometrial cancer, severe circulatory problems, or stroke. In addition, hot flashes, vaginal dryness, abnormal vaginal bleeding, and a possibility of premature menopause are common for pre-menopausal women who start treatment.

Unlike women with invasive breast cancer, most women with DCIS do not undergo chemotherapy as it is usually completely removed by surgery. Some institutional series reporting significant rates of recurrent invasive cancers after mastectomy for DCIS have recently endorsed routine sentinel node biopsy (SNB) in these patients, while others have concluded it be reserved for selected patients. Most agree that SNB should be considered with tissue diagnosis of high risk DCIS (grade III with palpable mass or larger size on imaging) as well as in patients undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS. Experts are not sure whether all women with DCIS would eventually develop invasive breast cancer if they live long enough without undergoing treatment.

Dr. Diana Zuckerman and colleagues at the Cancer Prevention and Treatment Fund created a free patient booklet to guide DCIS patients on choosing the best treatment option for them.

Natural history and 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 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.