Malignant Breast Disease

• Overview
• Risk Factors for Developing Breast Cancer
• Breast Cancer Types
• Prognostic Indicators
• Breast Cancer Staging

The American Cancer Society estimates that 182,800 new cases of invasive breast cancer will be diagnosed this year and 40.800 patients will die from the disease. Breast cancer is truly an epidemic among women and we don't know why.

Breast cancer is not exclusively a disease of women. For every 100 women with breast cancer, 1 male will develop the disease. The American Cancer society estimates that 1500 men will develop the disease this year. The evaluation of men with breast masses is similar to that in women, including mammography.

The incidence of breast cancer is very low in the twenties (age) gradually increases and plateaus at the age of forty-five and increases dramatically after fifty. Fifty percent of breast cancer is diagnosed in women over sixty-five indicating the ongoing necessity of yearly screening throughout a woman's life.

Breast cancer is considered a heterogenous disease, meaning that it is a different disease in different women, a different disease in different age groups and has different cell populations within the tumor itself. Generally, breast cancer is a much more aggressive disease in younger women. Autopsy studies show that 2% of the population has undiagnosed breast cancer at the time of death. Older women typically have much less aggressive disease than younger women.

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Risk Factors for the Development of Breast Cancer

Early onset of menses and late menopause: onset of the menstrual cycle prior to the age of 12 and menopause after 50 causes increased risk of developing breast cancer.

Diets high in saturated fat: The types of fat are important. Monounsaturated fats such as canola oil and olive oil do not appear to increase the risk of developing breast cancer like polyunsaturated fats; corn oil and meat.

Family history of breast cancer: Patients with a positive family history of breast cancer are at increased risk for developing the disease. However, 85% of women with breast cancer have a negative family history!

Family history only includes immediate relatives, mother, sisters and daughters. If a family member was post-menopausal (fifty or older) when she was diagnosed with breast cancer, the lifetime risk is only increased 5%. If the family member was premenopausal, the lifetime risk is 18.6%. If the family member was premenopausal and had bilateral breast cancer, the lifetime risk is 50%.

Women with a significantly positive family history of premenopausal breast cancer should begin screening mammography a decade sooner than their family member was diagnosed. BRCA-1 and BRCA-2 gene testing can identify those patients at increased risk, genetically, for developing not only breast cancer but also a variety of epithelial tumors including ovarian and colon cancer.

At this time genetic testing is investigational. If a woman is determined to have these genetic markers, should we recommend bilateral mastectomy and oophorectomy? Further, if her insurance company knows that she has these genetic markers of increased risk, she may loose her insurance coverage. If a woman decides to proceed with genetic testing, we recommend that this test be paid for by the individual to keep the results confidential.

Late or no pregnancies: Pregnancies prior to the age of twenty-six are somewhat protective. Nuns have a higher incidence of breast cancer.

Moderate alcohol intake: Greater than two alcoholic beverages per day.

Estrogen replacement therapy: Most studies indicate that taking estrogen longer than ten years may lead to a slight increase in risk for developing breast cancer. However, these studies indicate that the positive benefits of taking estrogen as far as reducing the risk for osteoporosis, heart disease and now more recently Alzheimer's and colon cancer, far outweigh the slight increase in risk that may be associated with estrogen replacement therapy.

Caution should be exercised in those women with a significantly positive family history of breast cancer or atypical intraductal hyperplasia. Women with breast cancer are not currently give estrogen replacement. There are no scientific studies currently justifying this practice. However, until those studies are available, by convention, women are taken off estrogen.

History of prior breast cancer: Patients with a prior history of breast cancer are at increased risk for developing breast cancer in the other breast. This risk is 1% per year or a lifetime risk of 10%. The reason for close clinical follow-up after the diagnosis of breast cancer is not only to detect recurrence of the disease, but also to detect breast cancer in the opposite breast.

Female: The mere fact that being female increases the risk of developing breast cancer. However, for every 100 women with breast cancer, 1 male will develop the disease.

Therapeutic irradiation to chest wall i.e., for Hodgkins Disease (cancer of lymph nodes): Patients who have had therapeutic irradiation to the chest are at increased risk for developing breast cancer approximately 10 years later and consideration should be given to earlier screening in this population.

Moderate obesity: The relationship of breast cancer to obesity is more complex but associated with an increased risk.

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Ductal Carcinoma in-situ: Generally divided into comedo (blackhead, the cut surface of the tumor demonstrates extrusion of dead and necrotic tumor cells similar to a blackhead) and non-comedo types. DCIS is early breast cancer confined to the inside of the ductal system. The distinction between comedo and non-comedo types is important as comedocarcinoma in-situ generally behaves more aggressively and may show areas of microinvasion (small areas of invasion through the ductal wall into surrounding tissue).

The surgical management is the same as for other types of breast cancer except axillary node sampling is not done, as only 1% of these lesions will have axillary metastasis. We recommend, however, that irradiation be given if treated with conservative breast surgery to reduce the recurrence rate from 21% without irradiation, to 5%-10% with irradiation. This is a controversial area of the treatment of breast cancer.

Infiltrating Ductal: The most common type of breast cancer representing 78% of all malignancies. These lesions can be stellate (star like in appearance on mammography) in appearance or well circumscribed (rounded). The stellate lesions generally have a poorer prognosis.

Medullary Carcinoma: Comprise 15% of breast cancers. These lesions are generally well circumscribed and may be difficult to distinguish from fibroadenoma by mammography or sonography. Medullary carcinoma is estrogen and progesterone receptor (prognostic indicator) negative 90% of the time. Medullary carcinoma usually has a better prognosis than ordinary breast cancer.

Infiltrating Lobular: Representing 15% of breast cancer these lesions generally present in the upper outer quadrant of the breast as a subtle thickening and are difficult to diagnose by mammography. Infiltrating lobular can be bilateral (involve both breasts). Microscopically, these tumors exhibit a linear array of cells (Indian filing) and grow around the ducts and lobules (targeting).

Tubular Carcinoma: Orderly or well differentiated carcinoma of the breast. These lesions make up about 2% of breast cancer. They have a favorable prognosis with nearly a 95% 10-year survival.

Mucinous Carcinoma: Represents 1%-2% of carcinoma of the breast and has a favorable prognosis. These lesions are usually well circumscribed (rounded).

Inflammatory Carcinoma: A particularly aggressive type of breast cancer the presentation is usually noted in changes in the skin of the breast including redness (erythema), thickening of the skin and prominence of the hair follicles resembling an orange peel (peau d' orange). The diagnosis is made by a skin biopsy, which reveals tumor in the lymphatic and vascular channels 50% of the time.

Inflammatory Carcinoma

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Tumor size: As the size of the tumor increases the risk of axillary and systemic metastasis increases.

Histologic Grade: the appearance of the tumor cells under the microscope and graded from 1) well differentiated, 2) Moderately differentiated and 3) poorly differentiated. The survival diminishes with increasing histologic grade.

Estrogen and Progesterone Receptors: Protein plugs on the surface of the tumor cells to which estrogen and progesterone bind. This complex moves inside the cell causing cellular division. The presence of estrogen and progesterone receptors is a good prognostic indicator. Tumors displaying these receptors will respond to hormonal manipulation, i.e., Tamoxifen.

Axillary Nodes: The most important prognostic indicator. Patients with negative axillary nodes (microscopically) have improved disease free and long-term survival.

DNA Flow Cytometry: Test that determines the genetic material within the cell. Tumors with a normal amount of DNA (diploid) have a better disease free and long-term survival than those with an abnormal amount of DNA (aneuploid). This study also determines the percentage of cells in active division. Tumors with active cellular division of < 10% have a better prognosis.

Her-2/neu: Protein product secreted by the tumor indicating a decreased disease free and long term survival.

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Staging Breast Cancer
Tumor Size or Characteristics
TX = Primary tumor cannot be assessed
TIS = Carcinoma in-situ
T0 = No evidence of primary tumor
TIS = Paget's Disease without a tumor, Carcinoma in-situ
T1 = Tumor less than 2 cm. in greatest dimension
T2 = Tumor larger than 2 cm. in size but less than 5cm.
T3 = Tumor larger than 5 cm. in size
T4 = Tumor of any size extending to the chest wall or skin

Lymph Nodes
N0 = no metastasis to axillary nodes
N1 = Metastasis to moveable axillary nodes
N2 = Metastasis to fixed or matted axillary nodes
N3 = Metastasis to supraclavicular, infraclavicular or internal mammary nodes

Metastasis
M0 = no distant metastasis
M1 = distant metastasis

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• Mammography should continue yearly after 40 throughout a woman's life.
• For every 100 women that develop breast cancer, one man will.
• 85% of women with breast cancer have a negative family history.