Breast Cancer - cancer that originates in the breast. Breast cancer is the second leading cause of cancer death in women (following lung cancer). Even allowing for improvements in detection (i.e., the introduction of routine mammography), there has been a long-term gradual increase in the incidence of breast cancer since the early 1970s, but because of the more effective treatment afforded by such early detection, overall mortality began to decrease by the mid-1990s. Breast cancers can arise in the lobes or lobules (lobular carcinoma) or in the ducts (ductal carcinoma) of the breast. Lobular carcinoma often affects both breasts.

Causes

Epidemiological study has identified certain risk factors that increase the possibility that a woman will get breast cancer, although not all women with breast cancer have these traits, and many women with all of these traits do not develop the disease. Risk factors include age (the incidence of breast cancer is rare in women under 35—most cases occur in women over 60); a history of breast cancer in a close blood relative; and a history of breast cancer or benign proliferative breast disease. A high cumulative exposure to female sex hormones (estrogen and progesterone) appears to increase the risk of some breast cancers. Hormonally related risk factors include early menarch (before age 12), late menopause (after age 55), having no children or postponing childbirth, and obesity in women over 50. Many other possible associations are under study, such as those relating to postmenopausal estrogen replacement, alcohol and fat consumption, lack of exercise, and exposure to pesticides and other environmental chemicals. Tumors in women of African descent are known to be particularly aggressive.

Like all cancers, breast cancers result from changes in the structure or function of genes that are key to the regulation of cellular growth, differentiation, or repair. Acquired changes in a number of specific genes have been associated with the disease; these are changes that occur during a person's lifetime but are not inherited or passed on. About 5% of women with breast cancer have an inherited susceptibility to the disease, and most of these women have an inherited mutation in one of two genes. In 1994 it was discovered that women who inherit a mutated BRCA1 gene have an almost 85% chance of developing breast cancer and an increased chance of developing uterine cancer. BRCA1 normally acts to prevent tumors by repairing damage to the genetic material caused by oxidation, a chemical process that in the body occurs naturally during metabolism. Defective BRCA1 genes cannot repair this damage, allowing its effects to accumulate over time. Cells with oxidative damage to the genes that control their growth can proliferate, or become cancerous. The defective gene can be inherited from either parent, but appears to cause breast cancer only in women. Young women who get breast cancer often come from families that carry a BRCA1 mutation. BRCA1 mutations account for about half of known hereditary breast cancers. Another gene, named BRCA2, has also been identified. BRCA2 mutations have been associated with both female and rare male breast cancers. The two genes may also play a role in some ovarian cancers and sporadic (nonhereditary) breast cancer cases.

Early Detection and Prevention

Monthly breast self-examination and regular mammography are the recommended methods of breast cancer early detection. The first sign of breast cancer may be a lump in the breast; a thickening, swelling, or dimpling; skin irritation or scaliness; pain; or a discharge or tenderness of the nipple. A biopsy can rule out or confirm a malignancy. A major recent study has shown that the drug tamoxifen can prevent breast cancer in women considered at high risk of developing the disease.

Treatment

In most cases, treatment for breast cancer begins with surgical excision of the tumor. Modern treatment attempts to preserve as much tissue as possible for both functional and cosmetic reasons. This may mean a lumpectomy (simple excision of only the cancerous tumor) or mastectomy (excision of part or all of the breast tissue, sometimes with adjacent muscle). The lymph nodes under the arm are often excised in a procedure known as an axillary dissection. In some cases, chemotherapy and external beam radiation therapy or radioactive isotopes implanted directly into the area of the cancer, are used in addition to or instead of surgery. Hormone therapy in the form of ovary removal or a drug such as tamoxifen or anastrozole is sometimes used to slow the growth of or prevent recurrence of hormonally sensitive tumors. Bone marrow transplantation is sometimes used when bone marrow that has been destroyed by large doses of chemotherapy or radiation therapy needs to be replaced.

Many women who have had a mastectomy decide to have breast reconstruction surgery. This reconstruction is done with breast implants or the patient's own tissue. Due to the controversy over silicone implants, saline-filled implants are usually used today. Women who have had an axillary dissection often experience chronic, progressive pain, numbness, and weakness in the affected arm. Lymphedema, painful swelling of the arm, can occur after node dissection or radiation treatment of the lymph nodes.

Bibliography

See Y. Hirshaut and P. I. Pressman, Breast Cancer: The Complete Guide (3d ed. 2000). See also publications of the National Cancer Institute, the American Cancer Society, the National Breast Cancer Association, and the National Lymphedema Network.

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