Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. In the year 2004, about 216,000 cases of invasive breast cancer and 40,000 deaths occurred in the United States. Epithelial malignancies of the breast are the most common cause of cancer in women (excluding skin cancer), accounting for about one-third of all cancer in women. As a result of improved treatment and earlier detection, mortality from breast cancer has begun to decrease substantially in the United States. This chapter will not consider rare malignancies of the breast, such assarcomas and lymphomas, but will focus on the epithelial cancers. Human breast cancer is a clonal disease; a single transformed cell—the product of a series of somatic (acquired) or germline mutations—is eventually able to express full malignant potential. Thus, breast cancer may exist for a long period as either a noninvasive disease or an invasive but nonmetastatic disease. These facts have very significant clinical ramifications. |
Breast cancer is a hormone-dependent disease. Women without functioning ovaries who never receive estrogen-replacement therapy do not develop breast cancer. The female to male ratio is about 150:1. For most epithelial malignancies, a log-log plot of incidence versus age shows a single-component straight-line increase with every year of life. A similar plot for breast cancer shows two components: a straight-line increase with age but with a decrease in slope beginning at the age of menopause. The three dates in a woman's life that have a major impact on breast cancer incidence are age at menarche, age at first full-term pregnancy, and age at menopause. Women who experience menarche at age 16 have only 50 to 60% of the breast cancer risk of a woman having menarche at age 12; the lower risk persists throughout life. Similarly, menopause occurring 10 years before the median age of menopause (52 years), whether natural or surgically induced, reduces lifetime breast cancer risk by about 35%. Women who have a first full-term pregnancy by age 18 have a 30 to 40% lower risk of breast cancer compared with nulliparous women. Thus, length of menstrual life—particularly the fraction occurring before first full-term pregnancy—is a substantial component of the total risk of breast cancer. These three factors (menarche, age of first full-term pregnancy, and menopause) can account for 70 to 80% of the variation in breast cancer frequency in different countries. A meta-analysis has shown that duration of maternal nursing correlates with substantial risk reduction independent of either parity or age at first full-term pregnancy. The role of diet in breast cancer etiology is controversial. While there are associative links between total caloric and fat intake and breast cancer risk, the exact role of fat in the diet is unproven. Increased caloric intake contributes to breast cancer risk in multiple ways: earlier menarche, later age at menopause, and increased postmenopausal estrogen concentrations reflecting enhanced aromatase activities in fatty tissues. Moderate alcohol intake also increases the risk by an unknown mechanism. Recommendations favoring abstinence from alcohol must be weighed against other social pressures and the possible cardioprotective effect of moderate alcohol intake. |
Because the breasts are a common site of potentially fatal malignancy inwomen and because they frequently provide clues to underlying systemic diseases in both men and women, examination of the breast is an essential part of the physical examination. Unfortunately, internists frequently do not examine breasts in men, and, in women, they are apt to defer this evaluation to gynecologists. Because of the plausible association between early detection and improved outcome, it is the duty of every physician to distinguish breast abnormalities at the earliest possible stage and to institute a definite diagnostic workup. It is for this reason that all women should be trained in breast self-examination (BSE). Although breast cancer in men is unusual, unilateral lesions should be evaluated in the same manner as in women, with the recognition that gynecomastia in men can sometimes begin unilaterally and is often asymmetric. Virtually all breast cancer is diagnosed by biopsy of a nodule detected either on a mammogram or by palpation. Algorithms have been developed to enhance the likelihood of diagnosing breast cancer and reduce the frequency of unnecessary biopsy |
A series of randomized clinical trials both in the United States and abroad have shown that breast-conserving treatments, consisting of the removal of the primary tumor by some form of lumpectomy with or without irradiating the breast, results in a survival that is as good as that after extensive procedures, such as mastectomy or modified radical mastectomy, with or without further irradiation. Postlumpectomy breast irradiation greatly reduces the risk of recurrence in the breast. While breast conservation is associated with a possibility of recurrence in the breast, 10-year survival is at least as good as that after more radical surgery. Postoperative radiation to regional nodes following mastectomy is also associated with an improvement in survival. Since radiation therapy can also reduce the rate of local or regional recurrence, it should be strongly considered following mastectomy for women with high-risk primary tumors (i.e., T2 in size, positive margins, positive nodes). At present, approximately one-third of women in the United States are managed by lumpectomy. Breast-conserving surgery is not suitable for all patients: it is not generally suitable for tumors >5 cm (or for smaller tumors if the breast is small), for tumors involving the nipple areola complex, for tumors with extensive intraductal disease involving multiple quadrants of the breast, for women with a history of collagen-vascular disease, and for women who either do not have the motivation for breast conservation or do not have convenient access to radiation therapy. However, these groups probably do not account for more than one-third of patients who are treated with mastectomy. Thus, a great many women still undergo mastectomy who could safely avoid this procedure and probably would if appropriately counseled. An extensive intraductal component is a predictor of recurrence in the breast, and so are several clinical variables. Both axillary lymph node involvement and involvement of vascular or lymphatic channels by metastatic tumor in the breast are associated with a higher risk of relapse in the breast but are not contraindications to breast-conserving treatment. When these patients are excluded, and when lumpectomy with negative tumor margins is achieved, breast conservation is associated with a recurrence rate in the breast of substantially <10%.> |
Women who have one breast cancer are at risk of developing a contralateral breast cancer at a rate of approximately 0.5% per year. When adjuvant tamoxifen is administered to these patients, the rate of development of contralateral breast cancers is reduced. In other tissues of the body, tamoxifen has estrogen-like effects that are beneficial: preservation of bone mineral density and long-term lowering of cholesterol. However, tamoxifen has estrogen-like effects on the uterus, leading to an increased risk of uterine cancer (0.75% incidence after 5 years on tamoxifen). Tamoxifen also increases the risk of cataract formation. The Breast Cancer Prevention Trial (BCPT) revealed a >49% reduction in breast cancer among women with a risk of at least 1.66% taking the drug for 5 years. Raloxifene has shown similar breast cancer prevention potency but may have different effects on bone and heart. The two agents are being compared in a prospective randomized prevention trial (the STAR trial). |
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