Cancer of the breast is the most common form of cancer in American women, with 178,700 new cases and 43,500 deaths estimated for 1998 (breast cancer also occurs in men, with 1,600 new cases and 400 deaths estimated for 1998). Over 80% of new cases occur in postmenopausal women. The precise cause of breast cancer is unknown. However, it is known that the earliest precancerous changes occur in the single layer of epithelial cells lining the terminal end buds (TEB) of the breast milk ductal system. Researchers have speculated that the presence of oxidized cholesterol, sex hormones, and bile acids in the TEB may bring about carcinogenic changes, but this remains to be proved.
Risk factors for breast cancer include late age of first birth, familial breast cancer, early onset of menstruation, late menopause, and, to a lesser extent, obesity. However, none of the known risk factors, alone or in combination, can account for the enormous differences in breast cancer seen worldwide. For example, compared to the United States, Japanese women have one-sixth the mortality rate for breast cancer, and in Greece the mortality rate is half. Moreover, when Japanese women move to the United States, they gradually take on the higher breast cancer rate of the United States.
These findings indicate that environmental factors are an important determinant of breast cancer risk. Researchers have studied the role of dietary fat as an environmental factor in the development of breast cancer, since Japanese dietary fat intake is significantly lower than the American intake. Animal studies indicate that high fat intake promotes the development of rat mammary tumors, but considerable controversy currently exists over this hypothesis. Studies in the United States, Canada, and the Netherlands show no increase in risk with increased fat intake. The validity of these studies is weakened by the relatively narrow window of fat intake in high-risk countries and by the biases inherent in filling out food questionnaires by memory.
Other environmental risk factors include low fiber intake and exposure to chlorinated compounds and pesticides such as PCBs (see pollutants, chemical) and DDT. Fiber appears to protect against breast cancer by either increasing the elimination of estrogens, thereby lowering the levels of estrogen in the blood, or by providing plant estrogens, which block the tumor-promoting action of estrogens. DDT and other organochlorine pesticides are of concern because they are still present in the environment and because of their ability to alter estrogen production and metabolism. Several studies have shown that elevated levels of these pesticides have been detected in breast fat and in the blood of women with breast cancer. Other studies have shown an association between blood levels of pesticides and breast cancer risk.
Breast cancer detection has focused largely on self-examination and mammography. Mammography in asymptomatic women seems to benefit primarily individuals over 40 and has led to an increase in the number of small tumors diagnosed, but it remains to be seen whether overall survival has been improved by the increase in the use of mammography. Breast cancer susceptibility genes, called BRCA-1 and BRCA-2, were discovered in the early 1990s. These mutations have been found on a specific chromosome in certain families with multiple cases of early-onset breast cancer. However, the genes appear to play no role in the 90Ð95% of breast cancer cases that occur sporadically. Early detection using DNA screening for these mutated genes have social and ethical implications that have not been fully explored, so widespread testing to detect hereditary susceptibility for breast cancer has not begun.
Traditionally, breast cancer treatment relies heavily on radiation, surgical removal of the breast, called mastectomy, and cytotoxic chemotherapy. The type of surgery depends on the extent that the cancer has invaded the surrounding tissue: a lumpectomy removes the tumor and surrounding tissues, a simple mastectomy removes the breast tissue but not the underlying muscles, and a radical mastectomy removes the breast, nearby lymph nodes, and portions of the chest and arm muscles.
Chemotherapy involving antiestrogens, such as tamoxifen, has proved useful in delaying breast cancer recurrence, but the majority of patients treated with tamoxifen eventually relapse. Similar results have been found with taxol, which prevents rapidly dividing cells from completing cell division. New approaches involving reprogramming of the tumor cell genes and targeting of the blood vessels that feed tumors provide hope for more effective and less toxic therapy. One drug under study, Herceptin, helps make chemotherapy more effective by shrinking tumors and slowing the progression of the disease. An advisory committee of the U.S. Food and Drug Administration (FDA) has recommended that Herceptin be approved for use; it will be most effective in a type of breast cancer that afflicts about 30 percent of breast cancer patients.