In the United States each year, 170,000 women will be diagnosed with breast cancer. In primary care, age is one of the determining factors for recommending mammography because the risk for breast cancer increases with age. However, recent developments in predicting and altering breast-cancer risk justify a new view in assessing this risk in the primary care setting. Armstrong and colleagues recently discussed current methods for evaluating the risk of breast cancer and the effects of that risk on medical decisions. They also discuss the current status of hormone replacement therapy, tamoxifen and prophylactic mastectomy in women at high risk of developing breast cancer.
The lifetime risk of breast cancer for women in the United States is 12 percent (about one in eight). The longer a woman lives without breast cancer, the lower her risk of breast cancer is for the remainder of her lifetime. Thus, a 50-year-old woman who has not had breast cancer has an 11 percent chance of having breast cancer in her remaining lifetime. Four models have been developed to predict breast-cancer risk. The two most common include the Gail model (from the Breast Cancer Detection Demonstration Project) and the Claus model (from the Cancer and Steroid Hormone Study). The Gail model incorporates the number of first-degree relatives with breast cancer, age at menarche, age at first live birth (including nulliparity) and the number of breast biopsies. An individual risk score is then calculated by multiplying the relative risks from these categories by an adjusted population risk for breast cancer. The Gail model has received the most attention, with validation studies in four populations. A software program for this model is available from the National Cancer Institute (http://cancernet.nci.nih.gov/h_detect.html).
Tamoxifen is the first drug to be shown to reduce the incidence of breast cancer in healthy women, and the U.S. Food and Drug Administration (FDA) has approved labeling for this indication. In the Breast Cancer Prevention Trial, this estrogen-receptor modulator was shown to reduce the incidence of breast cancer by 49 percent compared with placebo in a study population of 13,000 women after a four-year follow-up period. Two smaller trials conducted in Europe showed no benefit from tamoxifen, but these studies have been criticized because of small study numbers, noncompliance and concurrent use of hormone replacement therapy in some of the study participants. Before prescribing tamoxifen, oncology experts recommend that women first be assessed for breast cancer risk. The Breast Cancer Prevention Trial included only women with a five-year risk of 1.7 percent. Thus, it is unclear if tamoxifen offers any benefit in normal or low-risk women. Moreover, during the prevention trial, there was a higher incidence of deep venous thrombosis (relative risk: 1.6), pulmonary emboli (relative risk: 3.0) and endometrial cancer (relative risk: 2.5). Cataract surgery was required approximately twice as often among women who took tamoxifen. The current collective opinion is that the higher a woman's risk of breast cancer, the higher the benefit of tamoxifen. For women at very high risk of breast cancer, it is believed that the benefit outweighs the adverse risks.
One recent retrospective study showed that prophylactic mastectomy reduced the risk of breast cancer by more than 90 percent in women at high risk of developing breast cancer. For a woman with an estimated lifetime risk of 40 percent (four times the population risk), surgery would add three years of life. For a woman with an estimated lifetime risk of 85 percent, prophylactic mastectomy would add more than five years to her life. However, this result must be balanced against surgical morbidity from potentially disfiguring surgery.
Two major breast cancer susceptibility genes have been identified, the BRCA1 and BRCA2 genes. Women with mutations in either of these genes have a 60 to 85 percent lifetime risk of developing breast cancer and a 15 to 40 percent risk of developing ovarian cancer. Familial characteristics that increase a woman's likelihood of carrying the BRCA mutation include early-onset breast cancer, breast and ovarian cancer and Ashkenazi Jewish ancestry (see accompanying table). Genetic screening can be used to separate women who carry one or both of these mutations from those who do not. These latter patients are at the same risk as someone without a family history of breast cancer. Genetic screening is also recommended for women in families who have risk factors for the BRCA mutation but do not have a known mutation. Physicians may want to refer such patients to a center that provides specialized genetic counseling, because these women have a significant lifetime risk (60 to 85 percent) of developing breast cancer. A list of these centers is available on the World Wide Web (http://cancernet.nci.nih.gov/genesrch.shmtl) or can be obtained by calling 1-800-422-6237.
editor's note: I encourage all family physicians to obtain a copy of the full text of this article to review because it contains critical data and information about breast cancer screening and prevention beyond the current recommendations. Simply following the established guidelines for screening mammography is no longer enough based on the issues discussed by these authors.—j.t.k.