Women with a history of breast cancer have an increased risk of developing cancer in the opposite breast. This risk increases in women who have a family history of breast cancer and in premenopausal women. Treating women who have breast cancer with tamoxifen significantly reduces the incidence of contralateral breast cancer compared with the incidence in women who did not undergo tamoxifen treatment. The reduction in incidence of contralateral breast cancer is proportional to the length of tamoxifen treatment. Adjuvant chemotherapy trials in breast cancer have not demonstrated a significant reduction in the incidence of contralateral breast cancer.

O'Regan and associates reviewed the available data on tamoxifen and contralateral breast cancer in an attempt to classify secondary neoplasms. Prospective, randomized tamoxifen trials were reviewed. Tamoxifen significantly reduced the incidence of contralateral breast cancer, and its antiestrogen effect seemed to slow the development and growth of breast cancer, which is primarily governed by the direct action of estrogen. The greatest reduction was observed in postmenopausal women and women with axillary node–positive cancers. Some trials have shown that contralateral breast cancers in women who were treated with tamoxifen were more frequently estrogen-receptor–negative, compared with primary tumors and contralateral breast cancers in women who were not treated with tamoxifen. This result is expected because tamoxifen presumably controls the estrogen-receptor–positive cancer cells. Studies demonstrate no significant difference in outcome after diagnosis of contralateral breast cancer between the tamoxifen-treated and control groups.

The use of tamoxifen appears to be safe, with occasional vasomotor symptoms and a small increase in the incidence of thromboembolic phenomena, cataracts and uterine cancer. Although tamoxifen exhibits anti-estrogen effects in the breast, its use does not significantly reduce bone density or increase the risk of coronary heart disease.

The authors conclude that tamoxifen treatment significantly reduces the incidence of contralateral breast cancer in women. A longer duration of treatment also produces a greater reduction in incidence. Preliminary data demonstrate a reduction in the incidence of invasive breast cancer in women at high risk of developing breast cancer who were treated with tamoxifen, compared with women who received placebo.

In an editorial in the same journal, Kinne points out that the benefits of tamoxifen are less certain in premenopausal women and women with positive nodes. He notes that the impact on survival rate is also less certain. Risk evaluation for the use of tamoxifen should be individualized, because patients who have undergone hysterectomy and are not at risk for thromboembolic problems will have the least negative effects from tamoxifen treatment. The use of prophylactic contralateral mastectomy is another option that should be considered in appropriate patients.

editor's note: The use of selective estrogen receptor modulators is demonstrating more promise in the prevention of breast cancer. Cummings and associates noted that the risk of invasive breast cancer in postmenopausal women with osteoporosis was significantly reduced during three years of raloxifene treatment. Because raloxifene seems to be more associated with a decreased risk of endometrial cancer than estrogen or tamoxifen (Cummings SR, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women. Results from the MORE randomized trial. JAMA June 16, 1999;281:2189–97), we can be hopeful that further research with this class of pharmacologics will provide a strong and safe tool for prevention of several of the medical problems of postmenopausal women.—r.s.