Yes and no. Now with an indication for breast cancer prevention, tamoxifen offers new hope - but not for all, and with some risk. Other possibly safer agents are becoming available.
In 1992 the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated the first Breast Cancer Prevention Trial (BCPT) to evaluate a possible role for the drug tamoxifen in the prevention of breast cancer. In earlier studies, not only had tamoxifen been effective as adjuvant treatment during chemotherapy, but a marked decrease had been noted in the incidence of subsequent disease in the contralateral breast in patients treated with the drug, compared with those who received no adjuvant hormonal therapy. The BCPT (also known as the P-1 study) was terminated and its results published in the Journal of the National Cancer Institute in 1998. On October 29, 1998, the FDA approved the use of tamoxifen “to reduce the incidence of breast cancer in women at high risk.”
Long experience with tamoxifen, however, has shown that it does have drawbacks. The drug is considered to exhibit mixed effects, being antiestrogenic in breast tissue but estrogenic in the endometrium, bones, and liver; and a significant increase in the incidence of endometrial cancer has been consistently seen with its use. Tamoxifen is also associated with a significant increase in thromboembolic events, with Pulmonary embolism being a particular concern.
The related but more selective estrogen receptor modulator (SERM) raloxifene, as well as other SERMs such as toremifene, have also been undergoing evaluation as potentially safer alternatives to tamoxifen. The publication of a study showing a 76% decrease in breast cancer incidence among women taking raloxifene for its FDA-approved indication, osteoporosis, resulted in headlines such as “Drug slashes breast cancer risk, study shows.”
These studies of tamoxifen and raloxifene have provided the first hopeful signs of a possible pharmacologic means of preventing breast cancer. Clearly, a successful means of prophylactic intervention would be a vastly significant medical advance: 175,000 new cases of invasive breast cancer are diagnosed each year in the United States, and 44,000 women die of the disease. Despite massive research funding and intensive investigative efforts, the mortality rate for breast cancer has changed little in the past 50 years, and the small improvement that has been seen is largely a result of earlier detection methods and refinements in systemic therapy. Any progress on prevention that looks promising - even if preliminary - is certain to create intense interest among the ever-increasing number of postmenopausal women in this country and the physicians who care for them.
Use of these agents (and particularly tamoxifen; raloxifene has not been approved for use in breast cancer) now has earned a place in the hierarchy of women’s long-term health-care decisions. But authorities caution that much more information, particularly on long-term effects, will be needed before firm conclusions can be drawn and clinical recommendations made. Until such time as more long-term data become available and answers to the many remaining questions formulated, organizations such as the National Cancer Institute (NCI) are attempting to help obstetrician-gynecologists and other clinicians and their patients best evaluate the available information. The decisions must be made on a case-by-case basis, with primary attention paid to a woman’s own health-care priorities and value judgments.
By Trudy L. Bush, PhD, Steven R. Cummings, MD, and Clifford A. Hudis, MD
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