Adjuvant therapy with the selective estrogen receptor modulator tamoxifen helps some women with early-stage breast cancer reduce their risk of recurrence. But some studies have suggested this benefit levels off after 5 years, and further treatment with tamoxifen not only doesn't help, it may increase a woman's risk of endometrial cancer.
To get around this, researchers have suggested following a 5-year tamoxifen treatment with the SERM raloxifene, a drug used to prevent osteoporosis in postmenopausal women. Results from a large randomized clinical trial of raloxifene suggested that the drug may decrease a woman's risk of breast cancer without increasing her risk of endometrial cancer.
However, the new study suggests that raloxifene after tamoxifen may not be beneficial. O'Regan and her colleagues exposed breast and endometrial tumors in mice to combinations of estrogen, tamoxifen, and raloxifene or nothing at all. The authors found that raloxifene did not further prevent the growth of breast tumors previously exposed to more than 5 years of tamoxifen. Furthermore, raloxifene did not block the growth of endometrial tumors caused by low-dose estrogen. The authors conclude that treatment with raloxifene after 5 years of tamoxifen treatments may not further decrease breast cancer recurrence and may increase the incidence of endometrial cancer.
These findings "do not support an optimistic future for the use of raloxifene as a replacement for tamoxifen after 5 years of adjuvant therapy," says Michael B. Sporn, M.D., of Dartmouth Medical School, in an editorial. However, he points out that the current study does not address whether raloxifene might be useful in preventing the development of a second primary breast cancer or a primary endometrial cancer.
Sporn noted that the Study of Tamoxifen and Raloxifene, a large randomized clinical trial, will test the efficacy of raloxifene and tamoxifen on the primary prevention of breast cancer and endometrial cancer in high-risk women.
Contact: Elizabeth Crown, Northwestern University Medical School, (312) 503-8928, fax: (312) 503-6743, e-crown@northwestern.edu
Editorial: Hali Wickner, Dartmouth Medical School, (603) 650-1492; fax: (603) 650-1730, DMS.communications@dartmouth.edu
O'Regan RM, Gajdos C, Dardes RC, De Los Reyes A, Park W, Rademaker AW, Jordan VC. Effects of raloxifene after tamoxifen on breast and endometrial tumor growth in athymic mice. J Natl Cancer Inst 2002;94:274–83.
Editorial: Sporn MB. Hobson's choice and the need for combinations of new agents for the prevention and treatment of breast cancer. J Natl Cancer Inst 2002;94:242–3.
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JNCI Journal of the National Cancer Institute