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Managing the Risk of Osteoporosis in Women With a History of Early Breast Cancer

Managing the Risk of Osteoporosis in Women With a History of Early Breast Cancer

This excellent and practical article by Dr. Ravdin is worthwhile reading for every physician involved in the long-term care of women with a previous diagnosis of breast cancer. Dr. Ravdin clearly outlines the theoretical rationale underlying the increased risk of osteopenia and osteoporosis in women with a history of breast cancer. The fact that such women commonly undergo premature menopause either deliberately, as part of treatment for breast cancer, or as a secondary effect of chemotherapy, and that estrogen-replacement therapy with or without progesterone remains contraindicated for fear of increasing the risk of recurrence, clearly contributes to the increased possibility of developing osteopenia or osteoporosis. New data supporting the role of aromatase inhibitors in adjuvant therapy[1-4] will undoubtedly lead to the increased use of these agents in the adjuvant therapy of breast cancer, with the probability of increasing the risk of decreased bone density. Underestimate of Risk
It seems clear from the adjuvant studies of aromatase inhibitors cited above that there may well be an increased incidence of osteopenia, osteoporosis, and/or fractures associated with even the short-term use of these agents in adjuvant therapy. The Arimidex, Tamoxifen Alone or in Combination (ATAC) trial reports an increased incidence of fracture, while the Canadian- led MA.17 study and the Intergroup Exemestane Study (IES) report marginally increased self-reported or physician-elicited incidences of osteoporosis and/or fracture. Since osteoporosis develops gradually over several years and fractures may be asymptomatic- or, if symptomatic, are often seen only 5 to 10 years or more into the natural history of this disease- reports from studies with a median follow- up of 3 to 5 years likely represent an underestimate of the risk of fracture in women receiving this therapy. Thus, Dr. Ravdin's succinct summary of a practical approach to such patients is both timely and useful. In truth, however, there is little evidence demonstrating that the use of approaches that are effective in osteoporosis in general are equally effective in women with a prior diagnosis of breast cancer. Theoretically, it would seem that these approaches should work in a similar fashion, but few studies have been conducted in these women up to the present time. Ongoing Trials
Currently, several ongoing trials are exploring the role of zoledronic acid (Zometa) in women receiving anastrozole (Arimidex), and of other bisphosphonates in women receiving exemestane (Aromasin). Specific results of such trials are not as yet available. Hopefully, these powerful bisphosphonates will work as well in such women as they have been shown to do in osteoporotic and osteopenic women without a history of breast cancer. In the meantime, Dr. Ravdin's article will provide a scientifically based and practical approach to the management of this situation in postmenopausal women with the diagnosis of breast cancer.

Disclosures

Dr. Pritchard is a consultant for Aventis, AstraZeneca, Roche, Pharmacia Inc, Ortho-Biotech, Pfizer, YM Bioscience, and Biomira; has received research funding from and/or through the National Cancer Institute of Canada Clinical Trials Group, Pharmacia Inc, AstraZeneca, Bristol Myers Squibb, Aventis, Amgen, Ortho-Biotech, and Pfizer; has given paid expert testimony for Aventis and AstraZeneca; and has been an advisory committee member for Aventis, AstraZeneca, Ortho-Biotech, Roche, and Pharmacia Inc.

References

1. The ATAC Trialists Group: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomized trial. Lancet 359:2131-2139, 2002.
2. The ATAC Trialists Group: Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: Results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) Trial efficacy and safety update analyses. Cancer 98:1802-1810, 2003.
3. Goss PE, Ingle JN, Martino S, et al: A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793-1802, 2003.
4. Coombes RC, Hall E, Gibson L, et al: A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 350:1081-1091, 2004.
 
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