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Caring for the Breast Cancer Survivor

      To the Editor:
      We read with interest the nice review, “Caring for the breast cancer survivor,” by Chalasani et al in the Journal.
      • Chalasani P.
      • Downey L.
      • Stopeck A.T.
      Caring for the breast cancer survivor: a guide for primary care physicians.
      The effect of tamoxifen use on bone health in breast cancer survivors needs further clarification.
      Tamoxifen is an effective and widely used treatment for primary breast cancer in both pre- and postmenopausal women. Although it has a positive effect on the bones of postmenopausal women, its effect on premenopausal women is a negative one; a fact the authors failed to state.
      Tamoxifen's negative effect on the bone was demonstrated in several clinical studies. In one trial, bone mineral density (BMD) was measured in 179 premenopausal and postmenopausal healthy women who participated in a placebo-controlled tamoxifen chemoprevention trial. In the premenopausal women, BMD decreased progressively in the lumbar spine (P <.001) and in the hip (P <.05) for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar BMD in tamoxifen-treated women who remained premenopausal throughout the study period was 1.88%, compared with a small gain of 0.24% for women on placebo (P <.001). Tamoxifen had the opposite effect in postmenopausal women; the mean annual increase in BMD for women on tamoxifen was 1.17% in the spine (P <.005) and 1.71% in the hip (P <.001), compared with no significant loss in the placebo group.
      • Powles T.J.
      • Hickish T.
      • Kanis J.A.
      • Tidy A.
      • Ashley S.
      Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women.
      In a more recent trial, 111 premenopausal women with early breast cancer were treated with adjuvant chemotherapy. Following the completion of chemotherapy, patients with hormone receptor-positive tumors were given tamoxifen, while those with hormone receptor-negative tumors received no further therapy (control group). A significant bone loss (P <.0001) was noted in tamoxifen-treated patients who continued to menstruate after chemotherapy. At 3 years of follow-up, menstruating patients on tamoxifen had lost 4.6% of their baseline BMD values, while a modest gain of 0.6% was noted in the control group.
      • Vehmanen L.
      • Elomaa I.
      • Blomqvist C.
      • Saarto T.
      Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status.
      Lastly, the study that the authors cited in their article when addressing this issue and that showed a positive tamoxifen effect on the bone, was on women who were 50 years of age or older and did not include any premenopausal women.
      • Cooke A.L.
      • Metge C.
      • Lix L.
      • Prior H.J.
      • Leslie W.D.
      Tamoxifen use and osteoporotic fracture risk: a population-based analysis.
      In conclusion, tamoxifen treatment is associated with a significant loss of BMD in premenopausal women, whereas it prevents bone loss in postmenopausal women. These adverse and beneficial effects of tamoxifen on the bone should be considered in following-up such patients in a primary care setting.

      References

        • Chalasani P.
        • Downey L.
        • Stopeck A.T.
        Caring for the breast cancer survivor: a guide for primary care physicians.
        Am J Med. 2010; 123: 489-495
        • Powles T.J.
        • Hickish T.
        • Kanis J.A.
        • Tidy A.
        • Ashley S.
        Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women.
        J Clin Oncol. 1996; 14: 78-84
        • Vehmanen L.
        • Elomaa I.
        • Blomqvist C.
        • Saarto T.
        Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status.
        J Clin Oncol. 2006; 24: 675-680
        • Cooke A.L.
        • Metge C.
        • Lix L.
        • Prior H.J.
        • Leslie W.D.
        Tamoxifen use and osteoporotic fracture risk: a population-based analysis.
        J Clin Oncol. 2008; 26: 5227-5232

      Linked Article

      • Caring for the Breast Cancer Survivor: A Guide for Primary Care Physicians
        The American Journal of MedicineVol. 123Issue 6
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          Breast cancer accounts for more than 25% of cancers in women. Because of improved screening and treatment modalities, mortality has decreased significantly. Currently, over 2.5 million breast cancer survivors live in the US and receive care from a primary care provider. Providers need to be aware of common and serious complications of breast cancer treatment. In this review we discuss complications of local and systemic treatment for breast cancer, including lymphedema, osteoporosis, cardiovascular disease, and vasomotor symptoms.
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      • The Reply
        The American Journal of MedicineVol. 124Issue 2
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          We appreciate Abdel-Razeq's comments on our review Caring for the Breast Cancer Survivor1 and agree with his comment that tamoxifen's effects on bone mineral density vary with the menopausal status of the patient. Tamoxifen does cause bone loss in women who continue to have active menstrual cycles. However, for the majority of premenopausal women with breast cancer, treatment with chemotherapy results in amenorrhea. Thus, when they subsequently start their adjuvant hormonal treatment with tamoxifen, they are in effect postmenopausal.
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