Adjuvant chemotherapy reduces mortality rates in women with breast cancer. Because many breast cancer patients have prolonged survival after adjuvant treatment the long term health effects associated with adjuvant chemotherapy are important to evaluate. Premature ovarian failure (menopause) occurs in approximately 70% of premenopausal breast cancer patients who receive adjuvant chemotherapy. The resulting estrogen deficiency and premature menopause in women with breast cancer may result in accelerated loss of bone, and the risk for subsequent skeletal fractures (osteoporosis). To investigate whether breast cancer patients who develop chemotherapy-induced premature ovarian failure experience accelerated bone loss, in Specific Aim #1 we will prospectively examine bone mineral density and biochemical indices of skeletal homeostasis in premenopausal breast cancer patients who develop chemotherapy-induced premature ovarian failure.
In Specific Aim #2 we will test whether nasal spray calcitonin, an inhibitor of bone resorption, prevents bone loss in these women. Premenopausal breast cancer patients with 0-3 axillary nodal metastases will be recruited to participate in this research study. One-hundred such women will undergo baseline evaluations of menstrual status, follicle-stimulating hormone (FSH), estradiol (E2), and progesterone, (P), reproductive history questionnaire, activity questionnaire, self-rating depression questionnaire, 3-day dietary evaluation, quantitative measurements of bone mineral density of the lumbar spine and proximal femur, and biochemical indices of skeletal homeostasis (serum ionized calcium, parathyroid hormone, and osteocalcin). (DEXA) method. Following the baseline evaluation adjuvant chemotherapy will be administered. The baseline measurements will then be repeated at 6, 12, and 24 months. At the 12 month evaluation women with chemotherapy-induced ovarian failure (approximately 70% of participants) will be randomly allocated to either one year of nasal spray calcitonin (200 IU/day) plus 1500 mg of oral daily calcium intake or nasal spray placebo plus 1500 mg of oral daily calcium intake in a double-blind placebo-controlled trial. Tamoxifen may also prevent bone loss and inhibit bone resorption.
In Specific Aim #3 we will test whether tamoxifen prevents bone loss in breast cancer patients with chemotherapy-induced ovarian failure. In this observational study 42 premenopausal breast cancer patients with 0-3 axillary nodal metastases who receive adjuvant chemotherapy and tamoxifen will undergo the baseline evaluation and study evaluations at 6, 12, and 24 months. These prospective studies in premenopausal women with breast cancer will provide insights into the natural history of chemotherapy- induced ovarian failure and bone loss, and the effects of nasal spray calcitonin and tamoxifen in preventing the accelerated bone loss in these women.
