DESCRIPTION (provided by applicant): In the United States, more than 2 million women are living with a history of breast cancer. Because of past advances in chemotherapy, the vast majority of women diagnosed with breast cancer will survive for many years, but they will also have increased risk for long-term complications related to estrogen deficiency, lymph node dissection, and other effects of chemotherapy on health tissue Evidence suggests that women who survive breast cancer have an increased risk for osteoporosis. This risk is highest for premenopausal women who become menopausal with chemotherapy. However, controversy exists regarding the extent of bone loss, and only a few studies have evaluated mechanisms to prevent it. A double- blind randomized control trial of weekly alendronate in premenopausal women treated with adjuvant chemotherapy for breast cancer will be performed to define and compare the changes in BMD and bone turnover that occur during and after adjuvant chemotherapy for breast cancer. We expect to characterize the natural history of bone loss during chemotherapy and define risk factors that contribute to this loss in newly diagnosed premenopausal breast cancer patients. By defining factors that predict accelerated bone loss we hope to help guide preventive therapy. With the results of this trial, cost- effectiveness of bisphosphonate treatment will be modeled. We expect that bisphosphonates will significantly reduce the rate of bone loss in this patient population and that bisphosphonate use for the prevention of osteoporosis and its related complications will be cost-effective. The training portion of this proposal includes regular mentoring with Dr. Karen Antman and Dr. Elizabeth Shane; extensive interaction with Dr. Alfred Neugut, Dr. Victor Grann, and Dr. Richard Gralla; and continued formal coursework at the Mailman School of Public Health at Columbia University. My goal as an independent investigator is to conduct clinical research that will identify approaches to cancer treatment that will minimize toxic effects, prevent long- term complications, and maximize survival, quality of life, and cost- effectiveness.