Predictors of Ovarian Function in Women Treated With Aromatase Inhibitors

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DESCRIPTION (provided by applicant): The purpose of this K07application is to provide the necessary training and environment to prepare the candidate to become an independent investigator, able to design, conduct, and acquire funding for high-quality clinical and translational studies that focus on endocrine therapy for breast cancer. During the proposed mentored period, career development activities will include (1) completion of a Masters Degree in Clinical Research Design and Statistical Analysis (K30 program), as well as additional didactic instruction in genetics, pharmacogenomics, and the ethics of genomic research, (2) mentorship by Dr. Daniel Hayes (an internationally recognized expert in breast cancer treatment and tumor marker analysis) in the design, execution, and interpretation of studies related to predictors of ovarian function during adjuvant aromatase inhibitor(AI) therapy for breast cancer, and (3) substantial collaboration with senior colleagues in the Consortium on Breast Cancer Pharmacogenomics and at the University of Michigan on pharmacogenomics, ovarian reserve, and the menopausal transition. The candidate proposes a research project that will focus on premenopausal women with early stage breast cancer who develop chemotherapy-induced ovarian failure (CIOF). These women likely would derive more benefit from estrogen deprivation with AI therapy than from tamoxifen, as has been demonstrated for postmenopausal women. However, a substantial percentage is likely to recover ovarian function during AI therapy due to LHRH feedback loops, which would render AI therapy ineffective. The cornerstone of this proposal is a prospective clinical trial of AI therapy in women with CIOF. The overall goal is to identify clinically applicable genetic, epidemiologic, and biochemical predictors of alterations of ovarian function during AI therapy using research samples and data collected from study participants. We hypothesize that we can predict which women will remain postmenopausal during AI therapy, and which are highly likely to recover ovarian function. The outlined career development program, along with the mentored research proposal for this K07 application, will augment the candidate's knowledge and research skills to enable the successful transition to an independent research career in clinical and translational breast oncology. RELEVANCE: Each year, approximately 20,000 premenopausal breast cancer patients in the U.S. receive chemotherapy and endocrine therapy. Aromatase inhibitor (AI) therapy may be preferable to tamoxifen, but may not be safe in all patients because of the potential for recovery of ovarian function. In this proposal we will identify those patients who can receive AI therapy safely, which will enable more personalized treatment decisions.