This mentored research award will prepare the candidate to become an independent investigator in reproductive epidemiology. Specifically, this proposal will enable the principal investigator to: 1) conduct a prospective cohort study;2) learn methods in genetics epidemiology and predictive modeling;3) collaborate with researchers in multiple disciplines;and 4) gather data for an R01 submission. More than two million American women are breast cancer survivors. The large number of reproductive aged women with breast cancer provides a unique opportunity to study the impact of this devastating disease and treatment on ovarian aging and reproduction. Accurately characterizing and predicting ovarian function in young breast cancer patients is an important issue to survivors because of implications on reproductive issues such as fertility and menopause and cancer survival. Current predictors of ovarian failure after chemotherapy are limited to age and chemotherapy regimen. The goal of this proposal is to identify significant hormonal, genetic and ovarian morphometric markers associated with ovarian failure after adjuvant chemotherapy. A 5-year prospective cohort study of pre-menopausal breast cancer patients, followed from diagnosis to post-chemotherapy, is proposed. We will test the hypotheses that: 1). Breast cancer patients with lower pre-chemotherapy anti-Mullerian hormone and inhibin B levels and higher pre-chemotherapy FSH levels will be more likely to develop ovarian failure after adjuvant chemotherapy;2). Breast cancer patients with drug metabolizing enzyme polymorphisms resulting in higher cyclophosphamide exposure are more likely to develop ovarian failure after cyclophosphamide-based adjuvant chemotherapy;3). Breast cancer patients with smaller pre-chemotherapy ovarian volume, diameter and antral follicle count, and larger changes in these measurements pre- and post-chemotherapy are more likely to develop ovarian failure;4). A predictive index using variables from these aims can be derived to identify patients at high risk for ovarian failure after therapy.
This study will identify hormonal, genetic and ovarian imaging markers to predict ovarian failure after chemotherapy. These tools will assist young breast cancer patients and their physicians in making treatment decisions that would impact cancer survival and reproduction.
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