Predictors of ovarian failure after chemotherapy in young breast cancer patients

项目主任/首席调查员(最后、第一、中间)：苏、H·艾琳 项目总结(见说明)： 这项指导研究奖将为候选人成为一名独立的调查员做好准备 生殖流行病学。具体地说，这项建议将使首席调查员能够：1)进行 前瞻性队列研究；2)学习遗传学、流行病学和预测性建模的方法；3)合作 与研究人员进行多学科合作；4)为R01提交收集数据。 200多万美国女性是乳腺癌幸存者。大核桃 MBER为研究育龄妇女乳腺癌的影响提供了独特的机会 这种毁灭性的疾病和治疗对卵巢的衰老和生殖都有影响。准确地描述和 预测年轻乳腺癌患者的卵巢功能对幸存者来说是一个重要的问题，因为 对生育、更年期和癌症存活率等生殖问题的影响。当前预报器 化疗后卵巢衰竭的发生率仅限于年龄和化疗方案。 这项建议的目标是确定重要的激素、遗传和卵巢形态测量标记。 与辅助化疗后卵巢衰竭相关。一项为期5年的前瞻性队列研究 建议对绝经期乳腺癌患者进行从诊断到化疗后的随访。我们将测试 假设：1)。乳腺癌患者化疗前抗苗勒氏激素和 抑制素B水平和化疗前较高的卵泡刺激素水平将更有可能 2)辅助化疗后发生卵巢衰竭；乳腺癌患者的药物代谢 导致环磷酰胺暴露较高的酶基因多态性更有可能发展为卵巢 以环磷酰胺为主的辅助化疗失败；乳腺癌患者较小的前驱 化疗后卵巢体积、直径和有腔卵泡数，以及这些指标的较大变化- 化疗前后卵巢功能衰竭的发生率较高；使用以下功能的预测指数 这些目标的变量可以用来确定治疗后卵巢衰竭的高危患者。 相关性(请参阅说明)： 这项研究将确定激素、遗传和卵巢成像标志物来预测卵巢功能衰竭 化疗。这些工具将帮助年轻的乳腺癌患者和他们的医生进行治疗 会影响癌症生存和繁殖的决定。

Program Director/PrincipalInvestigator (Last, First, Middle): Su, H. Irene PROJECT SUMMARY (Seeinstructions): 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 multiple disciplines; and 4) gather data for an R01 submission. More than two million American women are breast cancer survivors. The large nu mber 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 Follicle Stimulating Hormone 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 measure- ments 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. RELEVANCE (Seeinstructions): 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.