Predictors of ovarian failure after chemotherapy in young breast cancer patients

项目负责人/主要研究者（最后，第一，中间）：Su，H。艾琳 项目总结（见说明）： 这个指导研究奖将准备候选人成为一个独立的调查员， 生殖流行病学具体而言，该提案将使主要研究者能够：1）进行 前瞻性队列研究; 2）学习遗传流行病学和预测建模方法; 3）合作 与研究人员多学科;和4）收集数据的R 01提交。 超过200万美国女性是乳腺癌幸存者。大自然 生育年龄女性乳腺癌患者的数量提供了一个独特的机会来研究 这种毁灭性的疾病和治疗对卵巢衰老和生殖的影响。准确表征和 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， 对生育、更年期和癌症存活率等生殖问题的影响。当前预测因素 化疗后卵巢功能衰竭的发生率受年龄和化疗方案的限制。 这项建议的目标是确定显着的激素，遗传和卵巢形态学标记 与辅助化疗后卵巢功能衰竭有关。一项5年前瞻性队列研究， 绝经期乳腺癌患者，从诊断到化疗后，提出。我们将测试 假设：1）。化疗前抗苗勒管激素较低的乳腺癌患者， 卵泡刺激素B水平和化疗前较高的卵泡刺激素水平将更有可能 辅助化疗后出现卵巢功能衰竭; 2）.乳腺癌患者药物代谢 酶多态性导致更高的环磷酰胺暴露更容易发展卵巢癌， 以环磷酰胺为基础的辅助化疗后失败; 3）。乳腺癌患者的术前 化疗卵巢体积、直径和窦卵泡计数，以及这些指标的较大变化- 化疗前和化疗后的患者更容易发生卵巢功能衰竭; 4）.预测指数使用 可以从这些目标中导出变量，以识别治疗后卵巢衰竭的高风险患者。 相关性（参见说明）： 这项研究将确定激素，遗传和卵巢成像标志物，以预测卵巢衰竭后， 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 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.