Predictors of ovarian failure after chemotherapy in young breast cancer patients

描述（由申请人提供）：这个指导研究奖将准备候选人成为生殖流行病学的独立调查员。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）学习遗传学流行病学和预测建模方法; 3）与多个学科的研究人员合作; 4）收集R 01提交的数据。 超过200万美国女性是乳腺癌幸存者。大量的育龄妇女乳腺癌提供了一个独特的机会，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，因为这会影响生育、绝经和癌症生存等生殖问题。目前化疗后卵巢功能衰竭的预测因素仅限于年龄和化疗方案。 本研究的目的是确定与辅助化疗后卵巢功能衰竭相关的重要激素、遗传和卵巢形态学标志物。一项为期5年的前瞻性队列研究，绝经前乳腺癌患者，从诊断到化疗后，建议。我们将检验以下假设：1）。化疗前抗苗勒管激素和FSH B水平较低、化疗前FSH水平较高的乳腺癌患者，辅助化疗后发生卵巢功能衰竭的可能性较大; 2）.具有药物代谢酶多态性导致环磷酰胺暴露量较高的乳腺癌患者更容易在基于环磷酰胺的辅助化疗后发生卵巢功能衰竭; 3）。乳腺癌患者化疗前卵巢体积、直径和窦卵泡计数较小，化疗前后这些测量值变化较大，更容易发生卵巢功能衰竭; 4）。使用这些目标的变量的预测指数可以用来识别治疗后卵巢功能衰竭的高风险患者。 公共卫生相关性：这项研究将确定激素，遗传和卵巢成像标志物，以预测化疗后卵巢衰竭。这些工具将帮助年轻的乳腺癌患者及其医生做出影响癌症生存和繁殖的治疗决定。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.