Predictors of ovarian failure after chemotherapy in young breast cancer patients

年轻乳腺癌患者化疗后卵巢衰竭的预测因素

• 批准号: 8104288
• 负责人: Hui-Chun Irene Su
• 金额: $ 10.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8104288
• 关键词: 10 year old; Adjuvant; Adjuvant Chemotherapy; Age; Aging; American; Antral; Award; Biological Markers; Biological Preservation; Blood; Caliber; Cancer Patient; Cancer Prognosis; Cancer Survivor; Chemotherapy-Oncologic Procedure; Clinical; Cohort Studies; Complex; Counseling; Cyclophosphamide; Data; Diagnosis; Discipline; Disease; Enrollment; Environmental Risk Factor; Enzymes; Failure; Fertility; Follicle Stimulating Hormone; Genetic; Genetic Polymorphism; Goals; Hemorrhage; Hormonal; Human; Image; Learning; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Medical; Menopause; Mentors; Methods; Oocytes; Operative Surgical Procedures; Ovarian; Ovary; Patients; Pattern; Pelvis; Pharmaceutical Preparations; Physicians; Physiology; Premenopause; Principal Investigator; Process; Reproduction; Reproductive History; Research; Research Personnel; Survivors; Testing; Time; Ultrasonography; Woman; aged; base; cancer diagnosis; cancer therapy; chemotherapy; cohort; diaries; fetal; follow-up; genetic epidemiology; high risk; indexing; inhibin B; interest; malignant breast neoplasm; mullerian-inhibiting hormone; predictive modeling; prospective; public health relevance; reproductive; reproductive epidemiology; tool

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.

描述（由申请人提供）：该指导研究奖将为候选人成为生殖流行病学的独立研究者做好准备。具体来说，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模型的方法； 3）与多个学科的研究人员合作； 4) 收集 R01 提交的数据。 超过两百万美国女性是乳腺癌幸存者。大量患有乳腺癌的育龄妇女提供了一个独特的机会来研究这种破坏性疾病和治疗对卵巢衰老和生殖的影响。准确描述和预测年轻乳腺癌患者的卵巢功能对于幸存者来说是一个重要问题，因为这会影响生育力、更年期和癌症生存等生殖问题。目前化疗后卵巢衰竭的预测因素仅限于年龄和化疗方案。 该提案的目标是确定与辅助化疗后卵巢衰竭相关的重要激素、遗传和卵巢形态测量标记。建议对绝经前乳腺癌患者进行一项为期 5 年的前瞻性队列研究，从诊断到化疗后进行随访。我们将测试以下假设：1）。化疗前抗苗勒氏管激素和抑制素B水平较低、化疗前FSH水平较高的乳腺癌患者在辅助化疗后更容易出现卵巢功能衰竭； 2）。药物代谢酶多态性导致环磷酰胺暴露较高的乳腺癌患者在以环磷酰胺为基础的辅助化疗后更容易发生卵巢功能衰竭； 3）。化疗前卵巢体积、直径和窦卵泡数量较小的乳腺癌患者，以及化疗前后这些测量值变化较大的乳腺癌患者更容易发生卵巢功能衰竭； 4).使用来自这些目标的变量可以得出预测指数，以识别治疗后卵巢衰竭高风险的患者。 公共健康相关性：本研究将确定激素、遗传和卵巢成像标记物，以预测化疗后卵巢衰竭。这些工具将帮助年轻乳腺癌患者及其医生做出影响癌症生存和繁殖的治疗决策。