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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD058799-04
Application #
8104288
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Lamar, Charisee A
Project Start
2009-09-30
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$104,976
Indirect Cost
Name
University of California San Diego
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Homer, Michael V; Charo, Lindsey M; Natarajan, Loki et al. (2017) Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors. Menopause 24:663-668
Kim, Jayeon; Mersereau, Jennifer E; Su, H Irene et al. (2016) Young female cancer survivors' use of fertility care after completing cancer treatment. Support Care Cancer 24:3191-9
Seav, Susan M; Dominick, Sally A; Stepanyuk, Boris et al. (2015) Management of sexual dysfunction in breast cancer survivors: a systematic review. Womens Midlife Health 1:9
Dominick, Sally A; McLean, Mamie R; Whitcomb, Brian W et al. (2015) Contraceptive Practices Among Female Cancer Survivors of Reproductive Age. Obstet Gynecol 126:498-507
Gorman, Jessica R; Su, H Irene; Roberts, Samantha C et al. (2015) Experiencing reproductive concerns as a female cancer survivor is associated with depression. Cancer 121:935-42
Chuan, Sandy; Homer, Michael; Pandian, Raj et al. (2014) Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization. Fertil Steril 101:392-8
Gorman, Jessica R; Su, H Irene; Pierce, John P et al. (2014) A multidimensional scale to measure the reproductive concerns of young adult female cancer survivors. J Cancer Surviv 8:218-28
Dominick, Sally A; Whitcomb, Brian W; Gorman, Jessica R et al. (2014) Factors associated with pregnancy attempts among female young adult cancer survivors. J Cancer Surviv 8:571-9
Su, Hui-Chun Irene; Haunschild, Carolyn; Chung, Karine et al. (2014) Prechemotherapy antimullerian hormone, age, and body size predict timing of return of ovarian function in young breast cancer patients. Cancer 120:3691-8
Su, H Irene; Sammel, Mary D; Homer, Michael V et al. (2014) Comparability of antim├╝llerian hormone levels among commercially available immunoassays. Fertil Steril 101:1766-72.e1

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