Finding Metabolomic Signatures in Pregnancy That Predict Breast Cancer: 60-Year Prospective Study in the Child Health and Development Studies Pregnancy Cohort
Abstract
Rationale: Now, for the first time there is a new technology that can identify an individual woman’s pathway to breast cancer. The new technology is high-resolution metabolomics (HRM). HRM measures nearly all the chemical reactions in the body that result from the combination of a person’s genetic make-up and her personal internal and external exposures. These chemical reactions can be read in blood samples and linked to subsequent risk of breast cancer. Pregnancy is known to be a particularly vulnerable time. Thus now, for the first time, it is possible to trace the unique, individual response of a woman to her pregnancy to whether or not she develops breast cancer after pregnancy. Objective: We will identify a woman’s internal chemical response to her pregnancy and whether it is linked to subsequent breast cancer occurrence. This advance will make it possible to (1) predict the risk of an individual woman based on testing her blood sample during pregnancy; (2) find the reasons why she is at risk; and (3) develop a strategy to prevent her breast cancer. Aims: (1) Find chemical pathways in the second and third trimester pregnancy blood that distinguish women who go on to develop breast cancer compared to women who do not by examining archived pregnancy serum of 620 women, including 204 cases of breast cancer that were the basis of a prior study of breast cancer in The Child Health and Development Studies pregnancy population (CHDS). (2) Compare pathways by time to diagnosis after pregnancy, tumor characteristics (stage at diagnosis, receptor status), age at pregnancy, placenta shape and size, and third trimester pregnancy estrogens. Significantly, these are existing data in our study population, so this prospective (longitudinal) study is cost-effective. Overarching Challenges Addressed: (1) Identify determinants of breast cancer initiation, risk, or susceptibility in order to (2) prevent breast cancer. Types of Patients Research Will Help and How It Will Help Them: Women of reproductive age who will have a pregnancy of 7 months or more are the primary, direct beneficiaries of the proposed research. Women of reproductive age are a critical population for breast cancer prevention due to the transient increased risk of breast cancer following pregnancy and due to increasing age at first birth, a prominent breast cancer risk factor that is rising locally and globally. Most women still have at least one child, so most women can benefit. Potential Clinical Applications, Benefits, and Risks. This advance will make it possible to (1) predict the risk of an individual woman based on testing her blood sample during pregnancy; (2) find the reasons why she is at risk; and (3) develop a strategy to prevent her breast cancer. Projected Time It May Take to Achieve A Patient-Related Outcome: Within 3 years, we will find individual pathways to risk. If pathways found are well-characterized and there is a safe opportunity for prevention (such as was found for vitamin supplementation of folate to prevent the birth defect spina bifida), then specific recommendations could follow swiftly within 5 years. If the pathways are multiple and complicated, prevention may require additional new research to understand genes involved in risk and to be sure to do no harm. Likely Impact on the Breast Cancer Research Program’s Mission of Ending Breast Cancer: Pregnancy is associated with lifetime protection against breast cancer, short-term increase in risk (10 to 20 years after pregnancy), and is riskier for women with first pregnancies after the mid-20s. However, we also know that most women with breast cancer have been pregnant, some who were first pregnant when young, and that most women do not get breast cancer within 20 years after pregnancy. We have to learn how individual risk is determined to end breast cancer. The proposed project is a first step in this effort. Interim outcomes: (1) Discover new genes
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010102
Entities
People
- Barbara A Cohn
Organizations
- Public Health Institute
- United States Army