Abstract P3-07-35: Findings from the first prospective womb to breast cancer study: New gestational biomarkers support proof of concept that gestation is a window of susceptibility for the breast
Authors: Cohn Barbara , Krigbaum Nickilou , Zimmermann Lauren , Cirillo Piera 
Published: May 2015

Abstract
Rationale. Here we provide the first prospective evidence for proof of concept that gestation is an important window of susceptibility for breast cancer. These findings could open the field to interdisciplinary investigation of mechanisms, and interventions via clinical and experimental science.
Objective. We tested the hypothesis that biomarkers in gestation predict early-onset breast cancer. Data were prospectively collected including maternal and paternal peri-conceptual body mass, tobacco and alcohol use, maternal pregnancy weight gain, pregnancy complications and outcomes, placental morphology assessed by a standardized examination at birth, and environmental chemicals recently assayed in archived maternal perinatal serum samples. This investigation was based on the observation of 20,000 pregnancies beginning in 1959, with surveillance for both maternal (F0) and offspring (F1) cancer in the Child Health and Development Studies pregnancy cohort. This report is based on the first 133 breast cancer cases in F1 that occurred from 1992-2012, diagnosed at ages 32 to 52.
Results. We observed gestational biomarkers of breast cancer risk which were independent of maternal history of breast cancer and race. Highlights of significant findings include independent, higher risk for women who: were born to mothers who lost weight during pregnancy (3-fold increase in risk, p&lt;0.03), were growth retarded in utero (3-fold increased risk, p&lt;0.01), were born with thick (p&lt;0.01), but small diameter placentas (p&lt;0.04), whose mothers had higher perinatal serum levels of environmental chemicals including o,p'-DDT (2.5-fold increase in risk for upper quartile, p&lt;0.03), perfluorooctanesulfonic acid (PFOS) precursors (p&lt;0.03) and total cholesterol (p&lt;0.04). Maternal floor infarction of the placenta was a protective factor both for mothers and their daughters. In ancillary studies we observed that F1 breast density at mid-life is also impacted by placental morphology during F1 gestation.
Conclusions. Here we provide a high level of evidence for the existence of gestational biomarkers for breast cancer. Prospective design and direct clinical observation of pregnancies eliminates reporting and misclassification bias. Findings extend the discussion of gestational biomarkers beyond birthweight and pre-eclampsia which have been previously reported. The importance of the gestation window for breast cancer in humans is in line with toxicological evidence in animal models and strongly suggests the existence of opportunities for primary prevention beginning before birth.
Citation Format: Barbara Cohn, Nickilou Krigbaum, Lauren Zimmermann, Piera Cirillo. Findings from the first prospective womb to breast cancer study: New gestational biomarkers support proof of concept that gestation is a window of susceptibility for the breast [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-35.