Grant Number:	5R01CA279145-02 Interpret this number
Primary Investigator:	Houghton, Lauren
Organization:	Columbia University Health Sciences
Project Title:	The Spectrum Study
Fiscal Year:	2025

Females have the highest rates of breast cancer but national and global cancer registries support major increases in incidence in both male and female breast cancer. Exogenous use of estrogens and progesterone are known to increase the risk of breast cancer in females. It is unknown, however, whether and how various other exogenous and endogenous hormones, modify breast cancer risk in females and males. Current breast cancer screening guidelines are not tailored based on exogenous hormone exposure. Current evidence lacks understanding of the effect of exogenous hormone exposure on the entire steroid metabolome and what this means for breast cancer risk. We hypothesize that exogenous hormones modify the steroid metabolome and subsequent breast cancer risk in males and females. We will test our hypothesis by recruiting individuals (aged 25-50 years) with varying exogenous and endogenous hormone exposures. We will conduct the following aims: Aim 1) Quantify exogenous hormone exposure (n=5000) and examine the association between exogenous exposure and the steroid metabolome in a subset of the group (n=1200), Aim 2) Evaluate longitudinal changes in the steroid metabolome based on age, hormone exposure, and organ inventory (n=600), Aim 3) Incorporate hormonal evidence into screening guidelines using the Delphi method with 10 experts. Our approach uses a novel, validated comprehensive assay panel to measure 27 steroid metabolites of estrogens, progesterone, androgens, and glucocorticoids in dried urine with reproducible results. Few large-platform metabolomic assays measure steroid metabolites; other steroid assays only measure single hormones. We will measure the steroid metabolome in males and females, using a robust study design to obtain a study sample with a mixture of endogenous and exogenous hormones. Our study provides a valuable resource to understand the hormonal etiology of breast cancer at the molecular level. Such knowledge is lacking yet could greatly improve screening recommendations, which do not account for endogenous and exogenous drivers of the full steroid metabolome. These results will directly inform breast screening guidelines to help prevent current delays in detection.





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