Pregnancy-Related Factors and Breast Cancer Risk for Women Across a Range of Familial Risk

Area of Science:

• Reproductive health and cancer epidemiology.
• Genetics and personalized medicine in oncology.

Background:

• Few studies explore how pregnancy-related factors affect breast cancer (BC) risk based on individual susceptibility.
• Understanding these variations is key for BC etiology and risk-stratified screening guidelines.

Purpose of the Study:

• To investigate the association between pregnancy-related factors and BC risk.
• To examine if these associations are modified by polygenic risk scores (PARS) for BC.

Main Methods:

• A cohort study of 17,274 women from the prospective Family Study Cohort (ProF-SC) was conducted.
• Data from 1992-2011 were analyzed through 2017, using Cox proportional hazards regression to assess BC risk associated with parity, age at first full-term pregnancy (FTP), breastfeeding, and time since last FTP.
• Associations were examined for modification by PARS and stratified by estrogen receptor (ER) status.

Main Results:

• Higher PARS interacted with recent pregnancy (0-5 years post-FTP) to increase overall BC risk (HR for interaction: 1.53).
• For ER-negative BC, higher PARS amplified risk associated with recent pregnancy (HR for interaction: 1.54) and increasing years since last FTP.
• ER-negative BC risk was also associated with earlier age at first FTP (≥20 years) and inversely with multiparity, particularly among women with higher PARS.

Conclusions:

• Pregnancy-related factors and BC risk associations are modified by PARS, particularly for ER-negative BC.
• These findings highlight the interplay between reproductive history, genetic susceptibility, and BC development, informing personalized risk assessment.