Use of oral contraceptives (OC) and breast cancer risk among young women by OC formulation and breast cancer subtype

Abstract

Background: Many studies suggest a modest increased breast cancer risk is associated with recent oral contraceptive (OC) use, but risks associated with contemporary OCs and molecular subtypes of breast cancer are less well known. Estrogen and progestin doses have declined and new progestins have been used since OCs were introduced. Furthermore, the vast majority of studies have relied on self-reported OC use, rather than pharmacy data. Methods: Two studies examining invasive breast cancer risk were conducted in western Washington state. The first was a population-based interview case-control study among women ages 20-44 from 2004-2010 (985 cases, 882 controls). Logistic regression was used to estimate associations between lifetime OC use, overall risk, and breast cancer risk by subtype (estrogen receptor positive (ER+), ER-, and triple-negative (ER-/PR-/HER2-)). The second study was a nested case-control study among Group Health Cooperative health plan enrollees. Cases were ages 20-49 at diagnosis from 1990-2009 (n=1102) and controls were randomly selected (n=21952). Associations between recent OC use (within 1 year of reference date) by OC formulation and ER status were evaluated using conditional logistic regression. Results: In the first study, recent OC use for ≥5 years increased breast cancer risk (odds ratio (OR)=1.6), as well as lifetime duration of use for ≥15 years (OR=1.5). There was no statistically significant risk heterogeneity by OC formulation. ORs were generally greater among women ages 20-39. ER- cancer ORs were greater than ER+ ORs. Triple-negative breast cancer ORs were especially elevated. In the second study, recent OC use increased breast cancer risk (OR=1.6). Risk was greater for ER+ (OR=1.7) than ER- cancer (OR=1.3). Risk varied by OC formulation, with some OCs associated with an increased risk and others not associated with risk. Conclusions: We found that recent use of contemporary OCs increases breast cancer risk among women ages 20-49 and that long durations of use increases risk among ages 20-44. Risks may be greater among younger women and for triple-negative breast cancer. Risks may also vary by OC formulation. Continued monitoring of breast cancer risk is essential as OC formulations and use patterns continue to evolve.