Background:
Breast cancer is a heterogeneous disease with distinct molecular signatures of disease aetiology, evidenced by the joint expression of molecular tumour markers. Differential effects of oral contraceptive (OC) use on breast cancer risk by molecular subtypes have been reported. This is the first meta-analysis to investigate the associations between OC use and subsequent breast cancer risk stratified by combined estrogen receptor (ER) and progesterone receptor (PR) status alongside the Luminal A and B subtypes, which additionally consider the human epidermal growth factor receptor 2 (HER2) status.

Methods:
A systematic review and meta-analysis of case-control and cohort studies was conducted in PubMed and Web of Science. The odds ratios (ORs) were summarized using a random-effects model.

Results:
Eleven studies were analysed. Random-effects meta-analyses revealed significant increasing effects for ever-users of OCs on ER-PR- breast cancer compared to never-users (OR = 1.30, 95% CI: 1.07 -1.56, p 4 years compared to never-users (OR = 1.74, 95% CI: 1.15-2.63, p 4 years is associated with an increased breast cancer risk, pertaining to the estrogen and progesterone double negative breast cancer subtype. Large-scale prospective observational studies comprising more comprehensive molecular signatures of breast cancer aetiology, including HER2 status, are needed.