Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

Risk factors for breast cancer vary according to breast cancer subtype. This study analyzes the impact of potential risk factors in breast cancer by androgen receptor (AR) status.

A total of 17,035 women were followed in the population-based prospective Malmö Diet and Cancer Study. Baseline data included lifestyle factors including anthropometry, reproductive history, and exogenous hormone use. During follow-up (mean: 12.8 years), 747 invasive breast cancers were diagnosed. Expression of AR was determined by immunohistochemistry in tumor tissue microarrays.

AR status was assessable in 516 of 747 tumors (69%). Among these, 467 tumors (90.5%) were AR positive (AR⁺) and 49 tumors (9.5%) were AR negative (AR^-). AR negativity was significantly associated with estrogen receptor (ER) and progesterone receptor negativity, higher grade and proliferation (Ki67). Cox regression analyses stratified by AR status showed significant associations between reproductive factors and AR^- breast cancer. The older the woman at first childbirth the higher the risk of AR^- breast cancer; adjusted HR_≤20yrs = 0.35, HR_{>20–≤25yrs} = 0.62, HR_nulliparous = 1.00, HR_{>25–≤30yrs} = 1.29, HR_>30yrs = 1.92, p _trend = 0.001. No such association was seen for AR⁺ tumors. Similarly, ever oral contraceptive use increased the risk of AR^- breast cancer [Adj. HR = 2.59, 95% CI (1.26–5.34)] compared to never use, but not for AR⁺ breast cancer.

Advanced age at first child birth and use of oral contraceptives were associated with increased risk of AR⁻ breast cancer. This study may contribute to enhanced understanding of the role of the AR in breast carcinogenesis and improve risk stratification tools for personalized breast cancer prevention.