Abstract A126: Oral contraceptives and late first childbirth increase the risk of androgen receptor-negative breast cancer: The Malmö Diet and Cancer cohort
Authors: Elebro Karin , Butt Salma , Dorkhan Mozhgan , Jernström Helena , Borgquist Signe 
Published: May 2015

Aim: The importance of the androgen receptor (AR) as a prognostic factor and a possible treatment target is currently debated. However, the impact of lifestyle factors on AR status in breast cancer has not yet been addressed. The aim of this study was to evaluate the influence of hormonal lifestyle factors on AR-defined breast cancer risk.

Materials and methods: The population-based prospective Malmö Diet and Cancer Study including 16,459 women were followed using record-linkage with national cancer registries. Baseline data of all women in the cohort included socioeconomic factors, reproductive factors including use of exogenous hormones and anthropometry. During an average follow-up of 12.8 years, 747 cases of invasive breast cancer were diagnosed. AR was assessed immunohistochemically by monoclonal antibody Ab-1 (Clone AR441, Thermo Scientific, USA). A tumor was considered AR positive (AR+) when &gt;10% positive nuclei. A valid AR score was obtained from 516 tumors. The expression of ER, PR, Ki67 along with information on HER2 status, tumor size, histological type, tumor grade and axillary lymph node involvement was obtained. Reproductive factors were compared with tumor characteristics based on AR status. Distribution of clinicopathological data and odds ratios in relation to AR status were analyzed. Hazard ratios (HR) were calculated using Cox's proportional hazards analysis. Survival analyses in relation to AR status were carried out using Kaplan-Meier Log Rank test.

Results: A total of 467 tumors (90.5%) were AR+ and 49 tumors (9.5%) were AR negative (AR-). AR positivity correlated significantly to lower tumor grade, lower proliferation and ER and PR co-expression. There was a significant trend of increasing risk of AR- breast cancer by increasing age at first childbirth (HR&lt;20 yrs=0.37, HR21-25 yrs =0.76, HRnulliparous=1.00, HR26-≥30 yrs=1.35, HR&gt;30 yrs =2.01, Ptrend=0.002 among parous women). The risk for AR+ breast cancer was not affected by age at first birth. Ever oral contraceptive (OC) users had an increased risk of AR- breast cancer (HR=2.10, 95% CI 1.16-3.81, P=0.015) compared to never users. OC use was neither associated with risk for breast cancer in general nor with AR+ breast cancer. The use of combined estrogen and progestin hormonal replacement therapy (cHRT) was significantly associated with increased risk for breast cancer (HRall=2.13, P=&lt;0.0001) irrespective of AR status (HRAR-=2.35, P=0.014, HRAR+=2.03, P=&lt;0.0001) compared to non-users of HRT and irrespective of prior OC use. None of the anthropometric measures differed according to AR status.

Conclusion: In conclusion, reproductive factors and exogenous hormones influenced the risk for AR-defined breast cancer. Specifically, the older the age at first childbirth, the higher the risk for AR- breast cancer. Similarly, ever OC users had a higher risk of AR- breast cancer compared to never users. This study contributes to a deepened understanding of AR in relation to breast cancer risk factors and may yield improved risk stratification tools for breast cancer prevention and treatment.

Citation Format: Karin Elebro, Salma Butt, Mozhgan Dorkhan, Helena Jernström, Signe Borgquist. Oral contraceptives and late first childbirth increase the risk of androgen receptor-negative breast cancer: The Malmö Diet and Cancer cohort. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A126.