Abstract P1-05-17: Interrogating the impact of pregnancy on breast cancer biology using DNA copy number profiling

Abstract

Abstract Background Epidemiological evidence indicates a clear relationship between pregnancy and breast cancer (BC) risk. However, little is known regarding the impact of pregnancy on BC biology. DNA copy number aberrations (CNAs) play an important role in breast carcinogenesis. BC during pregnancy is a rare disease but yet could serve as a good model to study the impact of pregnancy on BC biology. Methods We retrospectively included 54 pregnant and 113 non-pregnant BC patients matched for age and stage with complete clinico-pathological, gene expression and 5-year follow-up data. CNAs were assessed using Affymetrix OncoScan FFPE arrays. We identified the CNAs associated with pregnancy using a multivariate logistic regression adjusted for classical clinico-pathological features. We further evaluated their impact on gene expression. Results After quality control, CNA profiles were obtained for 38 pregnant and 87 non-pregnant BC patients. We identified 13 regions with copy number gains, 11 of which were more frequently gained in pregnant compared to non-pregnant controls and 5 regions with copy number loss, 3 of which were more frequently lost in pregnant patients (p≤0.05). Of interest, we identified 4 genes previously identified as driver event associated with CNAs in breast cancer (S. Nik-Zainal et al, Nature 2016). AKT1 and CDKN2A/B were more frequently gained in the pregnant compared to the non-pregnant (23.7% vs. 8.0%, p=0.068 and 18.4% vs. 4.6% p=0.036) and ARID1B was less frequently gained in the pregnant cohort (2.6% vs. 13.8%, p=0.02). Interestingly, PAPPA which had been previously identified as a pregnancy-dependent oncogene (Takabatake Y. et al, EMBO Mol Med. 2016) was also more frequently gained in the pregnant compared to the non-pregnant patients (21.1% vs 5.8%, p=0.03). We next evaluated the effect of these CNAs on their own gene expression levels and found that AKT1 and CDKN2A/B CNAs were affected by gene-dosage effect. Conclusions In this study, we were able to identify several genomic alterations associated with pregnancy that could further elucidate the impact of pregnancy on BC risk. Moreover, by combining CNAs with gene expression, we were able to identify genes whose expression were associated with CNAs and therefore could be considered potential drivers of this rare disease. Citation Format: Nguyen B, Brown DN, Rothé F, Desmedt C, Majjaj S, Pruneri G, Peccatori F, Azim Jr HA, Sotiriou C. Interrogating the impact of pregnancy on breast cancer biology using DNA copy number profiling [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-17.