Abstract 5228: Estrogen receptor expression is associated with DNA repair capacity in breast cancer

Abstract

Abstract Estrogen receptor (ER) status is an established therapeutic and prognostic biomarker for breast cancer (BC). ER signaling has a propensity to increase proliferation, which can lead to mutations when DNA repair is dysregulated. Deficiencies in DNA repair capacity (DRC) is a hallmark of BC. Recent studies have documented interactions between ER and DNA damage response/repair. Moreover, our previous work showed that DRC in BC patients is approximately 50% less than in women without the disease (p<0.001), and a deficiency in the Nucleotide excision repair (NER) pathway figures prominently in the pathobiology of sporadic BC. Estrogen-receptor-positive (ER+) tumors employ complex signaling that engages in crosstalk with multiple pathways through genomic and non-genomic regulation. A greater understanding of these pathways is important for developing improved biomarkers that can better determine treatment choices, risk of recurrence, and cancer progression. In this study, we aimed to determine whether ER signaling influences DRC. DRC, in terms of the NER pathway, was measured in lymphocytes by means of a host cell reactivation assay with a luciferase reporter gene. A multivariate linear regression model (MLRM) was used to estimate the mean of the DRC and analyze the association between ER positivity (% receptor activation) obtained from pathological reports and DRC in 270 BC patients. These were further stratified by HER2 receptor status. An ordinal logistic regression model (OLRM) was used to confirm the relationship between DRC and ER status using the maximum likelihood method for parameters estimation. Our results show an association between ER status and mean DRC values in BC patients who have HER2-negative (HER-) tumors: that is, the mean DRC value in ER-/HER2- tumors was significantly lower as compared with ER-/HER2+ tumors (p<0.05). In contrast, the mean DRC among patients with ER+/HER2+ tumors did not significantly differ from ER-/HER2+ tumors (p>0.05). The data followed similar patterns when DRC was categorized in tertiles. In conclusion, there is an association between DRC levels and ER status, and this association is modified by HER2 receptor status. Supported by grants from the NCI Center to Reduce Health Disparities and NIH-NIGMS MBRS SCORE and RISE Programs grants # S06 GM008239-20, 9SC1CA182846-04 GM082406 and PSM-MCC Partnership grant # 5U54CA163071-04. Citation Format: Jaime L. Matta, Luisa Morales, Carmen Ortiz, Damian Adams, Wanda Vargas, Patricia Casbas, Julie Dutil, Miguel Echenique, Erick Suarez. Estrogen receptor expression is associated with DNA repair capacity in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5228.