Abstract 1206: HER2/neu positive receptor status is associated with a low DNA repair capacity in women with breast cancer

Abstract

Abstract Hormone receptor status are now routinely used for therapy selection in breast cancer (BC). Estrogen receptor status is routinely use for the selection of tamoxifen adjuvant therapy after surgery. Substantial evidence now indicates that patients with BC tumors that have overexpression of the HER2/neu receptor have generally a poor prognosis. Approximately 15-20 percent of BC patients have an amplification of the HER2/neu gene. Overexpression of HER2/neu is associated with increased BC recurrence and worse prognosis. Because of its prognostic role as well as its ability to predict response to trastuzumab (Herceptin), breast tumors are routinely checked for overexpression of HER2/neu. Strategies targeting DNA repair defects for the treatment of patients with triple-negative and BRCA mutation-associated BC have received much attention recently, however the relationship between HER2/neu receptor status and the phenotypic expression of DNA repair capacity (DRC) measured in lymphocytes has never been previously examined. DRC is an important risk factor for several types of cancer including BC. In this study, we examined the association between BC and DRC and the status of estrogen, progesterone and HER2/neu receptors. Our main objective was to determine if levels of DRC measured in lymphocytes using a host cell reactivation assay with a luciferase reporter gene are associated with receptor status. The estrogen, progesterone and HER2/neu receptor status, DRC levels, and other selected covariates were compared among 125 Hispanic women with histopathologically confirmed BC. After variable transformation, the mean DRC was compared between positive and negative HER2/neu BC patients using the t-test and the Wilcoxon's test to assess the statistical significance of the mean DRC difference. Crude and multiple logistic regression adjusted odds ratios (OR) were used as measures of association when compared HER2/neu (+) with (−) BC patients. The two-sided Wald test was used to assess the adjusted OR statistical significance. BC women with a HER2/neu (+) (n=14) had 4.1 times more odds of having a low DRC (< 1.78) compared with those that were HER2/neu (−) (n=65): (OR = 4.3 (95% CI 1.1, 16.6) p = 0.047. The average DRC in controls without BC was 6.10% (n=560). Women with BC that were HER2/neu (+) had an average DRC of 1.6% while BC patients that were HER2/neu (−) had 2.4%, this difference was significant (p=0.008). No significant differences were evident in regards to the association between DRC and the status of estrogen and progesterone receptors (double negatives) nor with triple negative receptor status (estrogen, progesterone and HER2/neu).These results indicate that low DRC could, at least partially explain, why HER2/neu (+) tumors are more aggressive. Supported by the NCI Diversity Training Branch of the Center to Reduce Cancer Health Disparities through the MBRS SCORE Program (Grant SO6 GM008239-23). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1206. doi:10.1158/1538-7445.AM2011-1206