Abstract
Breast cancer (BC) is a heterogeneous disease which many studies have classified in at least four molecular subtypes: Luminal A, Luminal B, HER2-Enriched, and Basal-like (including triple-negative breast cancer, TNBC). These subtypes provide information to stratify patients for better prognostic predictions and treatment selection. Individuals vary in their sensitivities to carcinogens due to differences in their DNA repair capacity (DRC) levels. Although our previous case-control study established low DRC (in terms of NER pathway) as a BC risk factor, we aim to study this effect among the molecular subtypes. Therefore, the objectives of this study include investigating whether DRC varies among molecular subtypes and testing any association regarding DRC. This study comprised 267 recently diagnosed women with BC (cases) and 682 without BC (controls). Our results show a substantial variability in DRC among the molecular subtypes, with TNBC cases (n = 47) having the lowest DRC (p-value < 0.05). Almost 80 percent of BC cases had a DRC below the median (4.3%). Low DRC was strongly associated with the TNBC subtype (OR 7.2; 95% CI 3.3, 15.7). In conclusion, our study provides the first report on the variability among the molecular subtypes and provides a hypothesis based on DRC levels for the poor prognosis of TNBC.
Highlights
IntroductionBreast cancer (BC) is the most common cancer affecting women [1]
Worldwide, breast cancer (BC) is the most common cancer affecting women [1]
Afterwards, a bivariate analysis was performed for assessing the association between different BC risk factors and molecular subtype of BC, in order to identify the potential confounders for this association
Summary
Breast cancer (BC) is the most common cancer affecting women [1]. In the U.S and Puerto Rico, BC accounts for 30% of all new cancers in women [2,3]. While high-throughput gene expression analysis continues to reveal more distinctions between BC subtypes, their classification is still in flux. What collectively has been known as triple-negative breast cancer (TNBC) is yielding distinct genetic profiles for basal-like and claudin-low BC (the latter seeming to be an intermediate between basal-like and luminal BC) [8,9]. Immunohistochemistry (IHC) for receptor status and gene expression is a frequently used surrogate tool to classify BC subtypes. Under IHC auspices, Luminal A is ER+, PR+/−, HER2−; Luminal B is positive for ER and PR+/− but is
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