The aim of this study is to evaluate the analysis of markers related with progression, to further characterize familial breast
cancers. Here, we investigated the expression of
breast cancer susceptibility gene-1,
hypoxia-inducible factor-1α,
vascular endothelial growth factor receptor 1, and
Na+/H+ exchanger regulatory factor 1 in 187 microarrayed
breast carcinomas from 94 familial and 93 sporadic
breast cancer patients by immunohistochemical staining. Furthermore, the expression levels of these
biomarkers were compared with triple-negative phenotype. Familiarity was significantly associated with younger age (P < .000), higher
tumor grade (P = .038), negative
estrogen receptor hormonal status (P = .036), and high proliferative activity (P = .029). The familial
cancers were immunonegative for membranous
Na+/H+ exchanger regulatory factor 1 expression compared with sporadic
cancers (P = .001); notably,
vascular endothelial growth factor receptor 1 staining correlated with cytoplasmic
Na+/H+ exchanger regulatory factor 1 expression in familial
tumors (P = .009). In multivariate analysis, the "new
biomarkers," including negative
human epidermal growth factor receptor 2 status (odds ratio, 4.538; 95% confidence interval, 1.756-11.728), negative membranous
Na+/H+ exchanger regulatory factor 1 expression (odds ratio, 7.686; 95% confidence interval, 1.876-31.483) and positive nuclear
breast cancer susceptibility gene-1 (odds ratio, 0.3982; 95% confidence interval, 0.169-0.936), significantly correlated with family history of
breast cancer. We hypothesize that the evaluation of
human epidermal growth factor receptor 2,
Na+/H+ exchanger regulatory factor 1, and
breast cancer susceptibility gene-1 could be clinically useful to identify familial
breast tumors and to select patients candidate to
breast cancer susceptibility genes 1/2 gene sequencing.