Both BRCA1 and
Beclin 1 (BECN1) are tumor suppressor genes, which are in close proximity on the human chromosome 17q21
breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human
breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in
breast cancer, we studied their
mRNA expression patterns in
breast cancer patients from two large datasets: The
Cancer Genome Atlas (TCGA) (n=1067) and the Molecular Taxonomy of
Breast Cancer International Consortium (METABRIC) (n=1992). In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly
triple-negative) breast cancers compared to
luminal A/B intrinsic
tumor subtypes, and was also strongly associated with TP53 mutations and advanced
tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or
tumor grade. In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival. These findings suggest that decreased
mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast
cancers.