, Volume 19, Issue 5, pp 1499-1507
Date: 17 Dec 2011

Loss of Heterozygosity at BRCA1 Locus Is Significantly Associated with Aggressiveness and Poor Prognosis in Breast Cancer

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Abstract

Background

BRCA1 and BRCA2 are two major tumor suppressor genes for hereditary breast and ovarian cancer. In sporadic breast cancer, although somatic mutations of these genes are rare, loss of heterozygosity (LOH) at BRCA1 and BRCA2 loci is common.

Methods

LOH at BRCA1 and BRCA2 loci were investigated in 202 Japanese invasive breast cancer patients. The relationships between LOH at these gene loci and clinicopathologic characteristics were analyzed.

Results

Among 166 informative cases for both BRCA1 and BRCA2 loci, 69 (41.6%) and 52 (31.3%) tumors revealed LOH at BRCA1 and BRCA2 loci, respectively. LOH at BRCA1 LOH or BRCA2 locus was associated with higher nuclear grade (P < 0.0001, P = 0.0187). LOH at BRCA1 locus was associated with estrogen receptor and progesterone receptor negativity (P = 0.001 and P = 0.015) and significantly shorter disease-free survival (P < 0.0001), distant metastasis-free survival (P < 0.0001), and overall survival (P < 0.0001). In contrast, LOH at BRCA2 locus had no associations with estrogen receptor or progesterone receptor status and prognosis. LOH at BRCA1 locus was independently associated with poor prognosis in terms of disease-free survival (hazard ratio 3.08, 95% confidence interval [CI] 1.58–6.18, P = 0.0009), distant metastasis-free survival (hazard ratio 5.18, 95% CI 2.35–12.19, P < 0.0001), and overall survival (hazard ratio 4.97, 95% CI 1.84–15.1, P = 0.0013).

Conclusions

LOH at BRCA1 locus could be an independent prognostic biomarker useful in identifying a subgroup of patients with poor prognosis.