Abstract
BackgroundPolymorphisms in the excision repair cross-complimentary group 1 (ERCC1) gene have been involved in the prognosis of various cancers. In the present study, we evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy.MethodsA total of 47 patients with T4 breast cancer undergoing treatment with a platinum-based regimen were collected and followed up (median 159 months; range, 42–239 months). ERCC1 C8092A (rs3212986) and T19007C (rs11615) polymorphisms were genotyped, using an automated sequencing approach. The same series was screened for BRCA1/2 mutations by DHPLC analysis and DNA sequencing.ResultsAmong the tested patients, 16 (34%) and 25 (53%) presented the 8092A (homo-zygosity A/A or heterozygosity A/C) and the 19007C (homozygosity C/C or heterozygosity C/T) genotypes, respectively. The 8092A and 19007C genotypes in ERCC1 were significantly associated with overall survival in T4 breast cancer patients treated with chemotherapy containing platinum (p-values = 0.036 and 0.004, respectively). Univariate and multivariate Cox regression analyses showed that combination of 8092A and 19007C genotypes acts as a significant prognostic factor in women with T4 breast cancer receiving platinum-based chemotherapy (p-values = 0.022 and 0.049, respectively). Two (4.3%) out of 47 cases were found to carry BRCA1/2 mutations; they presented the highest overall survival rates into the series.ConclusionsThe ERCC1 8092A and 19007C genotypes or their combination may predict a favorable prognosis in T4 breast cancer patients undergoing a platinum-based treatment. Further large-scale, prospective studies are needed to validate our findings.
Highlights
Breast cancer remains the most frequent tumor and the leading cause of cancer-related death among the female population worldwide [1].Locally advanced breast cancer (LABC) represents a heterogeneous group of diseases associated with a poor prognosis
The aim of the present study was to investigate whether the excision repair cross-complimentary group 1 (ERCC1) 19007C > T and 8092C > A polymorphisms may influence the clinical outcome in response to treatment with platinum within a well-characterized cohort of patients with T4 breast carcinoma and long follow-up evaluation
Since germline mutations in BRCA1 and, to a less extent, BRCA2 genes have been found in a variable proportion of patients with LABC or, mostly, triple-negative breast cancer [28], and such gene dysfunctions seem to be associated with prognosis [29], we evaluated the prevalence of BRCA1-2 mutations in our series
Summary
Breast cancer remains the most frequent tumor and the leading cause of cancer-related death among the female population worldwide [1].Locally advanced breast cancer (LABC) represents a heterogeneous group of diseases associated with a poor prognosis. Patients with LABC - including cases presenting an inflammatory disease and, mostly, those carrying a triple-negative breast cancer - are responsive to DNA-damaging agents such as platinum compounds; for this reason, platinum-based chemotherapy is frequently used as neoadjuvant treatment in such disease types [3,4,5,6]. The cytotoxic effect of platinum drugs is ascribed to the formation of bulky platinum-DNA adducts, which block replication and transcription through inter-strand cross-link of the two DNA strands, leading to cancer cell death. These adducts are recognized and removed, with subsequent repair of the inter-strand cross-links in DNA, by factors of the nucleotide excision repair (NER) pathway [7]. We evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy
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