Daniel Herrero

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.

Background: Male breast cancer (MBC) accounts for less than 1% of breast cancer, requiring extrapolation of results from studies in women. The aim of the study is to evaluate prognostic and therapeutic factors with special focus in endocrine treatment (ET) on the disease outcome.Methods: Observational, retrospective, single-center study of 53 MBC treated between January 1997 and December 2018 participated in the study. Among the participants, 48 patients had a performance status (PS) 0-1 (91%), 48 were hormone-receptor-positive (91%) and 4 were human epidermal growth factor 2 receptor (HER2) positive (8%). A total of 45 patients (85%) were treated with ET, with 36 patients (68%) receiving treatment in an adjuvant setting. The association analysis was performed using Chi-square test and survival was estimated using Kaplan-Meier with SPSS v25. Results: The cohort had a median age of 68 years old (range: 40-88). We found that 84% had a non-metastatic breast cancer. A breast cancer gene (BRCA) analysis was carried out in 43% of the patients, showing BRCA2 mutated in 26.1% of those analyzed, without obtaining a benefit in overall survival (P=0.698). The analysis showed higher 5-year overall survival (OS) for PS 0 (P=0.010), absence of vascular invasion (P=0.033), Ki67 ?14% (P=0.041) and absence of metastasis at diagnosis (p<0.0001). Patients receiving adjuvant ET above 5 years had a longer median OS (89 vs 69.6 months, P=0.024), disease-free survival (DFS), and distant relapse (84 vs 48 months; P=0.005, and P=0.002, respectively).Conclusions: Several prognostic factors for male breast cancer have been described. Noteworthy, patients receiving adjuvant ET above 5 years had a higher OS and DFS. BRCA did not show prognostic value in OS in this cohort. Further studies with larger sample size are necessary.