Prevalence of mutations in BRCA and homologous recombination repair genes and real-world standard of care of Asian patients with HER2-negative metastatic breast cancer starting first-line systemic cytotoxic chemotherapy: subgroup analysis of the global BREAKOUT study

Germline mutations; Homologous recombination repair; Somatic mutationsMutaciones de la línea germinal; Reparación de recombinación homóloga; Mutaciones somáticasMutacions de la línia germinal; Reparació de recombinació homòloga; Mutacions somàtiquesBackground The multinational BREAKOUT study (NCT03078036) sought to determine the prevalence of germline BRCA1/2 (gBRCA1/2) and somatic BRCA1/2 (sBRCA1/2) mutations and mutations in other homologous recombination repair (HRR) genes in women with HER2-negative metastatic breast cancer (MBC) starting first-line chemotherapy. Methods Genetic testing for gBRCA, sBRCA, and HRR gene mutations was performed in patients who started first-line chemotherapy for MBC in the last 90 days (341 patients across 14 countries) who were not selected based on risk factors for gBRCA mutations. We report data from the Asian cohort, which included patients in Japan (7 sites), South Korea (10 sites), and Taiwan (8 sites). Results Of 116 patients screened, 104 patients were enrolled in the Asian cohort. The median age was 53.0 (range 25–87) years. gBRCA1/2, gBRCA1, and gBRCA2 mutations were detected in 10.6% (11/104), 5.8% (6/104), and 4.8% (5/104) of patients, respectively; none had mutations in both gBRCA1 and gBRCA2. gBRCA1/2 mutations were detected in 10.0% (6/60) and 11.6% (5/43) of patients with hormone receptor-positive and triple-negative MBC, respectively. HRR gene mutations were tested in 48 patients without gBRCA mutations, and 5 (10.4%) had at least one HRR mutation in sBRCA, ATM, PALB2, and CHEK2. Conclusion We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC.This study was funded by AstraZeneca, and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Analysis of miRNA Expression in Breast Cancer

Triple-negative breast cancer (TNBC), lacking estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor (HER2) expression, is resistant to conventional therapies. Recent studies have focused on microRNAs (miRNAs) as novel molecular targets for treating TNBC because they modulate gene expression and tumor progression. In the current study, we analyzed the expression of selected miRNAs (miR-145 and miR-182) and tumor promoting factors such as Fascin and poly (ADP-ribose) polymerase (PARP) in human TNBC tissues and "Luminal A" breast cancer tissues, which express ER and PgR, but not HER2, as well as breast cancer cell lines including the triple-negative MDA-MB-231 and Luminal A MCF-7. The results showed that miR-145 and miR-182 were expressed in Luminal A breast cancer tissues and MCF-7 cells, but not in TNBC tissues and MDA-MB-231 cells. In contrast, Fascin and PARP proteins were highly expressed in TNBC and MDA-MB-231, but poorly expressed in Luminal A tissues and MCF-7 cells, indicating a negative correlation between expression of these miRNAs and that of the tumor promoting factors Fascin and PARP. The current study therefore suggests that miR-145 and miR-182 could be potential novel therapeutic targets for TNBC therapy