Survival Outcomes and Efficacy of Platinum in Early Breast Cancer Patients with Germline BRCA1 or BRCA2 Mutation: A Multicenter Retrospective Cohort Study

Abstract

The study aimed to compare the survival outcomes and efficacy of platinum in early breast cancer patients with BRCA1 and BRCA2 mutations. Methods: Patients diagnosed with stage I-III breast cancer and carrying germline pathogenic/likely pathogenic BRCA mutations in three medical institutions in China from April 2016 to January 2021 were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, pathogenic variants of BRCA, and survival outcomes were collected for all eligible patients. Outcomes: One hundred and sixty-nine patients with BRCA mutations were enrolled, including BRCA1 mutation (53.3%, n = 90) and BRCA2 mutation (46.7%, n = 79). The median age was 39 years, and most patients (68.1%, n = 115) were stage I-II. Patients with BRCA1 mutations were characterized by histological grade III (55.6%) and higher Ki-67 index (Ki-67 ≥ 30%, 78.9%) compared with patients with BRCA2 mutations (27.8%, 58.2%). BRCA1 mutation patients accounted for a significantly higher proportion of triple negative breast cancer than BRCA2 mutation patients (71.1% vs 19.0%, P < 0.0001). A total of 142 (84.0%) patients received neo/ adjuvant chemotherapy, including anthracycline and/or taxane-based regimens (55.6%) or platinum-based regimens (27.2%). Median follow-up was 33.2 months. Three-year DFS (disease-free survival) and DRFS (distant recurrence-free survival) had no significant differences between patients with BRCA1 and BRCA2 mutations (82.0% vs 85.4%, P = 0.35; 94.3% vs 94.6%, P = 0.39). The 3-year DFS rate in BRCA1 mutation cohort of patients received platinum regimen was significantly higher than patients received nonplatinum regimen (96.0% vs 75.2%, P = 0.01). No differences between DFS and DRFS were observed in patients with BRCA2 mutation received platinum regimen and non-platinum regimen. Conclusion: Similar survival outcomes were observed in early breast cancer patients with BRCA1 and BRCA2 mutation, though they had different biological characteristics. Patients with BRCA1 mutations are more benefit from platinum-regimen. The value of platinum-regimen for early breast cancer patients with BRCA1 and BRCA2 needs to be verified further.Plain Language Summary: BRCA pathogenic mutation has been the principal genetic cause of breast cancer. Since the majority of studies have focused on the clinical manifestation and survival of patients with BRCA mutations and the wild type, few studies gave a concern about the survival outcome of breast cancer patients with BRCA1 and BRCA2 mutation. We aimed to compare the survival outcomes and efficacy of platinum between early breast cancer patients with BRCA1 and BRCA2. Our results showed that patients with BRCA1 and BRCA2 mutations had different biological characteristics, but similar survival outcomes in the early stages. Patients with BRCA1 mutations are more sensitive to platinum therapy in neoadjuvant settings.

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges

“…In contrast, germline mutations are inherited changes that affect reproductive cells and are present in all somatic cells; they may be common or rare in a given population. Of note, not only are somatic variants important for cancer treatment and mainly used as molecular targets, but germline mutations may also contribute, at least in part, to tumor development, progression, and resistance ( Chen X et al, 2023 ; Wang et al, 2023 ).…”