Efficacy of platinum in advanced triple-negative breast cancer with germline BRCA mutation determined by next
Nan Wang1, Kun Li1, Wenfa Huang1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Objective:
To compare the efficacy of platinum- and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer (TNBC) and analyze the relationship between their efficacy and BRCA gene status.
Methods:
Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology, Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy. A total of 114 patients had BRCA1/2 gene tested by next generation sequencing (NGS) using peripheral blood, and we analyzed the correlation between their efficacy and BRCA1/2 gene status.
Results:
Non-platinum-based chemotherapy (NPCT) was administered to 129 and platinum-based chemotherapy (PBCT) to 91 study patients. The clinical benefit rate (CBR) and median progression-free survival (PFS) were not statistically different between NPCT and PBCT groups. The median overall survival (OS) was 30.0 and 22.5 months for PBCT and NPCT group, respectively [P=0.090, hazard ratios (HR)=0.703]. BRCA status was assessed in 114 patients, 14 of whom had deleterious germline BRCA1/2 (gBRCA) mutations (seven in each group). In PBCT group, the CBR was 85.7% and 35.1% for patients with and without deleterious gBRCA mutations, respectively (P=0.039). The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious gBRCA mutations, respectively (P=0.001, P=0.161, respectively). Patients in PBCT group had significantly greater rates of grade 3-4 anemia (5.5%vs. 0%) and thrombocytopenia (8.8% vs. 0%), whereas palmar-plantar erythrodysesthesia (12.4% vs. 0%) and peripheral neuropathy (8.6% vs. 1.1%) occurred more frequently in NPCT group.
Conclusions:
Platinum-based regimens are more effective in patients with deleterious gBRCA mutations, but no difference in patients without BRCA gene mutations, so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect. And we recommend that patients with advanced TNBC should have BRCA gene test.
Insights
Platinum-based chemotherapy shows improved outcomes for advanced triple-negative breast cancer (TNBC) patients with BRCA mutations. Genetic testing for BRCA is recommended for advanced TNBC patients to guide treatment selection.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Advanced triple-negative breast cancer (TNBC) presents a significant therapeutic challenge.
- Treatment efficacy varies based on genetic mutations, particularly BRCA.
- Identifying optimal first-line treatments for advanced TNBC is crucial.
Purpose of the Study:
- To compare platinum-based chemotherapy (PBCT) versus non-platinum-based chemotherapy (NPCT) for advanced TNBC.
- To analyze the efficacy of these regimens in relation to BRCA gene status.
- To guide personalized treatment strategies for advanced TNBC.
Main Methods:
- Retrospective analysis of 220 advanced TNBC patients treated from 2013-2018.
- Evaluation of chemotherapy efficacy, including clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS).
- BRCA1/2 gene testing using next-generation sequencing (NGS) in 114 patients.
Main Results:
- No significant difference in CBR or PFS between PBCT and NPCT overall.
- PBCT demonstrated improved median overall survival (OS) compared to NPCT (30.0 vs. 22.5 months).
- Patients with deleterious germline BRCA mutations (gBRCA) showed significantly higher CBR and PFS with PBCT compared to those without gBRCA mutations.
Conclusions:
- Platinum-based regimens are more effective in advanced TNBC patients with deleterious gBRCA mutations.
- Non-platinum regimens are a viable option for patients without BRCA mutations, considering toxicity.
- BRCA gene testing is recommended for all advanced TNBC patients to inform treatment decisions.
