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

Abstract

Purpose

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 non-platinum 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.

Keywords:

• breast cancer
• BRCA mutation
• survival outcome
• chemotherapy
• platinum

Institutional Review Board Statement

The retrospective study was reviewed and approved by the Institutional Review Board of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College (23/185-3927). All procedures were carried out in accordance with the Declaration of Helsinki.

Data Sharing Statement

The data presented in this study are available upon request from the corresponding author.

Informed Consent Statement

Informed consent has been obtained from the study participants prior to study commencement.

Acknowledgments

For their support and research assistance, I would like to thank the following professors who have contributed substantially to the completion of this study:

Prof. Qing Li, Prof. Qiao Li, Prof. Jiayu Wang, Prof. Ying Fan, Prof. Yang Luo, Prof. Peng Yuan, Prof. Fei Ma, Prof. Binghe Xu. They made a significant contribution to the work reported. The authors wish to thank all study participants who participated in this work.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no potential conflicts of interest.

Additional information

Funding

This research received no external funding.