Editor’s Note: Patients carrying BRCA gene mutations face a significantly increased risk of developing breast cancer, and conventional therapies often yield suboptimal results. PARP inhibitors, by leveraging the mechanism of synthetic lethality, precisely target BRCA-mutated tumor cells. After achieving breakthroughs in advanced breast cancer, PARP inhibitors are now expanding into the early-stage setting. At the 2025 CSCO Annual Meeting, Professor Wei Li from Jiangsu Provincial People’s Hospital delivered a presentation titled ‘Precision Targeting: The Role of PARP Inhibitors in BRCA-Mutated Breast Cancer.’ In her talk, she reviewed the latest advances in the clinical application of PARP inhibitors among BRCA-mutated breast cancer patients. Following the conference, Oncology Frontier invited Professor Li to discuss the clinical value and safety profile of PARP inhibitors in early-stage disease, optimization of future treatment strategies, and the current challenges and opportunities in BRCA genetic testing in China.
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Oncology Frontier: PARP inhibitors have demonstrated remarkable efficacy in BRCA-mutated breast cancer. From your perspective, what is the most important clinical significance of applying PARP inhibitors in early-stage BRCA-mutated patients? What safety considerations should clinicians keep in mind during treatment?
Professor Wei Li: PARP inhibitors have shown impressive efficacy not only in advanced BRCA-mutated breast cancer but also in the early-stage setting. A landmark study in this field is the OlympiA trial, which enrolled 1,836 patients with germline BRCA mutations (gBRCAm) and high-risk early-stage breast cancer (either HR+/HER2– or triple-negative subtypes). After completing standard (neo)adjuvant and local therapies, patients were randomized 1:1 to receive olaparib (300 mg) or placebo to evaluate efficacy and safety. After six years of follow-up, the olaparib group achieved a 9.4% improvement in invasive disease-free survival (iDFS) compared with placebo (79.6% vs. 70.3%; HR 0.65, 95% CI: 0.53–0.78). At the four-year mark, the absolute difference in iDFS was 8.4%. Long-term follow-up further confirmed sustained survival benefits. In the intention-to-treat population, olaparib also significantly improved distant disease-free survival (DDFS) — six-year DDFS rates were 83.5% vs. 75.7%, with an absolute benefit of 7.8% (HR 0.65, 95% CI: 0.53–0.81). For overall survival (OS), the olaparib arm achieved a six-year OS rate of 87.5%, compared with 83.2% in the placebo arm (HR 0.72, 95% CI: 0.56–0.93), confirming a meaningful improvement in long-term survival outcomes. For early breast cancer, the treatment goal differs from that of advanced disease — we aim to minimize recurrence and prolong survival through comprehensive systemic therapy. For patients with BRCA mutations, the addition of a PARP inhibitor further strengthens disease control and survival outcomes. Therefore, in high-risk early-stage patients with confirmed BRCA mutations, PARP inhibitors represent a clinically valuable and evidence-based option. In terms of safety, PARP inhibitors are generally well-tolerated. The most common adverse events include hematologic toxicities (such as anemia) and gastrointestinal reactions, but these are typically mild to moderate and manageable. Most patients maintain good adherence, making PARP inhibitors an effective and safe treatment choice for early-stage breast cancer.
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Oncology Frontier: Despite the proven benefits of PARP inhibitors, challenges remain in optimizing their clinical application. What areas of research should be prioritized to further refine treatment strategies?
Professor Wei Li: The application of PARP inhibitors is a continuum evolving from advanced to early disease. We hope future studies can expand their benefit to broader patient populations. For example, beyond germline or somatic BRCA1/2 mutations, it remains to be determined whether patients exhibiting ‘BRCAness’ characteristics — those with homologous recombination deficiency (HRD) but no BRCA mutation — could also benefit from PARP inhibition. Another promising direction is combination therapy. Studies are exploring PARP inhibitors in combination with immunotherapy, chemotherapy, antiangiogenic agents, and other targeted therapies. These combinations may help overcome resistance mechanisms and further improve efficacy. Continuous exploration of synergistic strategies will be key to enhancing outcomes for BRCA-mutated and HRD-positive patients in the future.
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Oncology Frontier: Precision medicine depends on precise testing. How would you describe the current state of BRCA genetic testing in China? What steps are needed to improve accessibility, standardization, and result interpretation?
Professor Wei Li: Indeed, precision therapy begins with precision diagnostics. Ideally, all patients who meet criteria should undergo genetic testing. However, current data show that the majority of patients have not yet been tested. Key challenges include limited access to testing, cost barriers, and lack of standardized methodologies. Additionally, some patients still have insufficient awareness of the availability and importance of genetic testing. To address these issues, public education must be strengthened to raise awareness of genetic testing and its clinical implications. At the same time, it is crucial to establish standardized testing workflows and ensure accurate interpretation of results, so that clinicians can base treatment decisions on reliable molecular data. We also hope that genetic testing will gradually be incorporated into national insurance coverage, improving affordability and enabling more patients who need testing to benefit from precision oncology.
Professor Wei Li Deputy Director, Breast Center Jiangsu Provincial People’s Hospital
