Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence

Simple Summary Neoadjuvant chemotherapy (NACT) is the standard treatment for early-stage triple-negative breast cancer (TNBC). Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. The administration of NACT regimens with platinum salts is associated with a higher pCR rate. However, with unclear treatment guidelines and at the expense of a higher incidence of adverse events. Identifying patients and circumstances in which the benefits of platinum NACT outweigh inconveniences is still an ongoing challenge. Considering early clinical response (ECR) after the initial standard NACT cycles together with other suitable predictors could be useful to decide about the administration of platinum salts in clinical practice. The results of this large single institutional retrospective study of consecutive patients showed the significant role of adding platinum salts in older patients with high-proliferative early responded tumors and persisted lymph nodes involvement regardless of BRCA1/2 status. Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 >= 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders >= 45 years, Ki-67 >= 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders' survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.

Automated summary

Neoadjuvant chemotherapy is a standard treatment for early-stage TNBC, with achieving pCR being a key factor for favorable outcomes. Platinum salts in NACT are linked to higher pCR rates but come with unclear guidelines and increased adverse events. Identifying patients who benefit from platinum NACT remains a challenge.