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

Abstract

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.

Investigation of the Effects and Mechanisms of Anticancer Action of a Ru(II)‐Arene Iminophosphorane Compound in Triple Negative Breast Cancer Cells

“…The most common treatments currently employed are based on chemotherapeutic agents used in neoadjuvant settings (administered prior to other interventions such as surgery or radiation). [2] Combination therapy (chemotherapeutics in conjunction with monoclonal antibodies, check-point inhibitors, growth factor receptor inhibitors or kinase inhibitors) are being explored in clinical trials, with 112 active trials currently being evaluated. [3] The most common treatment for moderate-to-high risk TNBC is sequential, dose-dense anthracycline-taxane (ACT) combination.…”

“…[7] We have recently reviewed the activity and potential of metal-based compounds as chemotherapeutics for TNBC including recent clinical trials (up to October of 2020). [8] In this review we report not only on platinum compounds (that as cross-linking DNA agents are meant to be efficacious for TNBCs with BCRA1/2 mutations [2,9] ) but on a number of other metals (mostly ruthenium, gold and palladium [8] ). We focused on examples of compounds that have been efficacious in vivo and their mechanisms studied (at least in a preliminary way).…”

“…Conventional hormone and HER‐2 targeted therapies commonly used in other breast cancer types, have not been very successful in the treatment of TNBCs. The most common treatments currently employed are based on chemotherapeutic agents used in neoadjuvant settings (administered prior to other interventions such as surgery or radiation) [2] . Combination therapy (chemotherapeutics in conjunction with monoclonal antibodies, check‐point inhibitors, growth factor receptor inhibitors or kinase inhibitors) are being explored in clinical trials, with 112 active trials currently being evaluated [3] .…”

Real-life analysis of neoadjuvant-therapy-associated benefits for pathological complete response and survival in early breast cancer patients - role of trastuzumab in HER2+ BC and platinum in TNBC

“…An apparent difference in the OS following neoadjuvant treatment between TNBC patients with and without attaining pCR was shown in this study, with an aHR of 0.27 (CI: 0.15-0.51) for favoring the pCR population. Unfortunately, an increased chance of achieving pCR (adjusted OR: 2.60, CI: 1.59-4.26) following platinum-based therapy did not translate to a long-term survival benefit among both the pCR and non-pCR populations, despite great effort being made in this study to address the methodology concerns that have been raised in previous real-world studies (14)(15)(16)(17). That is, we adjusted for potential confounding effects attributable to patient baseline conditions using multivariate regression models and stratified the analyses by patients' pCR status to generate precise study estimates for the pCR and non-pCR populations separately.…”

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

“…After screening the title and abstract, there are only 39 publications were left for full-text review. After excluding 17 publications based on full-text analysis, 22 studies [ 8 , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] ] remained for qualitative and quantitative analysis, containing 18% (392/2158) of patients with a BRCA1/2 mutation. To further understand the significance of BRCA1/2 , 22 trials were separated into three phases: neoadjuvant, adjuvant, and progressed.…”