Dose-dense neoadjuvant chemotherapy of operable and locally advanced inoperable triple negative breast cancer: First results of single-centre prospective trial

Abstract

Introduction. Neoadjuvant chemotherapy (NACT) is the standard of care for II–III stages of TN BC. Complete pathomorphological response (pCR) is associated with a signifiant increase in event-free and overall survival. In addition, in the absence of pCR, post-neoadjuvant adjuvant therapy is prescribed, while if pCR is achieved, additional treatment is not carried out. Despite a large number of studies on NACT of TN BC, different NACT regimens in various clinical trials make it diffiult to interpret their results.Objective. To investigate the effiacy of 4ddAC followed by 12 weekly cycles of paclitaxel and carboplatin in TN BC (according to the RCB system and the frequency of pCR); determine the predictive factors for the effectiveness of this chemotherapy regimen, and the effect of dose intensity on the pCR rate.Methods. This prospective study included 154 patients with TN breast cancer who received dose-dence neoadjuvant chemotherapy from January 2017 to March 2022.Results. PCR rate was 53.25 % (n = 82), RCB 0–I was 66.88 % (n = 103), disease progression was observed in 3.25 % (n = 4). The frequency of germline mutations in the BRCA1/2 genes was 21.43 % (n = 33). The most common mutation was BRCA1 5382insC – 63.64 % (n = 21) of all BRCA1/2 mutations. Rare mutations detected by NGS accounted for 30.3 % (n = 10). The only factor associated with a signifiant increase in the pCR rate was age ≤50 years (p = 0.010), there was a trend towards an increase pCR rate in the subgroups T1–2 (p = 0.052) and BRCA1/2 mut (p = 0.080). There was no effect of the dose intensity on the achievement of pCR.Conclusions. This retrospective analysis is the largest study evaluating the effiacy of 4 ddAC followed by 12 PC in NACT TN BC. The regimen allows to achieve a high frequency of pCR, despite the large proportion of patients with locally advanced breast cancer. The high frequency of rare mutations in the BRCA1/2 genes and the potential therapeutic signifiance of this marker in residual disease treatment dictates the need for NGS in all patients with TN in breast cancer.