Neoadjuvant chemotherapy for HER2-positive breast cancer using dose-consolidated regimens and dual anti-HER2 blockade with pertuzumab and trastuzumab (preliminary results)

Abstract

The main goal of neoadjuvant chemotherapy (NACT) in aggressive breast cancer (BC) subtypes (triple-negative, HER2-positive) is to achieve complete pathological response (pCR), since it is associated with a significant decrease in the likelihood of recurrence and death. Currently, the standard approach for HER2+ BC stage II–III is NACT with the inclusion of a double anti-HER2 blockade, since this significantly increases the frequency of pCR. To date, it remains unclear whether the intensification of modern anthracycline-taxane-containing regimens of NACT affects the incidence of pCR in different BC subtypes, including HER2-positive, provided that a double anti-HER2 blockade is used.The aim of our prospective observational study from daily clinical practice was to assess the efficacy (according to the RCB system and the frequency of pCR) and tolerability of dose-dense NACT in stage II–III HER2-positive BC.Materials and methods. The study included 86 patients, mean age 45 years (26–74 years), in 96.5% of cases, the tumor was represented morphologically by invasive cancer of a nonspecific type, in 53.5% of the tumors had a positive luminal B HER2 phenotype, in 46.5% – non-luminal HER2+. The majority of patients (67.4%) had locally advanced inoperable breast cancer; in 80.2% of cases, metastatic lesions of regional lymph nodes were determined. NACT included anthracyclines and taxanes: four cycles of AC in a dose-dense regimen (once every 2 weeks), then four cycles of docetaxel 75 mg/m2 once every 3 weeks + trastuzumab + pertuzumab.Results. The frequency of pCR = RCB0 in the entire group was 54.7% (47/86), in locally advanced breast cancer – 55.9%, in operable breast cancer – 51.9%. In the luminal HER2+ subtype, the frequency of pCR was lower than in the non-luminal HER2+ subtype – 43.5% vs 67.5%, however, the differences were statistically insignificant (p = 0.09). The frequency of RCB0–I in ER+ HER2+ subtype was 60.9%, as in ER-HER2+ – 80%. Conclusions. In our study, for the first time, the efficacy of dose-dense NACT in HER2+ breast cancer was assessed; it was shown that the frequency of pCR and RCB0–I correspond to those in standard anthracycline-taxane-containing regimens. In the context of the use of double anti-HER2 blockade, the anthracycline stage, most likely, does not need to be escalated, since this does not lead to an increase in the frequency of complete pathomorphological regressions.