Desenlaces oncológicos y seguridad del tratamiento neoadyuvante con y sin antraciclinas en cáncer de mama temprano y localmente avanzado HER-2 positivo en el Instituto Nacional de Cancerología.

Abstract

Introduction: Recent clinical trials have shown similar effectiveness between anthracycline-containing and non-anthracycline regimens in neoadjuvant treatment of early and locally advanced breast cancer with respect to pathological complete response (pCR) rates and event-free survival. This has motivated a trend toward progressive withdrawal of anthracyclines in this clinical setting, seeking to reduce adverse effects such as cardiotoxicity and myelotoxicity. However, there are no comparative studies between the two most currently used regimens, derived from the BERENICE and TRAIN-2 studies. Methods: An analytical retrospective observational study was conducted with patients diagnosed with early, locally advanced HER-2 positive breast cancer who started neoadjuvant chemotherapy with anthracyclines (Doxorubicin, Cyclophosphamide x 4, Taxane, Trastuzumab and Pertuzumab x 4 = AC-THP) and without anthracyclines (Carboplatin, Paclitaxel weekly, Trastuzumab and Pertuzumab for 6-9 cycles = TCbHP) treated at the National Cancer Institute between April 2020 and December 2024. Complete pathological response, as well as cardiac toxicity and neurotoxicity in both treatment arms, were evaluated in the initial analysis. Results: A total of 111 patients were included in whom neoadjuvant treatment with chemotherapy plus pertuzumab and trastuzumab were defined. 51 patients received AC-THP and 60 received TCbHP (89.6% received 6 cycles). There was no statistically significant difference in pCR between patients operated on in each arm. 58.3% received ACHTP and 60.4% in TCbHP (OR 1.08 95% CI 0.49-2.36 p = 0.84). A descriptive analysis showed a trend toward higher pCR in T3-T4, N+, and ER-positive patients compared to patients who received the anthracycline arm. The incidence of LVEF decline >10% with an absolute value <50% during the neoadjuvant phase was 9.8% and 3.3% in ACTHP vs TCbHP. Grade 2 neuropathy events were reported in 9.8% vs. 23.3% of patients receiving TCbHP, respectively. Conclusions: Despite using fewer cycles than those administered in the TRAIN-2 study (6 vs 9 cycles) in most patients, we found similar pCR rates between the anthracycline-free regimen and the anthracycline-containing regimen. It is perhaps still pertinent to discuss the risk-benefit of using an anthracycline-containing regimen in patients with HR+, T3-4, and N+, in addition to the usual considerations of cardiovascular risk factors. Cardiotoxicity events in the anthracycline arm were similar to those in the BERENICE study. We recorded fewer cases of grade 2 or higher neuropathy than in the TRAIN-2 study, possibly due to the reduced number of cycles received.