Discussion
neutropenia, toxicity, TNBC, hereditary mutations, tumors
RECURRENCE, NEUTROPENIA, DNA STRAND BREAK, DISEASE, ADVERSE EFFECTS, TUMORS
In the NACATRINE study, a phase II randomized clinical trial conducted at a single center in Brazil, the addition of carboplatin to an anthracycline and taxane-based NACT regimen was associated with a numerical but not statistically significant increase in the pCR rate. Survival data are immature and, so far, do not show differences between groups. The toxicity profile was favorable and comparable to previous data, with increased neutropenia rate and dose reductions. However, the incidence of severe adverse effects was low, and there was no difference in treatment interruption between the two groups.NACT remains the standard treatment for early-stage and locally advanced TNBC. Platinum cytotoxic agents (such as carboplatin) cause DNA strand breaks via cross-linkage of DNA strands, increasing their effectiveness in tumors with impaired DNA repair pathways, a finding commonly seen in TNBC as well as in patients with hereditary mutations such as BRCA or other homologous recombination pathways genes [Benefits in terms of pCR and survival outcomes have placed the Keynote-522 study protocol, containing polychemotherapy with carboplatin associated with the immunotherapy pembrolizumab, as the preferred regimen for the neoadjuvant treatment of stages II and III TNBC [Genetic diversity of germline variants in TNBC predisposition genes is unexplored in miscegenated populations, such as those living in Latin America [Our findings are comparable to the published literature in the field, considering that various randomized clinical trials consistently demonstrated increased clinical response and pCR rates using neoadjuvant carboplatin in TNBC. The relationship between the use of neoadjuvant carboplatin and long-term survival benefits has been considered a controversial issue in breast oncology, considering that many studies that demonstrated pCR gain did not show significant benefits in terms of DFS and OS. However, recently the BRIGHTNESS study was published [The present study adds to the growing body of evidence supporting carboplatin as a component of NACT in stage II–III TNBC. We acknowledge that our study has several limitations, including the absence of dose-dense chemotherapy given the lack of access to colony-stimulating factors (G-CSF) in the public health system of LMIC, the relatively small sample size and difficulties inherent to the lack of statistical power in a phase II study. Despite not crossing the threshold for statistical significance of 15%, we believe the increase in the pCR rate observed in this study can be considered clinically significant and congruent with other randomized clinical trials. Since carboplatin is a widely accessible treatment even in LMIC, with low cost and a known and manageable toxicity profile, we consider that it can be regarded as in most cases of patients with TNBC with an indication for NACT in current clinical practice.Our study has several qualities and opportunities, such as an adequate clinical-epidemiological description of the profile of patients with TNBC treated in a public health institution in a LMIC, in addition to providing results in terms of pathological response and survival outcomes that have diverse applicability, including for planning new clinical research initiatives. All patients included had samples collected for a well-structured biobank that will serve for translational research initiatives, given that identifying predictive biomarkers to better define subsets of TNBC patients who benefit from the addition of carboplatin remains an unmet need. Additionally, the study aimed to identify biomarkers associated with pCR, residual invasive disease after NACT, and recurrence, and we intend to publish these exploratory analyses in the future.