Carcinomas de mama invasores pré e pós-quimioterapia neoadjuvante e impacto na sobrevida global

Abstract

Purpose: Well-validated clinical and pathological predictors are needed to support therapeutic decisions so that patients receive individualized treatment with the greatest chance of benefit from neoadjuvant chemotherapy (NACT). NACT can change invasive breast carcinomas (IBC) and influence decisions on adjuvant treatments. We aimed to identify factors that might predict the level of tumor response by residual cancer burden class (RCB) to NACT, identify tumor changes and to verify their association with patient’s overall survival time (OS). Materials and methods: One hundred and five invasive breast carcinomas treated with NACT between 2008 and 2018 were studied and compared histological and immunohistochemical (IHC) parameters of pre- and post-NACT IBC samples and associated them with OS. Results: After NACT, most tumors had pathological partial response (89; 84.8%) and 16 tumors (15.2%) had pathological complete response (pCR), which had a lower risk of death (HR 0.27; CI: 0.11-0.68; p = 0.006). The following parameters were associated with the RBC class: tumor size, with a predominance of cT4 in the RBC III and cT3 in the others (p=0.011); regional lymph nodes, where only RCB II had N0 patients (p<0.001); tumor infiltrated inflammatory cells, with a predominance of high index only in RCB 0/1 (p=0.018); and IHC expression for TCD8+ lymphocytes, where only in RCB II low expression predominated (p=0.016). The independent prognostic factors showing higher risk of death were family history of breast cancer (HR 3.16; p=0.003), RCB class III (HR 8.77; p<0.001) and grade II (HR 3.07; p = 0.015) or grade III (HR 3.97; p=0.005). Changes were found in tumor nuclear pleomorphism (p=0.025); mitotic count (p=0.002); tumor-infiltrating inflammatory cells (p=0.016); in situ carcinoma (p=0.001); lymphovascular invasion (LVI; p=0.002); and expression of estrogen (p=0.003) and progesterone receptors (p=0.019); and Ki67 (p=0.003). Twenty-six tumors (30.2%) changed the IHC profile (p=0.050). Characteristics associated with a higher risk of death were: pre-NACT histological grade III (hazard ratio, HR, 2.94; p=0.007), high nuclear pleomorphism (HR: 2.53; p=0.036) and high Ki67 index (HR: 2.47; p<0.001); post-NACT LVI (HR 1.90; p=0.016) and Luminal B-like profile (HR: 2.58; p=0.031). Also, pre- (HR 2.26; p=0.011) and post-NACT (HR 2.12; p=0.038) intermediate mitotic count, pre- (HR: 4.45; p<0.001) and post-NACT (HR: 4.52; p<0.001) triple-negative IHC profile. Associations with lower risk were: pre- (HR: 0.35; p<0.001) and post-NACT (HR: 0.39; p<0.001) ER positive, and pre- (HR: 0.37; p<0.001) and post-NACT (HR: 0.57; p=0.044) PR positive. Changes in IHQ profile were associated with longer OS (p=0.050). In multivariate analysis, pre-NACT grade III and pre-NACT and post-NACT triple negative IHC profile proved to be independent factors for shorter OS. Conclusion: Family history of breast cancer, RCB classes and histological grade are independent prognostic factors. Clinical staging, presence of inflammatory infiltrate and intratumoral TCD8 lymphocytes were predictors of RCB classes. Tumor characteristics and biomarkers can change after NACT with an impact on OS, therefore they should be reassessed on residual samples to improve therapeutic decisions.