Breast Cancer: Targets and Therapy (Jan 2021)
Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment
Abstract
Jesse Lopes da Silva,1 Fabiana Resende Rodrigues,2 Guilherme Gomes de Mesquita,2 Priscila Valverde Fernandes,2 Luiz Claudio Santos Thuler,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil; 2Pathology Department, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da SilvaDivision of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), 37 André Cavalcanti Street - 6th Floor - Annex Building, Downtown, Rio de Janeiro, RJ 20231-050, BrazilTel +55-2132076585Email [email protected]: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC).Materials and Methods: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes.Results: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0– 1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥ 40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p < 0.0001, respectively) and LNR (p < 0.0001 and p < 0.0001, respectively) showed significant association.Conclusion: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.Keywords: triple-negative breast cancer, neoadjuvant chemotherapy, biomarkers, residual burden cancer, lymph node ratio
