Triple-Negative Breast Cancer: Assessing the Role of Immunohistochemical Biomarkers on Neoadjuvant Treatment

Abstract

Objective

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

Acknowledgments

The authors are indebted to all patients and their families for their trust and participation and for the provision of biological material for research purposes. The authors wish to thank Mrs. Isabele Small for technical support with statistical analysis.

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethical Approval

The study was approved by the Ethics in Human Research Committee of INCA, Rio de Janeiro, Brazil, under registration number CAAE 61675516.9.0000.5274, and conducted in accordance with Good Clinical Practice guidelines.

Informed Consent

For this type of study with observational retrospective design with anonymized data analysis, the Institutional Review Board (Comitê de Ética em Pesquisa do Instituto Nacional de Câncer; CEP-INCA) decided in favor of waiving the consent form.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Jesse Lopes da Silva and Andreia Cristina de Melo received research funding from AstraZeneca. Andreia Cristina de Melo reports grants from AstraZeneca Brazil during the conduct of the study; grants, personal fees, and non -financial support from MSD, personal fees and non-financial support from BMS, grants from AstraZeneca, Novartis, Loreal Brazil, Libbs, and Zodiac, outside the submitted work. The authors report no other conflicts of interest in this work.