A new prognostic model including immune biomarkers, genomic proliferation tumor markers (AURKA and MYBL2) and clinical-pathological features optimizes prognosis in neoadjuvant breast cancer patients

Esmeralda García-Torralba; Esther Navarro Manzano; Gines Luengo-Gil; Pilar De la Morena Barrio; Asunción Chaves Benito; Miguel Pérez-Ramos; Beatriz Álvarez-Abril; Alejandra Ivars Rubio; Elisa García-Garre; Francisco Ayala de la Peña; Elena García-Martínez

doi:10.3389/fonc.2023.1182725

A new prognostic model including immune biomarkers, genomic proliferation tumor markers (AURKA and MYBL2) and clinical-pathological features optimizes prognosis in neoadjuvant breast cancer patients

Front Oncol. 2023 May 29:13:1182725. doi: 10.3389/fonc.2023.1182725. eCollection 2023.

Authors

Esmeralda García-Torralba^{1

2

3}, Esther Navarro Manzano^{2

3}, Gines Luengo-Gil^{1

2

3}, Pilar De la Morena Barrio^{1

2

3}, Asunción Chaves Benito⁴, Miguel Pérez-Ramos⁴, Beatriz Álvarez-Abril^{1

2

3}, Alejandra Ivars Rubio^{1

2

3}, Elisa García-Garre^{1

2

3}, Francisco Ayala de la Peña^{1

2

3}, Elena García-Martínez^{1

2

3

5}

Affiliations

¹ Department of Haematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain.
² Department of Medicine, Medical School, University of Murcia, Murcia, Spain.
³ Instituto Murciano de Investigación Biosanitaria (IMIB), Murcia, Spain.
⁴ Department of Pathology, University Hospital Morales Meseguer, Murcia, Spain.
⁵ Medical School, Catholic University of Murcia, Murcia, Spain.

Abstract

Background: Up to 30% of breast cancer (BC) patients treated with neoadjuvant chemotherapy (NCT) will relapse. Our objective was to analyze the predictive capacity of several markers associated with immune response and cell proliferation combined with clinical parameters.

Methods: This was a single-center, retrospective cohort study of BC patients treated with NCT (2001-2010), in whom pretreatment biomarkers were analyzed: neutrophil-to-lymphocyte ratio (NLR) in peripheral blood, CD3+ tumor-infiltrating lymphocytes (TILs), and gene expression of AURKA, MYBL2 and MKI67 using qRT-PCR.

Results: A total of 121 patients were included. Median followup was 12 years. In a univariate analysis, NLR, TILs, AURKA, and MYBL2 showed prognostic value for overall survival. In multivariate analyses, including hormone receptor, HER2 status, and response to NCT, NLR (HR 1.23, 95% CI 1.01-1.75), TILs (HR 0.84, 95% CI 0.73-0.93), AURKA (HR 1.05, 95% CI 1.00-1.11) and MYBL2 (HR 1.19, 95% CI 1.05-1.35) remained as independent predictor variables.

Conclusion: Consecutive addition of these biomarkers to a regression model progressively increased its discriminatory capacity for survival. Should independent cohort studies validate these findings, management of early BC patients may well be changed.

Keywords: Breast cancer; neoadjuvant chemotherapy; neutrophil-to-lymphocyte ratio; proliferation markers; tumor-infiltrating lymphocytes.

Grants and funding

This work was supported by the Ana Balil-GEICAM grant (Spanish Breast Cancer Research Group); the funding institution has not participated in collecting, analyzing, or interpreting the data, nor did it participate in drafting this manuscript. This work was also supported by Instituto de Salud Carlos III (PI12/02877), including FEDER funding by the European Union. ENM was funded by the Ministerio de Educación, Cultura y Deporte [Ministry of Education, Culture, and Sports] (Spain) [FPU16/06537]. This work was also partially funded by two research-funding initiatives: “Calasparra se mueve”, inspired by women from Calasparra (Murcia), Spain, and “Pulseras solidarias”, Cieza (Murcia), Spain. The sponsors have in no way been involved in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. BIOBANC-MUR is supported by the Instituto de Salud Carlos III (project PT20/00109), by the Instituto Murciano de Investigación Biosanitaria, IMIB and by the Consejeria de Salud de la Comunidad Autónoma de la Región de Murcia [the regional healthcare authority for the Autonomous Community of Murcia].