Preoperative Systemic Inflammatory Biomarkers Are Independent Predictors of Disease Recurrence in ER+ HER2- Early Breast Cancer

Marta Truffi; Francesca Piccotti; Sara Albasini; Valentina Tibollo; Carlo Francesco Morasso; Federico Sottotetti; Fabio Corsi

doi:10.3389/fonc.2021.773078

Preoperative Systemic Inflammatory Biomarkers Are Independent Predictors of Disease Recurrence in ER+ HER2- Early Breast Cancer

Front Oncol. 2021 Nov 4:11:773078. doi: 10.3389/fonc.2021.773078. eCollection 2021.

Authors

Marta Truffi¹, Francesca Piccotti¹, Sara Albasini², Valentina Tibollo³, Carlo Francesco Morasso¹, Federico Sottotetti⁴, Fabio Corsi^{2

5}

Affiliations

¹ Nanomedicine and Molecular Imaging Lab, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.
² Breast Unit, Surgery Department, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.
³ Laboratory of Informatics and Systems Engineering for Clinical Research, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.
⁴ Medical Oncology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.
⁵ Department of Biomedical and Clinical Sciences "L. Sacco", Università di Milano, Milano, Italy.

Abstract

The host's immune system plays a crucial role in determining the clinical outcome of many cancers, including breast cancer. Peripheral blood neutrophils and lymphocytes counts may be surrogate markers of systemic inflammation and potentially reflect survival outcomes. The aim of the present study is to assess the role of preoperative systemic inflammatory biomarkers to predict local or distant relapse in breast cancer. In particular we investigated ER+ HER2- early breast cancer, considering its challenging risk stratification. A total of 1,763 breast cancer patients treated at tertiary referral Breast Unit were reviewed. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios were assessed from the preoperative blood counts. Multivariate analyses for 5-years locoregional recurrence-free (LRRFS), distant metastases-free (DMFS) and disease-free survivals (DFS) were performed, taking into account both blood inflammatory biomarkers and clinical-pathological variables. Low NLR and high LMR were independent predictors of longer LRRFS, DMFS and DFS, and low PLR was predictive of better LRRFS and DMFS in the study population. In 999 ER+ HER2- early breast cancers, high PLR was predictive of worse LRRFS (HR 0.42, p=0.009), while high LMR was predictive of improved LRRFS (HR 2.20, p=0.02) and DFS (HR 2.10, p=0.01). NLR was not an independent factor of 5-years survival in this patients' subset. Inflammatory blood biomarkers and current clinical assessment of the disease were not in agreement in terms of estimate of relapse risk (K-Cohen from -0.03 to 0.02). In conclusion, preoperative lymphocyte ratios, in particular PLR and LMR, showed prognostic relevance in ER+ HER2- early breast cancer. Therefore, they may be used in risk stratification and therapy escalation/de-escalation in patients with this type of tumor.

Keywords: disease recurrence; early breast cancer; lymphocyte ratios; predictive factors; systemic inflammatory biomarkers.