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.
Highlights
Escalation and de-escalation of treatments is of paramount importance in early breast cancer [1]
We focused on 999 ER+ HER2- early breast cancers, which were treated by hormonotherapy without chemotherapy
This study shows that systemic lymphocyte ratios, as measured in preoperative blood samples, can be reliable and inexpensive markers of disease recurrence in an unselected cohort of breast cancer patients
Summary
Escalation and de-escalation of treatments is of paramount importance in early breast cancer [1]. Traditional clinical and pathological features (i.e. nodal status, Ki67%, grading, etc.) are not always able to predict disease relapse, especially in ER+ early breast cancer [2, 3]. For this reason to predict the risk and address proper treatments can be challenging. In particular the density and spatial localization of CD8+ infiltrate within central core and invasive margins of tumor (evaluated by the Immunescore) are becoming important prognostic predictors, playing a role in the balance between tumor immune surveillance and escape [8]. Tumor-infiltrating lymphocytes (TILs) support antitumor cytotoxic response and are favorable prognostic features along with low densities of immunosuppressive elements like neutrophils and myeloidderived suppressor cells [9, 10]
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