Abstract
Platinum salts are active against metastatic triple negative breast cancer (mTNBC), and biomarkers to predict their effectiveness are urgently needed. In recent years, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have emerged as prognostic biomarkers in many malignancies, but their predictive role in platinum-treated mTNBC patients remains unexplored. We performed a retrospective, single centre study to evaluate the association between baseline NLR or PLR and progression free survival (PFS) of mTNBC patients treated with platinum-based chemotherapy. As a control population, we analysed data from patients with hormone receptor-positive HER2-negative (HR+ HER2−) metastatic breast cancer. Among 57 mTNBC patients treated with the carboplatin-paclitaxel or carboplatin-gemcitabine combination, high NLR and PLR were associated with significantly lower PFS at both univariate and multivariable analysis. Conversely, we did not find a significant association between NLR or PLR and the PFS of 148 patients in the control population. Our findings suggest that the NLR and PLR are predictive of benefit from platinum-containing chemotherapy specifically in mTNBC patients. If validated in larger prospective studies, these easy-to-measure parameters could be combined with emerging predictive biomarkers, such as BRCA 1/2 mutations, to improve the selection of mTNBC patients more likely to benefit from platinum-based chemotherapy.
Highlights
We found for the first time an association between higher neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) and worse progression free survival (PFS) in metastatic triple negative breast cancer (mTNBC) patients receiving carboplatin-paclitaxel or carboplatin-gemcitabine, but not in a control population of HR+ HER2− patients treated with the same regimens
High neutrophils can be associated with systemic inflammation or immune suppression[30]; high platelets reflect systemic inflammation as well, but can be associated with increased metastatization of neoplastic cells via platelet clots[30,31,32]; low lymphocyte counts can be associated with impaired activation of adaptive immunity or poor nutritional status[33,34]
The association between clinical outcomes and NLR/PLR was stronger than in the case of individual cell counts. This is not surprising, since parameter combinations are more stable to changes in single parameters and may capture more aspects of the tumor-immune system interplay
Summary
The main objective of the study was to investigate the potential association between baseline NLR/PLR and clinical outcome. The primary clinical endpoint was PFS, as defined as the time between treatment initiation and disease progression or death from any cause. OS was a secondary endpoint, and was defined as the time between treatment initiation and death from any cause. Response was assessed every 3 ChT cycles, but tumor re-evaluation was anticipated in patients with worsening symptoms or other signs suggestive of progressive disease (PD). Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Measurable disease were evaluated clinically by measuring lesion diameters every three weeks
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