The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
BackgroundThe presence of tumour-infiltrating lymphocytes (TILs) is a favourable prognostic factor in patients with early breast cancer. Programmed cell death-1 (PD-1) and its ligand PD-L1 are associated with a variety of adverse features. The purpose of this study was to clarify the relationships between TILs, PD-1 and PD-L1 as well as their prognostic implications in early breast cancer.MethodsWe investigated 180 patients with breast cancer who received neoadjuvant chemotherapy and underwent subsequent surgery for stage II–III invasive breast carcinoma between 1999 and 2007. TIL expression was classified as low or high using a previously reported scoring model. PD-1 and PD-L1 expression levels were determined by immunohistochemistry. The correlation between PD-1 expression in TILs and PD-L1 expression in cancer cells was also investigated.ResultsHigher tumour grade was significantly correlated with PD-L1 expression in tumours (p<0.0001). PD-1 and PD-L1 expression levels were associated with tumour subtype and were highest in triple-negative tumours (p<0.0001). Furthermore, expression of each of PD-1 and PD-L1 was significantly correlated with higher TIL expression and pathological complete response (pCR) (p<0.0001). PD-L1 expression in cancer cells was significantly correlated with PD-1 expression in TILs (p=0.03). The correlations between pCR and expression of each of PD-L1 and PD-1 were not significant.ConclusionExpression of PD-L1 and PD-1 in early breast cancer is associated with higher TIL scores and pCR; conversely, expression of these proteins correlates with poor prognostic clinicopathological factors such as tumour grade and subtype. TILs, PD-1 and PD-L1 can potentially predict the response to treatment.
Purpose
We present the English version of The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition.
Methods
The JBCS formed a task force to update the JBCS Clinical Practice Guidelines, 2015 edition, according to Minds Handbook for Clinical Practice Guideline Development 2014. First, we set multiple outcomes for each clinical question (CQ). Next, quantitative or qualitative systematic review was conducted for each of the multiple outcomes, and the strength of recommendation for the CQ was taken into consideration during meetings, with the aim of finding a balance between benefit and harm. Finalized recommendations from each session were confirmed through discussion and voting at the recommendation decision meeting.
Results
The recommendations, the strength of recommendation and the strength of evidence were determined based on systemic literature reviews and the meta-analyses for each CQ.
Conclusion
The JBCS updated the Clinical Practice Guidelines for systemic treatment of breast cancer.
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