الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Globally, breast cancer is the second most frequently diagnosed malignancy just behind lung cancer, accounting for over two million cases each year, and the fourth cancer causing death worldwide; the leading cause of cancer death though in females, with around 600,000 deaths each year (Bray et al., 2018).
Cancer immunotherapy through the inhibition of negative immune regulators, or checkpoints, represents a major milestone in cancer therapy. Of the most common immune checkpoints to be targeted is the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). The measurement of these two biomarkers is used as a prognostic and predictive marker to the cancer immunotherapy with checkpoint inhibitors (Zerdes et al., 2018).
Inhibitors of PD-1 and PD-L1 have been shown to significantly improve patient outcomes in different types of immunogenic cancers such as non-small cell lung cancers (NSCLC), malignant melanoma, renal cell carcinoma (RCC), and some immunogenic breast cancer subtypes (Li & Gu, 2018; Schmid et al., 2018; Wang et al., 2017; Zhou et al., 2018).
Breast cancer is composed of heterogenous subtypes, each has its specific pathologic and genetic characters, as well as different prognostic significance. Of these subtypes, triple negative breast cancer (TNBC) is the most immunogenic type, as it is rich in tumor infiltrating lymphocytes and PD-L1 co-expression (Sobral-Leite et al., 2018).
In a phase III trial, combining atezolizumab and nab-paclitaxel conferred a non-statistically significant overall survival (OS) benefit compared with nab-paclitaxel alone in unselected, patients with TNBC. Interestingly, the difference in OS was statistically and clinically significant in the PD-L1 positive subgroup of patients, highlighting the potential clinical importance of PD-L1 expression as a predictive biomarker in breast cancer (Schmid et al., 2018).
We aimed to evaluate the prognostic value of PD-L1 expression and associated tumor infiltrating lymphocytes in stage IV breast cancer patients, and correlate them with response evaluation, progression free survival and overall survival.
We found that high TIL counts infiltrating the breast tumor is associated with worse OS and PFS in patients with metastatic breast cancer. High PD-L1 expression was significantly associated with high TIL levels.
Regarding the previous published data, there is a major controversy about the prognostic value of TIL and PD-L1 in breast cancer. TNBC and Her2 enriched are the most common types associated with TIL infiltration and PD-L1 positivity (on tumor cells and TILs), and this renders them more immunogenic than other subtypes. This is especially important in TNBC because of the lack of any targeted therapeutic solution other than chemotherapy. Further studies are warranted to determine the predictive value of PD-L1 positivity and TIL infiltration regarding the response to immunotherapy.