Thesis ( Ph.D.) - Cairo University - Faculty of National Cancer Institute - Department of Pathology

Although breast carcinoma had many targeted biomarkers for its treatment, it is a heterogenous disease with different outcomes and needs new markers especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. Programmed death-ligand 1 (PD-L1) is a new target with unclear role. The aim of this study was to examine the prevalence of PD-L1 in locally advanced invasive breast carcinoma and to elucidate its relation to tumor-infiltrating lymphocytes, breast carcinoma subtypes, established clinicopathological factors, pathological therapy response after neoadjuvant chemotherapy, disease-free survival and overall survival. Material and Methods: One hundred and five cases of locally advanced invasive breast carcinoma (stages IIB, IIIA, IIIB and IIIC) were evaluated for age, grade, tumor size, stage and node status (clinically before therapy and pathologically after therapy). The cases were retrieved immunohistochemically for estrogen receptor, progesterone receptor, Her2/neu and Ki-67. PD-L1 immunostaining was done and analyzed for all studied cases. Also, pretherapy tumor-infiltrating lymphocytes (TILs) density as well as TILs change after therapy were calculated and analyzed. Pathological therapy response was evaluated in all studied cases by different three pathological systems (Residual Cancer Burden, Miller-Payen grading system and Sataloff{u2019}s system). PD-L1 expression was correlated with pretherapy TILs density, TILs change, pathological therapy response, histopathological factors, breast cancer subtypes, 7-years DFS and overall survival. Results: PD-L1 was expressed in 32.4% of the studied cases. It was significantly associated with old age group, high grade tumors and high density (pretherapy) TILs. It was also expressed in a significant number of triple negative breast carcinoma (44.4%). PD-L1 negative breast cancer cases have better prognosis than those with PD-L1 positive breast cancer with statistically non-significant P value. There was no significant relation between PD-L1 and pathological therapy response, although, it revealed more expression in cases with complete therapy response. High change in TILs after therapy was strongly associated with complete and marked therapy response. Conclusion: Although the impact of PD-L1 on locally advanced breast cancer outcomes had not been clearly established, this result may provide evidence that PD-L1 is a bad prognostic and predictive marker. PD-L1 could be a new target for the treatment of patients with high grade breast carcinoma and TNBC group.

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