Introduction: Breast cancer is the most common malignancy affecting women. Cyclin D1 overexpression is one of the basic genetic alterations which implicated in its carcinogenesis. PD-L1 acts as a promising biomarker emerging in several tumor types.
Aim: To evaluate the immunohistochemical (IHC) expression of cyclin D1 and PD-L1 in invasive ductal carcinoma of the breast of no special type (IDC-NST) in different molecular subtypes, and to analyze the correlation between their expression with stromal tumor-infiltrating lymphocytes (TILs) density and response to neoadjuvant chemotherapy (NAC).
Materials and Methods: This prospective study was conducted in Faculty of Medicine, Zagazig University, Egypt. A total of 80 patients diagnosed with IDC-NST were studied from January 2017 to May 2019. Specimens taken were 30 core biopsies before receiving NAC protocol, and 50 mastectomy specimens not received NAC. Data was statistically analyzed using SPSS 22.0 software.
Results: PD-L1 expression was detected in 30.1% in tumor cells and in 22.5 % in TILs. There was a significant association between PD- L1 expression and stromal TILs (p<0.001).TILs density was high in 47.5 % of the cases mainly in triple-negative breast cancer. Cyclin D1 expression was observed in 56.3%. There was a significant association between PD-L1 expression and TNBC, and a significant association between luminal breast cancer and cyclin D1 expression. PD-L1 and cyclin D1 expression was significantly correlated with response to NAC.
Conclusion: Cyclin D1 and PD-L1 may act as predictive biomarkers for response to neoadjuvant chemotherapy and can be targeted in future therapeutic approaches.
Breast cancer; Cyclin D1; PD-L1; Tumor-infiltrating lymphocytes; Neoadjuvant chemotherapy
Breast cancer is the most common malignancy affecting women worldwide . PD-L1 is T-lymphocyte-inhibitory molecule and a member of the B7 family, several investigations have recently demonstrated that PD-L1 expression may have a key role in the interaction of tumor cells with the host immune response, and may function as a mechanism of adaptive immune resistance . PD-L1 is expressed in both tumor cells and TILs . PD-L1 acts as a promising biomarker emerging in several tumor types; patients whose tumors overexpress PD-L1 by immunohistochemistry (IHC) have improved clinical outcomes with anti-PD-L1 directed therapy . Many previous studies reported that breast cancers have unregulated PD-L1 on the tumor cell surface [3,5,6]. TILs can predict a response to a given treatment. It can serve as an excellent surrogate for monitoring cancer response to treatments. Therefore, these are most useful when assessed before the initiation of treatment with NAC. Also, TILs are relevant in decision-making regarding immunotherapy selection in various solid tumor types . Some types of aggressive breast cancer do not respond to hormonal or targeted therapy such as triple negative breast cancer (TNBC). PD-L1 expression in TNBC has been shown to range from 40 to 65% in several studies . The mammalian cell cycle is driven by a complex interplay between cyclins and their associated cyclin dependent kinase (CDK) partners, and dysregulation of this process is one of the hallmarks of breast cancer. Cyclin D1, a cell cycle regulator that has a critical job in cell cycle progression from the G1 phase to the S phase through interaction with CDk4 and CDk6 . Cyclin D1 protein was recognized by IHC in around 65-70% of breast carcinoma in several studies .