Abstract P4-06-13: Programmed death-1 and programmed death-ligand 1 expression in sporadic breast cancer compared to BRCA germline mutation related breast cancer and male breast cancer
Authors: Manson QF , ter Hoeve ND , Moelans CB , van Diest PJ 
Published: May 2019

Introduction Programmed death 1 (PD-1) and its ligand PD-L1 seem to have a prognostic and predictive role in a variety of cancer types, especially the ones with a high mutational load and immunogenic profile. Despite that breast cancer is not considered as immunogenic, recent studies suggested that PD-1 and PD-L1 do have a prognostic and/or predictive value in breast cancer, which varies between molecular subtypes. However, the role of PD-1 and PD-L1 in BRCA germline mutation related breast cancer and male breast cancer has not yet been examined. We therefore evaluated the expression of PD-1 and PD-L1 in sporadic, BRCA related and male breast cancer.

Methods Tissue microarrays were constructed of formalin-fixed paraffin-embedded resection material from 257 sporadic, 132 BRCA related and 175 male breast cancer patients and stained for PD-1 and PD-L1 by immunohistochemistry. Expression in BRCA related and male breast cancer was compared to the sporadic group and correlations with clinicopathological features were tested.

Results PD-1 and/or PD-L1 expression was available for 245 sporadic, 145 male and 103 BRCA related breast cancers. PD-1 expression in the BRCA group was significantly higher than in the sporadic group (79.0% vs 64.1%), this in contradictory to the male group, where PD-1 was significantly less often expressed than in the sporadic group (46.9% vs. 64.1%). For PD-L1 expression no significant differences were seen between the groups. In subgroup analysis PD-1 expression was higher in grade 3 tumors compared to the lower grade tumors, which was significant in sporadic and male breast cancer. For PD-L1 a significantly higher expression was observed in grade 3 tumors in BRCA related breast cancer, while a significantly lower expression in grade 3 tumors was seen in the sporadic subgroup. No differences were observed looking at PD-(L)1 expression and molecular subtype.

Subgroup analysis for PD-1 and PD-L1 expression and tumor grade  Grade PD-1 negative, No. (%) PD-1 positive, No. (%) P-value PD-L1 negative, No. (%) PD-L1 positive, No. (%) P-value Sporadic116 (39.0)25 (61.0) 20 (52.6)18 (47.4)  237 (43.5)48 (56.5) 0.03740 (50.0)40 (50.0) 0.036 330 (26.5)83 (73.5) 68 (68.0)32 (32.0) BRCA1-1 (100) -1 (100)  28 (34.8)15 (65.2)0.18620 (87.0)3 (13.0) 0.011 313 (17.3)62 (82.7) 46 (61.3)29 (38.7)  Male120 (64.5)11 (35.5) 20 (64.5)11 (35.5)  228 (58.3)20 (41.7) 0.03733 (66.0)17 (34.0)0.213 324 (39.3)37 (60.7) 31 (50.8)30 (49.2) 

Conclusion PD-1 expression is higher in BRCA related breast cancer compared to sporadic breast cancer, but lower in male breast cancer. Additionally, PD-1 expression is more frequent in grade 3 tumors. Patients with BRCA related breast cancer might therefore respond better to PD-1 inhibitors than patients with sporadic breast cancer, this in contrast to men with breast cancer.

Citation Format: Manson QF, ter Hoeve ND, Moelans CB, van Diest PJ. Programmed death-1 and programmed death-ligand 1 expression in sporadic breast cancer compared to BRCA germline mutation related breast cancer and male breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-13.