Variable Expression of the Disialoganglioside GD2 in Breast Cancer Molecular Subtypes

SIMPLE SUMMARY: GD2 is an antigen that is tumor-specific and can be used as a target for specific immunotherapies. Since the knowledge about GD2 in breast cancer is limited, we analyzed the frequency of GD2 expression in breast cancer using two different staining methods and the impact of GD2 expression on the survival of breast cancer patients. GD2 expression was found in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. GD2 expression was not significantly associated with patient outcome. Unlike previous studies with smaller sample sizes that lacked correlation with clinical data, this study includes a larger cohort and associations with survival data and shows that GD2 is expressed on human breast cancer cells, providing a potential target for immunotherapies (e.g., anti-GD2 antibodies or GD2 CAR T cells), that are currently undergoing clinical testing. ABSTRACT: The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC (n = 568) and IF (n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.