Trop-2 expression in triple-negative breast cancer according to histological subtype: correlations with tumor infiltrating lymphocytes (TILs) and survival

Abstract Background: Trop-2 is a transmembrane calcium signal transducer highly expressed in multiple solid tumors including breast cancer. Limited data exist about associations between Trop-2 protein expression, clinicopathological characteristics and outcome in triple-negative breast cancers (TNBC). Given the approval of sacituzumab govitecan in unselected TNBC, its evaluation in other breast cancer settings and the emergence of other Trop-2 targeted antibody-drug conjugates, Trop-2 emerges as an important drug target in solid tumors. Methods: Trop-2-expression of patients with TNBC diagnosed between 2000-2017 at UZ Leuven was determined with IHC (ab227689, Abcam) (continuous and categorical variables, high 201-300, medium 100-200 and low <100 H-score). Associations of Trop-2-expression with age, BMI, germline BRCA status, tumor grade and size, histological subtype, lymphovascular invasion (LVI), presence of DCIS, nodal status, stromal TILs, androgen receptor (AR), standardized mitotic index, and outcome (invasive disease-free survival (iDFS), distant recurrence-free survival (D-RFi) and breast cancer-specific survival (BCSS)) were assessed. Associations with continuous variables were assessed by the Spearman correlation coefficient (ρ). Group differences were assessed by the Kruskal Wallis test for multiple groups or Mann-Whitney U test for two groups. Cox proportional hazards models were used to assess the association between Trop-2 expression and outcome. Results: Total of 658 patients with a median age at diagnosis of 53y (range 22-89y) were included, with median follow-up 9.6y. Low, medium and high Trop-2 expression was seen in 58.2%, 25.3% and 16.5% of cases. AR was positive in 25.5% of cases (10%-cutoff). Highest Trop-2 expression was observed in tumors with apocrine histology (median 180 score), and lowest expression in tumors with metaplastic histology (median 45 score) (p<.001). Higher Trop-2 expression was correlated with higher AR expression (10%-cutoff) (p=0.009), more presence of nodal involvement (p=0.016), associated DCIS (p=0.004) and LVI (p=0.006). Trop-2 expression was not associated with pathological complete response (pCR) observed in 22 of 64 patients treated with neoadjuvant chemotherapy (p=0.96). There was an iDFS events frequency of 199 out of 658 (30.2%). There was no correlation between Trop-2 expression and sTILs or outcome. Conclusion: In patients with TNBC in a large tertiary center, higher Trop-2 expression was correlated with apocrine histology, higher AR expression, more associated DCIS, more LVI and nodal involvement. There was no correlation between Trop-2 expression and sTILs or outcome. Citation Format: Hava Izci, Kevin Punie, Lise Waumans, Annouschka Laenen, Hans Wildiers, Freija Verdoodt, Christine Desmedt, Jan Ardui, Ann Smeets, Sileny Han, Ines Nevelsteen, Patrick Neven, Giuseppe Floris. Trop-2 expression in triple-negative breast cancer according to histological subtype: correlations with tumor infiltrating lymphocytes (TILs) and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 507.