Correlation of Trop-2 expression with clinicopathological characteristics, sTILs, AR expression and outcome in primary TNBC.

Abstract

e12558 Background: Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer highly expressed in multiple tumor types including breast cancer. Trop-2 overexpression is associated with poor survival. Given the approval of sacituzumab govitecan in advanced triple-negative breast cancer (TNBC), Trop-2 emerges as an important target for antibody-drug conjugates. Limited data exist about correlations of Trop-2 expression with clinicopathological characteristics and outcome in early TNBC. Methods: We included 127 patients with early TNBC, treated with primary surgery at UZLeuven from 2005-2017. Trop-2 expression was determined with IHC (ab227689, Abcam) on whole slide tumor sections from resection specimens and assessed as continuous (H-score 0-300) and categorical (high 201-300, medium 100-200 and low < 100) variables. Stromal tumor infiltrating lymphocytes (sTIL; low, intermediate and high), mitotic score and androgen receptor (AR) expression (1% or 10%-cutoff) were scored. We assessed associations between Trop-2 expression and age, BMI, BRCA status, tumor grade and size, lymphovascular invasion (LVI), DCIS, nodal status, sTILs, AR, mitotic index and outcome (Invasive disease free survival and breast cancer specific survival). Results: The median age at diagnosis was 51y (range 26-80y) and the median follow-up 8.5y. Low, medium and high Trop-2 expression was seen in 50%, 37% and 13% of cases. AR was positive in 32% of cases (10%-cutoff). Higher Trop-2 expression was correlated with age (ρ = 0.192, p = 0.03) and inversely correlated with mitosis/mm² (ρ = -0.2, p = 0.02). Patients with high Trop-2-expression were older compared to patients with low Trop-2-expression (median 58 vs 47 years, p = 0.02). LVI was more frequent in Trop-2-high (65%) compared to TROP-2-medium (15%) or -low (16%) (p < 0.001). Median mitosis/mm² was higher in Trop-2-low (14) compared to Trop-2-medium (10) and -high (8) (p = 0.004). Patients in Trop-2-high subgroup had more nodal involvement (53%) compared to Trop-2-medium (23%) and -low (21%) (p = 0.03). There was no correlation between Trop-2 expression and sTILs, AR or outcome. Conclusions: In this patient cohort with TNBC treated with upfront surgery, higher Trop-2 expression was correlated with older age, with more LVI and nodal involvement, while mitosis/mm² were higher in tumors with low Trop-2 expression. Trop-2 expression was not correlated with sTILs, AR or outcome. Limited numbers of events warrant caution in interpretation.