Abstract P4-07-16: Correlation of Trop-2 expression with clinicopathological characteristics and outcome in triple-negative breast cancer (TNBC)
Authors: Izci Hava , Punie Kevin , Waumans Lise , Laenen Annouschka , Wildiers Hans , Verdoodt Freija , Desmedt Christine , Ardui Jan , Smeets Ann , Han Sileny , Nevelsteen Ines , Neven Patrick , Floris Giuseppe 
Published: March 2022

Abstract
Purpose Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer highly expressed in multiple solid tumors including breast cancer. Trop-2 overexpression has been associated with poor survival, but limited data exist about the association between Trop-2 expression, clinicopathological characteristics and outcome in patients with TNBC. Given the approval of sacituzumab govitecan in unselected TNBC and its evaluation in other breast cancer settings, Trop-2 emerges as an important target for antibody-drug conjugates. Methods We included 470 patients with TNBC, treated with upfront surgery or upfront chemotherapy at the University Hospitals Leuven from 2000-2017. Trop-2 expression was determined with IHC (ab227689, Abcam) on whole slide tumor sections from resection specimens (upfront surgery group) or core needle-biopsy (upfront chemotherapy group) and assessed as continuous (H-score 0-300) and categorical (high 200-300, medium 100-200 and low &lt;100) variables. Stromal tumor infiltrating lymphocytes (sTIL; low, intermediate and high), mitotic score and androgen receptor (AR) expression (10%-cutoff) were scored. We assessed associations between Trop-2 expression and age, BMI (lean 18-25 (low), overweight 25-30 and obese ≥30 (high)), tumor grade and size, histological subtype, lymphovascular invasion (LVI), presence of DCIS, nodal status, sTILs, AR, standardized mitotic index and outcome (distant recurrence-free survival (DRFI), invasive disease-free survival (IDFS) and breast cancer-specific survival (BCSS)). Associations between continuous variables were assessed by the Spearman correlation coefficient (ρ). Cox proportional hazards models were used to assess the association between Trop-2 expression of tumor characteristics and outcome. Results are presented as hazard ratios (HR) with incremental increase of continuous Trop-2. Results The median age at diagnosis was 51y (range 22-85y) and the median follow-up 9.6y. For the group with upfront surgery (N=406), AR was positive in 21.5% of cases. Low, medium and high Trop-2 expression was seen in 55.7%, 23.6% and 20.7%. Higher Trop-2 expression was correlated with higher age at diagnosis (ρ=0.13, p=0.009). LVI was more frequent in Trop-2-high (39%) compared to Trop-2-medium (19%) or -low (20%) (p=0.004). Patients in Trop-2-high subgroup had more nodal involvement (45%) compared to Trop-2-medium (29%) (p=0.03). There was no correlation between Trop-2 expression with sTILs, BMI, AR or outcome. However, we found significantly improved DRFI and BCSS with increasing Trop-2 expression for the BMI-low subgroup (HR=0.95 [95%C.I. 0.89;0.99], p=0.02 and HR=0.95 [95%C.I. 0.89;0.99], p=0.04). For the group with upfront chemotherapy (N=64), AR was positive in 28.1% of cases. Low, medium and high Trop-2 expression was seen in 45.3%, 53.1% and 1.6% of cases. No difference was seen for Trop-2 expression in patients with pathological complete response (N=22) and residual disease (N=42) (median 100 vs 100 H-score, p=0.96). Higher Trop-2 expression was seen in lean compared to obese patients (100 vs 50, p=0.03). Conclusion In patients with TNBC treated with upfront surgery, higher Trop-2 expression was correlated with older age, more LVI and nodal involvement. There was overall no correlation between Trop-2 expression with sTILs, AR or outcome. Limited numbers of events warrant caution in interpretation.
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. Correlation of Trop-2 expression with clinicopathological characteristics and outcome in triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-16.