Résumé
Background: Since the development of anti Trop2 antibody-drug conjugates (ADC), Trop2 has been validated as a major therapeutic target for antibody-drug conjugates in metastatic triple-negative breast cancer (TNBC). However, very few data have been reported regarding the prognostic implication, or clinicopathological variables, associated with Trop2 expression levels in early TNBC. Our aim was to evaluate Trop2 expression and its prognostic value in a retrospective series of patients with non-metastatic TNBC and a long follow-up, characterized for Basal-like (BL) or molecular apocrine-like (MA) IHC profiles as well as TILs infiltrate, PDL1 expression and PIK3CA/PTEN mutations. Patients and methods: The analysis was performed in a series of 228 patients with non-metastatic TNBC treated in our center between 2002 and 2012 arrayed on 6 TMA. BL and MA profiles were defined as IHC CK5/6 and/or EGFR expression, and Androgen-receptor and FOXA1 IHC expression, respectively. Trop2 expression levels were tested for their association with baseline clinicopathological variables, and for Relapse-Free Survival (RFS) and Overall survival (OS). Trop2 IHC level of expression was evaluated using the ENZ-ABS380 mouse monoclonal antibody and the methodology described by Bardia et al. (Annals of Oncology, 2021) to quantify the membrane signal. First, we established a score grid, according to staining intensity (no labeling: 0; weak labeling: 1; moderate labeling: 2; strong labeling: 3). Then, for each sampled core, the percentage of labeled invasive tumor cells in each intensity was reported. The overall membrane expression was then calculated using the H-Score method (3 x % of cells with labeling intensity 3 + 2 x % of cells with intensity 2 + 1 x % of cells with intensity 1). The scores obtained ranged from 0 to 300. Results: Median age was 58.2 years (range 28.5-89.1). 43.9% of tumors were classified pT1 and 63.5% pN0. 83.8% of patients had ductal carcinomas. Histological grade 1-2 represented 22.7% of all tumors. A BL phenotype was observed in 68.1% of cases, and an MA profile in 39.4% of the cases. Adjuvant chemotherapy (ACT) was delivered in 74% of patients. We observed low Trop2 expression (H-Score < 100) in 12.3% of the cases (28/228 samples), moderate Trop2 expression (H-Score 100-200) in 28.9% of the cases (66/228 samples), and strong Trop2 expression (H-Score >200) in 58.8% of the cases (134/228 samples). We only identified 3 tumors without any Trop2 expression. Regarding baseline clinicopathological correlations, Trop2 levels were only found significantly associated with pT stage, pT1 tumors displaying more frequently high Trop2 scores compared to tumors >= pT2 (p=0.002). No significant correlation was found between Trop2 expression levels and HER2 levels (0 vs. 1+/2+), BL or MA status. With a median follow-up of 9.7 years, Trop2 levels were not associated with RFS nor OS in univariate analysis. In multivariate analysis, poor RFS was associated with classical variables in the early TNBC setting: tumors >=T2 stage (Hazard Ratio (HR) 2.13, p=0.02), N+ status (HR 3.51, p< 0.001), while high (>5%) TILs infiltration levels (HR 0.54, p=0.03) and adjuvant chemotherapy use (HR 0.49, p=0.007) were associated with improved RFS. Conclusions: Trop2 is expressed in nearly all early TNBC cases, and Trop2 levels of expression, while associated with T stage, did not impact survival in this population. These results are consistent with the ones reported in the metastatic setting in the ASCENT trial. Trop2 level of expression appearing homogeneous distributed in all the clinicopathological subtypes of TNBC, advocating for the evaluation of combined treatments with anti-Trop2 ADCs and dedicated targeted therapies in specific TNBC subgroups.
Citation Format: William Jacot, Marie-Christine Chateau, Simon Thezenas, Séverine Guiu, Nelly Firmin, Florence Boissière-Michot. Prognostic value of Trop2 expression levels in non-metastatic triple-negative breast cancer and correlation with other biomarkers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-17.