Correlation of TROP-2 expression with clinical–pathological characteristics and outcome in triple-negative breast cancer

Abstract

Limited data exist regarding the associations between TROP-2 protein expression, clinical–pathological characteristics, and outcome in triple-negative breast cancer (TNBC). TROP-2 expression was determined for patients diagnosed with TNBC between 2000 and 2017 by immunohistochemistry (IHC) (ab227689, Abcam) on whole slide tumor sections, and assessed as continuous and categorical variables (H-score high, 201–300, medium 100–200 and low < 100). We investigated the prognostic value of TROP-2 expression for relapse and survival, associations between TROP-2 expression and baseline patient and tumor characteristics, stromal tumor-infiltrating lymphocytes (sTILs), androgen receptor (AR), standardized mitotic index (SMI) and pathological complete response (pCR, in patients with neoadjuvant chemotherapy) were assessed. We included 685 patients with a median age at diagnosis of 54 years (range 22–90 years). After median follow-up of 9.6 years, 17.5% of patients experienced distant relapse. TROP-2 expression was high, medium and low in 97 (16.5%), 149 (25.3%) and 343 (58.2%) of patients, respectively. The presence of LVI, associated DCIS, nodal involvement, apocrine histology and AR expression were correlated with higher TROP-2 levels. There were no associations between TROP-2 expression and sTILs, time-to-event outcomes, or pCR rate after neoadjuvant chemotherapy. TROP-2 expression is not associated with sTILs level and has no prognostic value in our cohort of stage 1–3 TNBC. However, an association with histotype and AR expression was found, suggesting a histotype specific TROP-2 expression pattern with highest expression in apocrine subtype, warranting further research.

The Impact of Trophoblast Cell-Surface Antigen 2 Expression on the Survival of Patients with Gastrointestinal Tumors: A Systematic Review

“…Findings from Italiano et al were unanimous in advanced nonsmall-cell lung cancer (NSCLC), as shorter median overall survival for patients was demonstrated (12.6 vs. 16.3 months, p = 0.007) [26]. In early triple negative breast cancer, patients with high TROP-2 had higher rates of nodal involvement (53%) compared to patients with medium (23%) and low (21%) TROP-2 expression (p = 0.03) and more frequent lymphovascular invasion (65% of patients with high TROP-2 vs. 15-16% of patients with medium and low TROP-2 expression, p ≤ 0.001) [27]. Amborgi et al showed that TROP-2 is an unfavorable prognostic factor when localized in the membrane of breast cancer cells in terms of overall survival (HR = 1.63, p = 0.04), whereas a favorable effect was observed in intracellular expression (HR = 0.48, p = 0.003) [28].…”

Can ADCs broaden the treatment landscape of metastatic ER+/HER2− breast cancer resistant to CDK4/6 inhibition?

“…The targeted release of cytotoxic agents is expected to be less associated with side effects than the use of standard chemotherapy regimens. However, in the ASCENT trial, the use of SG was associated with more neutropenia (63 vs. 43%), anaemia (34 vs. 24%), diarrhea (59 vs. 12%), nausea (57 vs. 26%) and fatigue (45 vs. 30%) than classic regimens with chemotherapy ( 15 ). Most side effects were of low grade and did not lead to treatment discontinuation.…”

“…At present, SG is only FDA approved for use in patients with metastatic triple negative breast cancer ( 13 ). SG makes use of an antibody directed at binding TROP-2, an epithelial antigen expressed in multiple solid cancers ( 14 , 15 ). The TROP-2 antibody is linked to a topoisomerase-1 inhibitor payload with a high drug to antibody ratio (DAR; 7:1).…”

Trop-2 as an Actionable Biomarker in Breast Cancer

“…In breast cancer, Trop-2 has been tested using an Anti-Trop2 B9 sc-376746 antibody (Santa Cruz), scoring the staining intensity from 0 to 3 [ 19 ]. Another assay previously used in TNBC translational research is the Ab227689 (Abcam) on the Bond Automatic IHC Stainer (Leica Biosystems) [ 20 ]. In this study, the authors found an association between Trop-2 and apocrine phenotype [ 20 ].…”

“…Another assay previously used in TNBC translational research is the Ab227689 (Abcam) on the Bond Automatic IHC Stainer (Leica Biosystems) [ 20 ]. In this study, the authors found an association between Trop-2 and apocrine phenotype [ 20 ]. A summary of clinical trials enrolling patients with breast cancer in which Trop-2 status is being tested, along with the specific methodology, is provided in Table 1 .…”