Comparative expression of trophoblast cell-surface antigen 2 (TROP2) in the different molecular subtypes of invasive breast carcinoma: An immunohistochemical study of 94 therapy-naive primary breast tumors

Background: Sacituzumab govitecan, targeting trophoblast cell-surface antigen 2 (TROP2), is approved for the treatment of triple-negative and hormone receptor-positive/HER2-negative breast cancers. However, detailed studies comparing TROP2 protein expression in the different molecular subtypes of breast cancer are limited, and definitive evidence supporting the use of TROP2 as a biomarker for predicting response to this agent in patients with breast cancer is currently lacking.Objective: To compare the expression of TROP2 in the different molecular subtypes of breast cancer. Methods: Immunohistochemical staining for TROP2 was performed on 94 therapy-naive primary invasive breast carcinomas, including 25 luminal A-like, 25 luminal B-like, 19 HER2-like, and 25 triple-negative tumors.Results: Intermediate to high levels of TROP2 expression were observed in the majority of carcinomas of each molecular subtype, with a wide range of expression in each subtype. Occasional tumors with low or absent TROP2 expression were encountered, including two metaplastic carcinomas which were completely negative for TROP2.Conclusions: Our observations support the continued investigation of the efficacy of sacituzumab govitecan in all molecular subtypes of breast carcinoma. Furthermore, the observed wide range of expression of TROP2 suggests that TROP2 may have potential utility as a biomarker for predicting responsiveness to sacituzumab govitecan. If this proves to be the case, then immunohistochemical staining for TROP2 would be critical for identifying those patients whose tumors are completely negative for TROP2, since these patients may be least likely or unlikely to respond to this agent, and alternative therapies may be more appropriate in such instances.

Automated summary

This study compared the expression of TROP2 in different molecular subtypes of breast cancer and found that a majority of carcinomas in each subtype showed intermediate to high levels of TROP2 expression with a wide range of expression. These observations support further investigation of the efficacy of sacituzumab govitecan in all molecular subtypes of breast carcinoma. The wide range of TROP2 expression suggests its potential utility as a biomarker for predicting responsiveness to sacituzumab govitecan. Immunohistochemical staining for TROP2 is critical for identifying patients who are completely negative for TROP2 and may be least likely or unlikely to respond to this agent.