165P - Correlation between trophoblast cell-surface antigen-2 (Trop-2) expression and pathological complete response (pCR) in HER2-positive early breast cancer (EBC): A sub analysis of PHERGain trial

Background

Trop-2 is a transmembrane calcium signal transducer widely expressed in multiple tumor types on the membrane surface of epithelial cells. Antibody-drug conjugates targeting Trop-2 are currently being developed for the treatment of breast cancer. However, there is little data regarding the therapeutic implications of Trop-2 expression in HER2-positive breast cancer.

Methods

Trop-2 expression, as determined by immunohistochemistry (IHC) and its relationship with clinicopathologic features and pCR, was retrospectively analyzed in patients (pts) with HER2-positive EBC treated with upfront neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab in the PHERGain study (Pérez-García et al, Lancet Oncol 2021). Trop-2 expression was classified into low, medium, and high groups according to a histochemical score (H-score) based on staining intensity and percentage of stained cells.

Results

A total of 41 pts were included. Of these, 31.7% (13/41) had node-positive disease and 63.4% (26/41) were estrogen receptor-positive. 68.3% (28/41) of the tumors showed Trop-2 expression (low [29.3%]; medium [17.1%]; and high [21.9%]). No relationship was found between Trop-2 expression and different clinicopathologic features, but there was a trend toward higher progesterone receptor negativity among Trop-2-expressing tumors (p = 0.098). pCR was achieved in 63.4% (26/41) of the pts. According to Trop-2 expression, pCR rates were 50.0% (14/28) and 92.3% (12/13) in pts with and without Trop-2 expression, respectively (p=0.015).

Conclusions

Trop-2 expression by IHC was identified in approximately two thirds of HER2-positive EBC pts. Trop-2 appears to be a potential mechanism of resistance in this patient population and may become a strategic target for future combinations.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

MEDSIR - Medica Scientia Innovation Research.

Funding

Fundación Contigo.

Disclosure

M. Gion Cortes: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer. J.M. Pérez-García: Financial Interests, Personal, Advisory Role: Lilly, Roche, Eisai, Daiichi Sankyo, AstraZeneca, Seattle Genetics, Gilead; Financial Interests, Personal, Other, travel expenses: Roche; Financial Interests, Personal, Full or part-time Employment: MEDSIR. J.A. Guerrero, L. López-Montero, M. Mancino, J. Rodríguez Morató: Financial Interests, Personal, Full or part-time Employment: MEDSIR. A. Llombart Cussac: Financial Interests, Institutional, Research Funding: Roche, Agendia, Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Gilead, Daiichi Sankyo; Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, Roche, Pfizer, Novartis; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel support: Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Stocks or ownership: MEDSIR, Initia-Research. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp & Dohme, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. All other authors have declared no conflicts of interest.