Molecular characterization of trophoblast cell surface antigen 2 (Trop-2) positive triple negative breast cancer (TNBC).

e14651 Background: Trop-2 is a glycoprotein found in various carcinomas, known to play a role in tumor development and progression. A humanized antibody drug conjugate (ADC) targeting Trop-2 for delivery of the topoisomerase-I (TOPO1) inhibitor SN-38 (payload) is currently in clinical development for TNBC. Clinical response in a previously reported phase I/II study was associated with Trop-2 immunohistochemistry (IHC) staining intensity (Bardia A et al. J Clin Oncol 2017). Herein we investigated the prevalence of Trop-2 expression in an unselected cohort of TNBC tumors, and the association with other markers of interest that could suggest novel drug combinations. Methods: A cohort of 68 TNBC specimens with available archival tumor submitted to Caris Life Sciences were tested via protein expression (IHC) for Trop-2 with dichotomous categorization for results. Positivity required at least 10% of tumor cells to be stained, with an intensity of 1+ (weak), 2+ (moderate) and 3+ (strong), with same cutoff used in ongoing clinical trials of Trop-2 ADC. Comprehensive molecular profiles were performed using 592-gene next generation sequencing (average read depth 500X). Chi-square tests were used for statistics. Results: The median age in this cohort was 54 (range: 28-90). 38 (56%) tumors were positive for Trop-2. There was no difference in age distribution between Trop-2 positive and negative tumors. Trop-2 expression was present in 48.6% (17/35) and 63.6% (21/33) of primary and metastatic sites, respectively. TOPO1 by IHC was negative in 11 (29%) of Trop-2 positive tumors. Trop-2 expression was inversely associated with PIK3CA and RB1 mutations (p = 0.012 and 0.011, respectively). There was no difference in PDL1 expression by IHC, tumor mutational burden (TMB), BRCA1/2 or other homologous recombination deficiency gene mutations between Trop-2 positive and negative tumors. Conclusions: In a cohort that used the same cutoffs in ongoing trials with Trop-2 ADC, we found a lower prevalence of Trop-2 positivity in TNBC than what has been previously reported. One third of Trop-2 positive tumors were TOPO1 negative which may have treatment implications given the pharmacology of ADC currently in development.