Tumor immune microenvironment (TiME) changes by multiplex IF staining in a pilot study of neoadjuvant talazoparib for early-stage breast cancer patients with a BRCA mutation.

Evthokia Hobbs University of Texas MD Anderson Cancer Center, Houston, TX info_outline Evthokia Hobbs, Fei Yang, Tapsi Kumar, Alejandro Contreras, Edwin Roger Parra Cuentas, Haven Garber, Marion Scoggins, Beatriz E Adrada, Gary J Whitman, Banu Arun, Elizabeth A. Mittendorf, Jennifer Keating Litton

Authors Evthokia Hobbs University of Texas MD Anderson Cancer Center, Houston, TX info_outline Evthokia Hobbs, Fei Yang, Tapsi Kumar, Alejandro Contreras, Edwin Roger Parra Cuentas, Haven Garber, Marion Scoggins, Beatriz E Adrada, Gary J Whitman, Banu Arun, Elizabeth A. Mittendorf, Jennifer Keating Litton Organizations University of Texas MD Anderson Cancer Center, Houston, TX, The University of Texas MD Anderson Cancer Center, Houston, TX, MDACC, Houston, TX, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA Abstract Disclosures Research Funding Other Foundation Other Foundation, Pharmaceutical/Biotech Company Background: We previously reported a median tumor volume loss of 88% (range 30-98%) in 13 patients with early stage BRCA1/2 mutant breast cancer treated on a neoadjuvant trial of the PARP inhibitor talazoparib. The effects of PARP inhibition on immune aspects of the TiME in early-stage breast cancer has not been well described. The goal of this study was to evaluate the TiME in pre and post-treatment core biopsies from enrolled patients. Methods: Eleven paired core biopsies were available for examination. Tumor infiltrating lymphocytes (TILs) were quantified by H&E stained slides by a central pathologist. Specimens were assessed by multiplex immunofluorescence (mIF) using a panel of 6 biomarkers (PD-1, PD-L1, CD3, CD8, CD68 and CK) with the Opal 7-color Kit in LEICA BOND auto stainer, Vectra automated quantitative pathology imaging system and inForm software (PerkinElmer). Results: In the analyzed core biopsies, there was an increase in TILs evaluated by H&E in post-treatment compared to baseline (mean 36 vs 11%). By mIF there was an increase in CD3+ T cell and CD3+CD8+ cytotoxic T cell density in post-treatment samples compared to baseline, summarized in table. PD-L1 expression in tumor cells was rare in the cohort. There was no difference in CD3+PD-1+ or CD3+CD8+ PD-1+ lymphocytes in pre and post-treatment specimens. There was also no differences in macrophages (CD68+). Evaluation of immune phenotype and imaging response will be presented in the final analysis. Conclusions: This is the first study phenotyping the immune response to neoadjuvant talazoparib in BRCA-mutant breast cancer patients. In this small cohort, intratumoral and stromal CD3+ T cells and CD3+CD8+ cytotoxic T cells increased after two months of talazoparib. Clinical trial information: NCT02282345 Pre-treatment (mean density/mm 2 ) Post-treatment (mean density/mm 2 ) Tumor CD3+ 164.22 668.61 Tumor CD3+CD8+ 84.65 341.48 Stroma CD3+ 743.78 1070.88 Stroma CD3+CD8+ 163.82 429.92 Tumor & stroma CD3+ 348.30 975.80 Tumor & stroma CD3+CD8+ 109.27 395.08