Abstract P5-01-09: Prospective genomic and PD-L1 profiling of patients with residual triple negative breast cancer after neoadjuvant chemotherapy
Authors: Irie Hanna Yoko , Schmidt Paul , Port Elisa , Berger Natalie , Klein Paula , Kinoshita Yayoi , Soto Alan , Pisapati Kereeti , Couri Ronald , Kolodka Olivia , Arib Hanane , Sebra Robert , Donovan Michael J 
Published: March 2020

Abstract
Background/Rationale: Sensitivity to chemotherapy consistently remains a strong predictor of long term outcomes and survival for patients diagnosed with triple negative breast cancer (TNBC). Patients who do not achieve a complete pathological response to pre-operative, neoadjuvant chemotherapy are at increased risk for metastatic recurrence. Clinical trials with targeted therapies and immunotherapies aim to reduce this risk of recurrence for this patient population. As part of our ongoing prospective study of patients with TNBC that involves serial blood collections and tissue collections (pre-treatment biopsy and post-neoadjuvant surgical specimen) from the time of initial diagnosis, we are particularly focused on those patients with residual disease following neoadjuvant treatment. Comprehensive tissue and cell-free DNA (cfDNA)/circulating tumor cell (CTC) profiling of these patients could lead to insights into mechanisms of chemotherapy resistance and new treatment strategies to prevent recurrences. In addition to genomic profiling, we have analyzed PD-L1 expression on tissue and CTC’s which may contribute to improve targeted utilization of immunotherapies for patients with early stage, high-risk TNBC. Methods: Patients diagnosed with TNBC (stage 1-3) are consented for this prospective study. Serial collections of blood are obtained at time of initial diagnosis, following neoadjuvant chemotherapy or upfront surgery and at 6 month intervals following completion of all active therapy. cfDNA/CTC are isolated using Cynvenio’s Liquid Biopsy platform and sequenced on a rolling basis with Oncomine V3 panel. Tissue from initial biopsy and surgical resection are also collected and sequenced. PD-L1 staining of breast tumor tissue and CTC is performed using antibody SP-142 and atezolizumab, respectively. Clinical outcomes (response to chemotherapy and recurrence data) are also recorded. Results: 30 patients are currently being followed. Of these 24 patients were treated with neoadjuvant chemotherapy and 10/24 (42%) had a pathological complete response (pCR). For the patients treated with neoadjuvant chemotherapy whose pre-treatment samples have been sequenced, 3/6 (50%) of patients who did not achieve a pCR had pre-treatment detectable mutations in cfDNA/CTC in contrast to 3/9 (33%) patients who achieved a pCR. Furthermore, all 6 patients who had residual disease had at least one blood collection with detectable cfDNA/CTC mutations following completion of all active breast cancer therapy. For the five patients with post-neoadjuvant residual disease whose surgical specimens have been stained for PD-L1 expression, 4/5 (80%) are PD-L1 positive (&gt;1%) either in the tumor or infiltrating leukocyte population. PD-L1 positive circulating CTC’s were also detected in 1 of these patients with PD-L1 positive residual disease thus far. Conclusions: Prospective serial analysis of cfDNA/CTC may identify patients who are at higher risk for incomplete response to neoadjuvant therapy or metastatic recurrence. PD-L1 staining of post-neoadjuvant residual cancer and/or CTC’s may help identify high risk patients most likely to benefit from adjuvant immunotherapy.
Citation Format: Hanna Yoko Irie, Paul Schmidt, Elisa Port, Natalie Berger, Paula Klein, Yayoi Kinoshita, Alan Soto, Kereeti Pisapati, Ronald Couri, Olivia Kolodka, Hanane Arib, Robert Sebra, Michael J Donovan. Prospective genomic and PD-L1 profiling of patients with residual triple negative breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-09.