Abstract P1-08-25: Evaluating an ex vivo organ culture system for predicting response to neoadjuvant chemotherapy in breast cancer patients
Authors: Gal-Yam Einav Nili , Sklair-Levi Miri , Vachnish Yaeli , Balint-Lahat Nora , Morzaev-Sulzbach Dana , Bakalenik-Gavry Michal , Fearmann Renata , Halshtok Osnat , Shalmon Anat , Gotlieb Michael , Yagil Yael , Levanon Keren , Bernstein-Molho Rinat , Itay Amit , Shapira-Rotenberg Tali , Globus Opher , Barshack Iris , Salpeter Seth , Bar Vered , Aharon Sara , Turovsky Lubov , Zundelevich Adi , Mallel Giuseppe , Shahar Hamutal , Shapira Hagit , Dadiani Maya 
Published: March 2022

Abstract
Background. Neoadjuvant chemotherapy (NACT) is increasingly administered for high-risk breast cancer patients. Yet, oncologists lack an effective method for assessing response to treatment beyond clinicpathological features. Organ tissue slices freshly obtained from the tumor and incubated in appropriate media, recapitulate the tumor’s heterogeneity and may provide a superior ex-vivo model for predicting response/resistance to treatment. While these models were tested in metastatic tumors, no studies up to date have been reported in early breast cancer or for NACT. These tests have short turnaround time (7-9 days), critical for the neoadjuvant setting. Here we aimed to prove the feasibility of performing cResponse assay, an ex vivo organ culture (EVOC), on freshly derived pre-treatment core needle biopsies and to evaluate it as a tool for predicting response to NACT in breast cancer. Methods. Pre-treatment tumor biopsies were obtained from breast cancer patients about to undergo NACT at the time of routine tumor clip marking. The fresh samples were immediately placed in cold medium, sliced into 250um sections and cultured in multiwell plates. The samples were treated with the clinically administered therapies or a vehicle control. The various therapies included Doxorubicin (A), Paclitaxel (T), Cytoxan (C) and in TN cases, Carboplatin (Cr), as single agents or in combination in clinically administered ratios. After 4 days of treatment, tumor slices were fixed and stained to allow morphological analysis. A trained pathologist examined the stained slides and scored the viable cancer cells. A response-score was generated and compared to the pathological result (pCR status and RCB class) of the patient at surgery.Results. Tumor samples from 15 breast cancer patients were examined. The cohort median age was 42 (32—82), LN involvement 9/15, subtypes status: 9 HR+, 2 TNBC, 3 HR+HER2+ and 1 HR-HER2+. Nine samples were either excluded due to insufficient viable cancer cells or necrosis and one sample failed technically. Five samples (2 TNBC, 2 HR+ and 1 HR+HER2+) were adequate for analysis and obtained cResponse scores. The HR+HER2+ case received a different protocol than actually tested, thus was not compared. For the four successful cases, the cResponse score was highly concordant with response to therapy (Table I). For the two TNBC samples, a maximal cResponse score (100) was demonstrated for AC-T or AC-TC combination and both patients achieved complete response (pCR, RCB-0) at surgery. Notably, in one patient, the assay predicted maximal response for the TC combination, suggesting that this protocol could be sufficient. For the HR+ patients, one patient demonstrated a strong cResponse to AC-T (85) and achieved near complete response (RCB-I), while the second patient demonstrated a moderate cResponse score (70) and achieved partial pathological response (RCB-II). Conclusions. We provide initial evidence for the feasibility and validity of an EVOC platform to predict response to NACT in breast cancer. Further optimizations are needed to increase the assay’s success rates. We expect the results to set the ground for a clinical trial, examining the utility of the cResponse test as predictive biomarker in determining NACT. This technology may provide a tool for the oncologist to select the most efficient therapies, maximizing pCR rates and minimizing toxicity from ineffective drugs, eventually improving prognosis of breast cancer patients.
Table IPatientSubtypeBest cResponse scoreBest treatmentsPathological ResponseRCB classNAT-2HR+70AC-T/AC/CPartialRCB-IINAT-3TN100AC-TCr/TCrpCRRCB-0NAT-12TN100A/AC-TpCRRCB-0NAT-16HR+85AC-TPartialRCB-I
Citation Format: Einav Nili Gal-Yam, Miri Sklair-Levi, Yaeli Vachnish, Nora Balint-Lahat, Dana Morzaev-Sulzbach, Michal Bakalenik-Gavry, Renata Fearmann, Osnat Halshtok, Anat Shalmon, Michael Gotlieb, Yael Yagil, Keren Levanon, Rinat Bernstein-Molho, Amit Itay, Tali Shapira-Rotenberg, Opher Globus, Iris Barshack, Seth Salpeter, Vered Bar, Sara Aharon, Lubov Turovsky, Adi Zundelevich, Giuseppe Mallel, Hamutal Shahar, Hagit Shapira, Maya Dadiani. Evaluating an ex vivo organ culture system for predicting response to neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-25.