Breast Cancer

PV QA 4 - Poster Viewing Q&A 4

TU_1_3328 - Characterization of the Tumor Microenvironment (TME) with Quantitative Multiplex Immunofluorescence (qMIF) in a cohort of Neoadjuvant Breast Cancer (BC) patients: a pilot analysis

Tuesday, October 23
2:45 PM - 4:15 PM
Location: Innovation Hub, Exhibit Hall 3

Characterization of the Tumor Microenvironment (TME) with Quantitative Multiplex Immunofluorescence (qMIF) in a cohort of Neoadjuvant Breast Cancer (BC) patients: a pilot analysis
C. Chin1,2, D. Marks3, T. D. Hart3, Y. Saenger3, H. Hibshoosh4, K. M. Kalinsky3, and E. P. Connolly2,5; 1New York Presbyterian Columbia Campus, New York, NY, 2Department of Radiation Oncology, Columbia University Medical Center, New York, NY, 3Department of Medical Oncology, Columbia University Medical Center, New York, NY, 4Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 5Dept of Radiation Oncology, Columbia University Medical Center, New York, NY

Purpose/Objective(s): Tumor-infiltrating lymphocytes (TILs) have been shown to be predictive of chemosensitivity and prognostic of survival in BC. In the neoadjuvant setting lymphocyte predominant breast cancers, defined by the presence of >40% TIL density, have higher rates of pathological complete response (pCR) after neoadjuvant chemotherapy (NCT) as well as improved disease-free and overall survival. This observation, however, has not led to sufficiently precise biomarkers that accurately identify patients at high-risk of relapse. Recent studies have suggested that spatial localization of immune cells within the TME can serve as a surrogate for functional activity and may add prognostic and predictive power to analysis of the TME. We aim to characterize the TME with qMIF in a cohort of locally advanced BC patients treated with doxorubicin and/or taxane-based NCT.

Materials/Methods: We obtained tumor tissue of 160 BC patients for whom pre-NCT biopsy and post-NCT surgical pathology was available for review. 12 patients within this cohort also had tissue available from the time of relapse. qMIF was performed to allow for simultaneous visualization of immune biomarkers (DAPI, CD3, CD8, CD68, HLA-DR, PDL-1, pancytokeratin) on full section (4uM) tissue slides. Images were taken using Vectra® (PerkinElmer, Waltham, MA) and analyzed in both HALO™ (Indica Labs, Corrales, NM) and inForm® Cell Analysis™ (PerkinElmer) software to perform cell segmentation and phenotyping. Here we present preliminary results from a pilot cohort of 6 patients with known relapse.

Results: Of the 160 patients included in our study, 37 (23%) achieved a pCR. At a median follow-up of 51 months, 14 locoregional recurrences and 34 distant relapses occurred. In our pilot subgroup of 6 patients, median time to relapse was 20.5 months (range 16-34 months). On qMIF analysis, all patients were TIL-poor on pre-NCT biopsy (mean 2%, range: 0-7%) with no observed pCRs. We observed a trend of increased macrophage (CD68+) density following NCT, a profile that has been associated with a worse disease-free survival, and a return of macrophage and cytotoxic T-cells (CD3CD8+) to pre-NCT levels at the time of local and/or distant relapse in the majority of patients.

Conclusion: This small pilot represents the preliminary analysis of a larger study that aims to identify precise biomarkers predictive of pCR and survival in both pre- and post-NCT tumor specimens. The results of our larger cohort will be presented at the upcoming meeting. Insight into the specific immune subsets and interactions that contribute to improved NCT response and relapse-free survival will help to identify biomarkers that may guide management of high-risk BC patients who may benefit from clinical trials in the neoadjuvant or adjuvant setting.

Author Disclosure: C. Chin: None. D. Marks: None. T.D. Hart: None. Y. Saenger: None. H. Hibshoosh: None. K.M. Kalinsky: None. E.P. Connolly: Employee; Celgene. Research Grant; Eisai, Merck. Advisory Board; Eisai.

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