Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy.

Autor:	De Angelis C; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Naples, Italy., Nagi C; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas., Hoyt CC; Akoya Biosciences, Hopkinton, Massachusetts., Liu L; Akoya Biosciences, Hopkinton, Massachusetts., Roman K; Akoya Biosciences, Hopkinton, Massachusetts., Wang C; Akoya Biosciences, Hopkinton, Massachusetts., Zheng Y; Akoya Biosciences, Hopkinton, Massachusetts., Veeraraghavan J; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Sethunath V; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Nuciforo P; Breast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Wang T; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas., Tsimelzon A; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Mao S; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Hilsenbeck SG; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Trivedi MV; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas., Cataldo ML; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas.; Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Naples, Italy., Pavlick A; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas., Wolff AC; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland., Weigelt B; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Reis-Filho JS; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Prat A; Department of Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain.; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain., Gutierrez C; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Osborne CK; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Rimawi MF; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Medicine, Baylor College of Medicine, Houston, Texas., Schiff R; Lester and Sue Smith Breast Center and Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas. rschiff@bcm.edu.; Department of Medicine, Baylor College of Medicine, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Feb 01; Vol. 26 (3), pp. 738-745. Date of Electronic Publication: 2019 Oct 25.
DOI:	10.1158/1078-0432.CCR-19-1402
Abstrakt:	Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2 + breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear. Experimental Design: Hematoxylin and eosin-stained slides ( n = 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in the neoadjuvant TBCRC006 trial of 12-week lapatinib plus trastuzumab therapy (plus endocrine therapy for ER + tumors). A 60% threshold was used to define lymphocyte-predominant breast cancer (LPBC). Multiplexed immunofluorescence (m-IF) staining (CD4, CD8, CD20, CD68, and FoxP3) and multispectral imaging were performed to characterize immune infiltrates in single formalin-fixed paraffin-embedded slides ( n = 33). Results: The pathologic complete response (pCR) rate was numerically higher in patients with LPBC compared with patients with non-LPBC (50% vs. 19%, P = 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR = 7% vs. 50%, for cluster 1 vs. 2 respectively; P = 0.01). In multivariable analysis, cluster 2, characterized by high CD4 + , CD8 + , CD20 + s-TILs, and high CD20 + intratumoral TILs, was independently associated with a higher pCR rate ( P = 0.03). Analysis of single immune subpopulations revealed a significant association of pCR with higher baseline infiltration by s-CD4, intratumoral (i-) CD4, and i-CD20 + TILs. Conclusions: LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2 + breast cancer. Quantitative assessment of the immune infiltrate by m-IF is feasible and may help correlate individual immune cell subpopulations and immune cell profiles with treatment response. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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