Evaluation of the predictive role of tumor immune infiltrate in patients with HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy without chemotherapy Journal Article

   

Authors:	De Angelis, C.; Nagi, C.; Hoyt, C. C.; Liu, L.; Roman, K.; Wang, C.; Zheng, Y.; Veeraraghavan, J.; Sethunath, V.; Nuciforo, P.; Wang, T.; Tsimelzon, A.; Mao, S.; Hilsenbeck, S. G.; Trivedi, M. V.; Cataldo, M. L.; Pavlick, A.; Wolff, A. C.; Weigelt, B.; Reis-Filho, J. S.; Prat, A.; Gutierrez, C.; Osborne, C. K.; Rimawi, M. F.; Schiff, R.
Article Title:	Evaluation of the predictive role of tumor immune infiltrate in patients with HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy without chemotherapy
Abstract:	Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2þ 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 1⁄4 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 ERþ 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 1⁄4 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 1⁄4 0.057). Unsupervised hierarchical clustering of the five immune markers identified two patient clusters with different responses to lapatinib plus trastuzumab treatment (pCR 1⁄4 7% vs. 50%, for cluster 1 vs. 2 respectively; P 1⁄4 0.01). In multivariable analysis, cluster 2, characterized by high CD4þ, CD8þ, CD20þ s-TILs, and high CD20þ intratumoral TILs, was independently associated with a higher pCR rate (P 1⁄4 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-CD20þ TILs. Conclusions: LPBC was marginally associated with higher pCR rate than non-LPBC in patients with lapatinib plus trastuzumab treated HER2þ 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.
Keywords:	adult; controlled study; human tissue; treatment response; middle aged; human cell; major clinical study; histopathology; polymerase chain reaction; cd8 antigen; transcription factor foxp3; tumor associated leukocyte; disease association; cohort analysis; tumor biopsy; immunofluorescence; tumor marker; loading drug dose; cd20 antigen; cellular immunity; cancer infiltration; staining; eosin; hematoxylin; letrozole; cd4 antigen; gonadorelin agonist; neoadjuvant chemotherapy; trastuzumab; stroma cell; lapatinib; predictive value; cd68 antigen; estrogen receptor positive breast cancer; human epidermal growth factor receptor 2 positive breast cancer; human; female; priority journal; article; multispectral imaging; progesterone receptor positive breast cancer
Journal Title:	Clinical Cancer Research
Volume:	26
Issue:	3
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2020-02-01
Start Page:	738
End Page:	745
Language:	English
DOI:	10.1158/1078-0432.Ccr-19-1402
PUBMED:	31653641
PROVIDER:	scopus
PMCID:	PMC7002194
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079022778&doi=10.1158%2f1078-0432.CCR-19-1402&partnerID=40&md5=f1efc6c74deedd3bce13491499e85f67
Notes:	Article -- Export Date: 2 March 2020 -- Source: Scopus

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