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ABSTRACT: 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.
SUBMITTER: De Angelis C
PROVIDER: S-EPMC7002194 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
De Angelis Carmine C Nagi Chandandeep C Hoyt Cliff C CC Liu Linying L Roman Kristin K Wang Chichung C Zheng Yi Y Veeraraghavan Jamunarani J Sethunath Vidyalakshmi V Nuciforo Paolo P Wang Tao T Tsimelzon Anna A Mao Sufeng S Hilsenbeck Susan G SG Trivedi Meghana V MV Cataldo Maria Letizia ML Pavlick Anne A Wolff Antonio C AC Weigelt Britta B Reis-Filho Jorge S JS Prat Aleix A Gutierrez Carolina C Osborne Charles Kent CK Rimawi Mothaffar F MF Schiff Rachel R
Clinical cancer research : an official journal of the American Association for Cancer Research 20191025 3
<h4>Purpose</h4>Tumor-infiltrating lymphocytes (TIL) are associated with benefit to trastuzumab and chemotherapy in patients with early-stage HER2<sup>+</sup> breast cancer. The predictive value of TILs, TIL subsets, and other immune cells in patients receiving chemotherapy-sparing lapatinib plus trastuzumab treatment is unclear.<b>Experimental Design:</b> Hematoxylin and eosin-stained slides (<i>n</i> = 59) were used to score stromal (s-)TILs from pretreatment biopsies of patients enrolled in t ...[more]