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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 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

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

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]

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