Dataset Information

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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Publications

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]

PMID: 31653641

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Project description:BACKGROUND:We previously reported that in patients with HER2-positive (HER2+) locally advanced breast cancer treated with neoadjuvant trastuzumab-containing regimens, high HER2 to centromere enumerator probe 17 ratio on fluorescence in situ hybridization (HER2 FISH ratio) was an independent predictor of high pathologic complete response (pCR) rate, which translated into improved recurrence-free survival (RFS). We sought to determine whether high HER2 FISH ratio is a predictor of pCR and prognosis in patients with HER2+ nonmetastatic inflammatory breast cancer (IBC) and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab. MATERIALS AND METHODS:This study included all patients with histologically proven stage III, HER2+ primary IBC, and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab and definitive surgery during 1999-2012. Univariate and multivariate logistic regression models were applied to assess the effect of covariates on pCR. Kaplan-Meier estimates with log-rank test were employed for survival analysis. Univariate and multivariate Cox proportional hazards models were used to assess the effect of covariates on RFS and overall survival (OS). RESULTS:The study included 555 patients with stage III, HER+ breast cancer, 181 patients with IBC, and 374 with non-IBC. In the IBC cohort, HER2 FISH ratio was not significantly associated with pCR, RFS, or OS. In the non-IBC cohort, higher HER2 FISH ratio was significantly associated with higher pCR rate and longer OS. CONCLUSION:HER2 FISH ratio showed prognostic value among patients with HER2+ non-IBC but not HER2+ IBC treated with neoadjuvant chemotherapy. This disparity may be due to the underlying aggressive nature of IBC. IMPLICATIONS FOR PRACTICE:The findings of this study indicate that the HER2 to fluorescence in situ hybridization ratio as a continuous variable has promise as a predictor of pathologic complete response to neoadjuvant chemotherapy in patients with HER2-positive (HER2+) noninflammatory breast cancer (non-IBC) regardless of the results on HER2 immunohistochemical testing. In the future, some patients with HER2+ non-IBC and a high HER2 FISH ratio might even be offered personalized treatment options, such as nonsurgical treatment.

Dataset Information

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

Purpose

Results

Conclusions

Publications

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

Similar Datasets

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