Dataset Information

Clinical characteristics, tumor-infiltrating lymphocytes, and prognosis in HER2-low breast cancer: A comparison study with HER2-zero and HER2-positive disease.

ABSTRACT:

Introduction

HER2-low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor-infiltrating lymphocytes (sTILs) in this population.

Methods

Consecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2-low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) negative. sTILs were scored following the international guidelines. Clinicopathologic features and survival were compared according to HER2 and sTILs category.

Results

A total of 973 breast cancer patients were enrolled, including 615 (63.2%) HER2-low patients. HER2-low patients shared more similarity with HER2-0 cases in clinicopathological features. sTILs in HER2-Low patients was comparable to HER2-0 patients (p = 0.064), both significantly lower than HER2-positive ones (p < 0.001). Meanwhile, tumors with sTILs ≥50% accounted for the least proportion of HER2-low cases (p < 0.001). HER2 status had no significant influence on recurrence-free survival (RFS, p = 0.901) in the whole population. However, in the estrogen receptor (ER)-negative subgroup, HER2-low was related to worse RFS (p = 0.009) and OS (p = 0.001) compared with HER2-positive ones. sTILs increment was an independent favorable prognostic factor in the whole (OS, p = 0.003; RFS, p = 0.005) and HER2-low population (OS, p = 0.007; RFS, p = 0.009) after adjusted to clinicopathological parameters.

Conclusions

HER2-low patients shared similar clinicopathological features with HER2-0 rather than HER2-positive cases and had relatively low sTILs. ER-negative/HER2-low patients had significantly inferior survival. sTILs increment was independently associated with favorable survival in the HER2-low group, suggesting a potential benefit from a novel treatment strategy.

SUBMITTER: Lu Y

PROVIDER: S-EPMC10469737 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical characteristics, tumor-infiltrating lymphocytes, and prognosis in HER2-low breast cancer: A comparison study with HER2-zero and HER2-positive disease.

Lu Yujie Y Tong Yiwei Y Fei Xiaochun X Chen Xiaosong X Shen Kunwei K

Cancer medicine 20230627 15

<h4>Introduction</h4>HER2-low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor-infiltrating lymphocytes (sTILs) in this population.<h4>Methods</h4>Consecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2-low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) neg ...[more]

PMID: 37366301

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Project description:PurposeIt has been reported that breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2) might be a distinct subtype of BC. However, the prognostic effect of low HER2 expression on BC patients remains controversial. We aim to conduct this single-institution retrospective analysis to assess HER2-low-positive BC outcomes in Chinese women and the prognostic role of TILs in HER2-low-positive early-stage BC.MethodWe retrospectively enrolled 1,763 BC patients treated in a single institution from 2017 to 2018. TILs are regarded as continuous variables and are divided into low TILs (≤10%) and high TILs (>10%) for statistical analysis. Univariate and multivariable Cox proportional hazards regression models were used to test the associations between TILs and disease-free survival (DFS) with adjustment for clinicopathologic characteristics.ResultHigh TIL levels (>10%) were associated with tumor size (>2 cm, p = 0.042), age at diagnosis (p = 0.005), Ki-67 index (>25%; p <0.001), HR (hormone receptor) status (positive, p <0.001), advanced pathological stage (p = 0.043), subtype (p <0.001), and HER2 status (p <0.001). The Kaplan-Meier analysis indicated that no significant difference in DFS (p = 0.83) could be found between HER2-positive, HER2-low-positive, and HER2-0 BC. The DFS of HER2-low-positive BC and HER2-nonamplified BC with high levels of TILs was statistically better than that of patients with low levels of TILs (p = 0.015; p = 0.047). In HER2-low-positive BC patients with high TIL levels (>10%), DFS was significantly improved in both the univariate (HR = 0.44, 95% CI 0.22-0.87, P = 0.018) and multivariate (HR = 0.47, 95% CI 0.23-0.95, P = 0.035) Cox models. For further subgroup analysis, HR (+)/HER2-low-positive BC with high TIL (>10%) levels was associated with improved DFS in both the univariate (HR = 0.41, 95% CI 0.19-0.90, P = 0.025) and multivariate (HR = 0.42, 95% CI 0.19-0.93, P = 0.032) Cox models. The HR (-)/HER2-0 BC with high TIL (>10%) level was not statistically significant in the univariate Cox model, but it was statistically significant in the multivariate (HR = 0.16, 95% CI 0.28-0.96, P = 0.045) Cox model.ConclusionAmong early-stage BC, no significant survival difference could be found between the HER2-positive, HER2-low-positive, and HER2-0 cohorts. High levels of TILs were significantly associated with improved DFS in HER2-low-positive patients, especially in the HR (+)/HER2-low-positive subtype.

Project description:BackgroundThe influence of the tumor microenvironment and tumor-stromal interactions on the heterogeneity of response within breast cancer subtypes have just begun to be explored. This study focuses on patients with estrogen receptor-positive/human epidermal growth factor receptor 2-positive (ER+/HER2+) breast cancer receiving neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel predictive biomarkers by combining gene expression analysis and immunohistochemistry with pathologic response.MethodsWe performed gene expression profiling on pre-NAC+H tumor samples from responding (no or minimal residual disease at surgery) and non-responding patients. Gene set enrichment analysis identified potentially relevant pathways, and immunohistochemical staining of pre-treatment biopsies was used to measure protein levels of those pathways, which were correlated with pathologic response in both univariate and multivariate analysis.ResultsIncreased expression of genes encoding for stromal collagens, including Col10A1, and reduced expression of immune-associated genes, reflecting lower levels of total tumor-infiltrating lymphocytes (TILs), were strongly associated with poor pathologic response. Lower TILs in tumor biopsies correlated with reduced likelihood of achieving an optimal pathologic response, but increased expression of the Col10A1 gene product, colXα1, had greater predictive value than stromal abundance for poor response (OR = 18.9, p = 0.003), and the combination of increased colXα1 expression and low TILs was significantly associated with poor response in multivariate analysis. ROC analysis suggests strong specificity and sensitivity for this combination in predicting treatment response.ConclusionsIncreased expression of stromal colXα1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment.

Dataset Information

Clinical characteristics, tumor-infiltrating lymphocytes, and prognosis in HER2-low breast cancer: A comparison study with HER2-zero and HER2-positive disease.

Introduction

Methods

Results

Conclusions

Publications

Clinical characteristics, tumor-infiltrating lymphocytes, and prognosis in HER2-low breast cancer: A comparison study with HER2-zero and HER2-positive disease.

Similar Datasets

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