ArticlePloS one2016
A Stromal Immune Module Correlated with the Response to Neoadjuvant Chemotherapy, Prognosis and Lymphocyte Infiltration in HER2-Positive Breast Carcinoma Is Inversely Correlated with Hormonal Pathways.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 10 citations in OpenAlex.
- Tumor-infiltrating lymphocytes display prognostic signatures associated with chemotherapy response in TNBC patients.iScience · 2026Article
- The interplay between the immune response and neoadjuvant therapy in breast cancer.Frontiers in oncology · 2025Review
- A generalized non-linear model predicting efficacy of neoadjuvant therapy in HER2+ breast cancer.iScience · 2023Article
- Machine learning models based on immunological genes to predict the response to neoadjuvant therapy in breast cancer patients.Frontiers in immunology · 2022Article
- Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.Frontiers in immunology · 2022Article
- LRP8 is overexpressed in estrogen-negative breast cancers and a potential target for these tumors.Cancer medicine · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHER2-positive breast cancer (BC) is a heterogeneous group of aggressive breast cancers, the prognosis of which has greatly improved since the introduction of treatments targeting HER2. However, these tumors may display intrinsic or acquired resistance to treatment, and classifiers of HER2-positive tumors are required to improve the prediction of prognosis and to develop novel therapeutic interventions.
methodsWe analyzed 2893 primary human breast cancer samples from 21 publicly available datasets and developed a six-metagene signature on a training set of 448 HER2-positive BC. We then used external public datasets to assess the ability of these metagenes to predict the response to chemotherapy (Ignatiadis dataset), and prognosis (METABRIC dataset).
resultsWe identified a six-metagene signature (138 genes) containing metagenes enriched in different gene ontologies. The gene clusters were named as follows: Immunity, Tumor suppressors/proliferation, Interferon, Signal transduction, Hormone/survival and Matrix clusters. In all datasets, the Immunity metagene was less strongly expressed in ER-positive than in ER-negative tumors, and was inversely correlated with the Hormonal/survival metagene. Within the signature, multivariate analyses showed that strong expression of the "Immunity" metagene was associated with higher pCR rates after NAC (OR = 3.71[1.28-11.91], p = 0.019) than weak expression, and with a better prognosis in HER2-positive/ER-negative breast cancers (HR = 0.58 [0.36-0.94], p = 0.026). Immunity metagene expression was associated with the presence of tumor-infiltrating lymphocytes (TILs).
conclusionThe identification of a predictive and prognostic immune module in HER2-positive BC confirms the need for clinical testing for immune checkpoint modulators and vaccines for this specific subtype. The inverse correlation between Immunity and hormone pathways opens research perspectives and deserves further investigation.
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