Basal-like HR + /HER2- breast cancers show higher tumor-infiltrating lymphocytes and immune signatures with potential therapeutic implications

Hormone receptor-positive (HR + )/HER2-negative (HER2 - ) early breast cancers (BCs) are typically considered immunologically cold. However, combining immune checkpoint inhibitors (ICIs) with chemotherapy has shown to improve pathological complete response (pCR) in high-risk patients. Understanding the relationship between immune activation and tumor biology may help identify HR + /HER2 - BC patients most likely to benefit from such combinations. Baseline gene expression data from two neoadjuvant trials (GIADA and LETLOB) including HR + /HER2 - BC patients were analyzed. PAM50 intrinsic subtyping and relevant immune-related gene signatures were calculated. Tumor-infiltrating lymphocytes (TILs) were assessed on baseline samples. Among 109 tumors, PAM50 classified 44% as Luminal-B (LumB), 33% Luminal-A (LumA), 18% Basal-like, and 5% HER2-enriched. TIL levels (available for N = 101) were generally low (median 2; range 0-100), with higher levels in Basal-like BCs (p = 0.008). Basal-like BCs exhibited significantly higher levels of immune-related signatures (CD8 T-cells, Cytotoxic cells, IFN-γ, response to ICI + CT in GeparNuevo) and of PD-1, PD-L1, and PD-L2 genes. No differences were found between LumA and LumB subtypes. TILs and immune signatures showed a significant weak-to-moderate positive correlation with the basal-like signature. HR + /HER2- BCs that display both features of biological aggressiveness and enhanced immunogenicity may represent ideal candidates for the combination of ICI and chemotherapy.

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Publication Details

Journal
npj Breast Cancer
Published
2025-12-24
DOI
https://doi.org/10.1038/s41523-025-00886-w
Citations
1
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
1.05

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article

Basal-like HR + /HER2- breast cancers show higher tumor-infiltrating lymphocytes and immune signatures with potential therapeutic implications

Katia Cagossi, Federica Miglietta, Simon Spazzapan, Daniele Generali et al.
1 citations
npj Breast Cancer
Cancer Immunotherapy and Biomarkers
1.05
article

Basal-like HR + /HER2- breast cancers show higher tumor-infiltrating lymphocytes and immune signatures with potential therapeutic implications

Katia Cagossi, Federica Miglietta, Simon Spazzapan, Daniele Generali, Grazia Maria Vernaci, Valentina Guarneri, Rocco Cappellesso, Francesca Schiavi, Tommaso Giarratano, Silvio Bicciato, Antonino Musolino, Michele Bottosso, Enrico Tagliafico, Federico Piacentini, Anna Tosi, Aleix Prat, Laia Paré, Gaia Griguolo, Maria Vittoria Dieci
article en
1 citations

Abstract

Hormone receptor-positive (HR + )/HER2-negative (HER2 - ) early breast cancers (BCs) are typically considered immunologically cold. However, combining immune checkpoint inhibitors (ICIs) with chemotherapy has shown to improve pathological complete response (pCR) in high-risk patients. Understanding the relationship between immune activation and tumor biology may help identify HR + /HER2 - BC patients most likely to benefit from such combinations. Baseline gene expression data from two neoadjuvant trials (GIADA and LETLOB) including HR + /HER2 - BC patients were analyzed. PAM50 intrinsic subtyping and relevant immune-related gene signatures were calculated. Tumor-infiltrating lymphocytes (TILs) were assessed on baseline samples. Among 109 tumors, PAM50 classified 44% as Luminal-B (LumB), 33% Luminal-A (LumA), 18% Basal-like, and 5% HER2-enriched. TIL levels (available for N = 101) were generally low (median 2; range 0-100), with higher levels in Basal-like BCs (p = 0.008). Basal-like BCs exhibited significantly higher levels of immune-related signatures (CD8 T-cells, Cytotoxic cells, IFN-γ, response to ICI + CT in GeparNuevo) and of PD-1, PD-L1, and PD-L2 genes. No differences were found between LumA and LumB subtypes. TILs and immune signatures showed a significant weak-to-moderate positive correlation with the basal-like signature. HR + /HER2- BCs that display both features of biological aggressiveness and enhanced immunogenicity may represent ideal candidates for the combination of ICI and chemotherapy.

npj Breast CancerVol. 12(1)
University of Modena and Reggio Emilia (IT), University of Padua (IT), University of Trieste (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Istituto Oncologico Veneto (IT), Hospital Clínic de Barcelona (ES), National Cancer Institute (UA), Oryzon Genomics (Spain) (ES), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Istituti Ospitalieri di Cremona (IT), Universitat de Barcelona (ES), University of Bologna (IT)
Ministero della Salute, Università degli Studi di Padova, Associazione Italiana per la Ricerca sul Cancro
Good health and well-being
Openalex Percentile: Top 15%
Cancer Immunotherapy and Biomarkers
1.05
DOIOpen Access PDFOpenAlex
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