ArticleCarcinogenesis2025
The impact of reproductive factors on breast tumor and normal-adjacent tissue immune profile from menarche to menopause.
Article in Carcinogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Icariin: Multi-target natural products for the multi-stage prevention and treatment of breast cancer (Review).Molecular and clinical oncology · 2026Review
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Authors and funding
10 authors.
Funding
Abstract
Reproductive factors and sex hormones are tightly linked to systemic immunity. However, no studies have examined whether reproductive factors and hormone use modulate the immune microenvironment of breast tissue. We prospectively evaluated the associations of reproductive factors and exogenous hormone use with breast tumor and normal-adjacent tissue immune cell markers among 935 breast cancer cases in the Nurses' Health Studies. We deconvoluted immune cell abundance using CIBERSORTx and derived gene expression signatures of markers for immune checkpoint (PD1, PDL1, and CTLA4), co-regulatory signal and antigen presentation (MHC class I/ II and T cell receptor), and mammary cytokine signaling. Linear regression was used adjusting for confounders. Patterns of associations between reproductive factors and immune profile differed between tumor and normal-adjacent tissues and by estrogen receptor (ER) status. Tumors from postmenopausal women had significantly higher pro-inflammatory cytokine signaling and antigen presentation compared with tumors from premenopausal women (FDR ≤ 0.05). Several reproductive factors were nominally associated with immune profiles of normal-adjacent tissues. For example, parous women had higher CD8 T cell infiltration, higher PDL1 expression, and lower cytokine signaling (P ≤ .05); women who ever breastfed showed higher infiltration of NK cells and T helper cells in normal-adjacent tissue of ER+ tumors but lower infiltration of CD8 T cell and monocyte, and higher expression of cytokine signaling in normal-adjacent tissue of ER- tumors (P ≤ .05). Our study demonstrates for the first time in a large epidemiologic study that reproductive factors may influence breast tumor immune microenvironment and sheds light on potential immune regulation for breast cancer prevention.
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