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The effect requires a full lactation–involution cycle, and parous women’s primary TNBC shows greater T-cell infiltration and better clinical outcomes across preclinical models and over 1,000 patient 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does parity relate to CD8+ T cells in normal breast tissue?","Question",{"text":63,"@type":64},"Parity is associated with increased numbers of CD8+ T cells, including cells with an tissue-resident-memory-like phenotype in human normal breast tissue.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role do pregnancy, lactation, and involution play in mouse tumour outcomes?",{"text":68,"@type":64},"In mouse models, pregnancy followed by lactation and involution drives CD8+ T-cell accumulation in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune infiltration.",{"name":70,"@type":61,"acceptedAnswer":71},"Is CD8+ T-cell-mediated protection observed after any stage of reproductive changes?",{"text":72,"@type":64},"No. CD8+ T-cell-dependent tumour control is observed only after a complete cycle of lactation and involution, and it is abolished by CD8+ T-cell 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 |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41586-025-09713-5](https://doi.org/10.1038/s41586-025-09713-5)\u003Cbr>Received: 2 August 2024 Accepted: 6 October 2025 Published online: 20 October 2025 Open access\u003Cbr> Check for updates | Balaji Virassamy1,2,52, Franco Caramia1,2,52, Peter Savas1,2,52, Michael A. Harris1,2,52, Jia-Wern Pan3, Jianan Wang1,2, Emmaline Brown1, Megan M. R. O’Malley1,2, Courtney T. van Geelen1,2, Michael Hun1,2, Thomas N. Burn4, Sneha Sant1, Jamieson D. Ballan1,2, Jasmine Kay1,2,\u003Cbr>Luis E. Lara Gonzalez1,2, Kylie Clarke1, Han Xian AwYeang1,2, Rejhan Idrizi1,2, Metta Jana1,2, Damon J. Challice1, Roberto Salgado1,5, Heather Thorne1,2, kConFab consortium*,\u003Cbr>Cathie Poliness6, Sophie Nightingale6, Soo-Hwang Teo3, Terence P. Speed7, Jane Visvader8,9, Paul J. Neeson1,2, Phillip K. Darcy1,2, Laura K. Mackay4 ✉ & Sherene Loi1,2 ✉\u003Cbr>Parity and breastfeeding reduce the risk of breast cancer, particularly triple-negative breast cancer (TNBC)1,2, yet the immunological mechanisms underlying this protection remain unclear. Here we show that parity is associated with increased numbers of CD8+ T cells, including cells with atissue-resident-memory-like phenotype within human normal breast tissue. In mouse models, pregnancy followed by lactation and involution drove the accumulation of CD8+ T cells in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune cell infiltration, effects that were abrogated by CD8+ T cell depletion. Importantly, this CD8+ T-celldependent tumour control was observed only after a complete cycle of lactation and involution. Consistent with this, primary triple-negative breast cancers from parous women exhibited greater T cell infiltration and improved clinical outcomes. Together, these findings, spanning preclinical models andover 1,000 patient samples, provide insights into how reproductive history shapes breast immunity, positioning CD8+ T cells as key mediators of parity-associated protection and informing strategies for both the prevention and the treatment of breast cancer. |  |\n| It is widely recognized that parity and lactation are associated with a |  | anti-tumour responses and is associated with reduced breast cancer |\n| reduced long-term risk of breast cancer1,2. Parity is thought to protect by |  | recurrence8,10,11. We also showed that TRM-like cells were present in both |\n| reshaping mammary epithelial cell differentiation and growth pathways |  | breast tumoursand cancer-unaffected normal breast tissue, implicat- |\n| that occur during pregnancy, lactation and involution, thereby reducing |  | ing them in treatment response and long-term immune surveillance |\n| susceptibility to malignant transformation overtime3–5. While parity |  | of the breast. |\n| has been associated with a decreased risk of hormone-receptor-positive |  | Post-partum, immune cell populations in mammary tissue undergo |\n| breast cancer, breastfeeding appears to confer amore specific reduc- |  | considerable modulation: pregnancy and lactation are followed by |\n| tion in the risk of triple-negative breast cancer (TNBC)1,6. The cellular |  | widespread apoptosis and tissue remodelling in the process known as |\n| and molecular mechanisms underlying this association are unclear. |  | involution12,13. Changes in immune subsets, such as increased natural |\n| Deeper understanding could enable new subtype-specific prevention |  | killer T (NKT) cells in the post-involution mammary gland, suggest |\n| and treatment strategies for breast cancer. This could be particularly |  | a parity-induced immune surveillance mechanism14. Furthermore, |\n| relevant for women at higher risk ofTNBC, such as those who carry |  | circulating T cells increases in parous women have been observed to |\n| germline pathogenic variants, or for groups with poorer outcomeseven |  | persist for months post-partum andarethou","cbCaiifCEUKj8hOj","https://ap.wps.com/l/cbCaiifCEUKj8hOj","pdf",20285419,36,"English","# Article Summary\n## Parity and breastfeeding reduce breast cancer risk\n## Human evidence: CD8+ T-cell increases in normal breast tissue\n## Mouse models: lactation–involution drives CD8+ T-cell accumulation\n## Dependence on CD8+ T cells and requirement of full cycle\n## Clinical relevance in primary TNBC from parous women","[{\"question\":\"How does parity relate to CD8+ T cells in normal breast tissue?\",\"answer\":\"Parity is associated with increased numbers of CD8+ T cells, including cells with an tissue-resident-memory-like phenotype in human normal breast tissue.\"},{\"question\":\"What role do pregnancy, lactation, and involution play in mouse tumour outcomes?\",\"answer\":\"In mouse models, pregnancy followed by lactation and involution drives CD8+ T-cell accumulation in the mammary gland, coinciding with reduced tumour growth and increased intratumoural immune infiltration.\"},{\"question\":\"Is CD8+ T-cell-mediated protection observed after any stage of reproductive changes?\",\"answer\":\"No. CD8+ T-cell-dependent tumour control is observed only after a complete cycle of lactation and involution, and it is abolished by CD8+ T-cell depletion.\"}]","Parity and lactation induce T-cell-mediated breast cancer protection | PDF",1790746914,91]