Parity and breastfeeding led to an accumulation of CD8-positive T cells that offered protection against future breast cancer in parous women, according to study results published in Nature.

Prior research has demonstrated a link between parity, lactation, and a reduction in the risk for breast cancer, particularly in triple-negative breast cancer.

Despite this recognized link, questions remained regarding the underlying immunologic mechanisms involved in breast cancer protection in parous women who breastfed after giving birth.

Sherene Loi, MBBS, PhD, Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues conducted preclinical research using mouse models, which demonstrated that pregnancy followed by breastfeeding induced an accumulation of CD8-positive T cells in murine mammary glands.

The accumulation of these T cells — which included cells with a tissue-resident memory-like phenotype — correlated with reductions in tumor growth and boosted intratumoral immune cell infiltration.

Loi and colleagues noted that the introduction of these protective T cells occurred only in cases where a complete cycle of lactation and involution was achieved.

Next, the researchers evaluated samples from women with triple-negative breast cancer. In a cohort of 734 women with parity status, including 656 with confirmed breastfeeding history, gene expression tumor infiltrate scores showed that parous women had significantly higher tumoral immune content overall in basal-like tumors than nulliparous women. Similar results were observed in parous women who breastfed compared to nulliparous women. Parous breastfeeding women also had significantly higher intratumoral CD8-positive T-cell density in basal-like tumors.

Loi and colleagues also examined data from a cohort of 270 women with a germline pathogenic variant who were diagnosed with early breast cancer following at least one full-term pregnancy. They found that breastfeeding patients had significantly longer overall survival following a diagnosis of breast cancer than patients who did not breastfeed.

“Women who have breastfed have more specialized immune cells that ‘live’ in the breast tissue for decades after childbirth. Women who breastfed had tumours with higher numbers of these protective T cells and, in some groups, they lived longer after diagnosis of breast cancer.”

 — Sherene Loi, MBBS, PhD, Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, Australia, and colleagues

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By Cameron Kelsall

Reference: https://www.nature.com/articles/s41586-025-09713-5

Disclosures: Loi declared financial ties to drugmakers. See study for details.

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