New explanations for why having children and breastfeeding might reduce triple-negative breast cancer (TNBC) risk raise questions about this link that are worth exploring in further research, experts said.

Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, described her data showing the observation that childbirth and breastfeeding protect against TNBC may be due to long-lived “resident” T cells being left behind in the breast and body, reducing the risk for cancer and boosting defenses against the disease.

Loi presented her research at the European Society for Medical Oncology (ESMO) Annual Meeting 2025 on October 19, with the results simultaneously published in Nature.

“Our research opens up a new area of biology, and…now we can potentially move to understanding how we can harness that for women who do not breastfeed or who remain nulliparous,” she said during a press conference at the meeting.

Can T Cells Protecting Against Breast Cancer Be Used in New Vaccinations and Immunotherapies?

Loi suggested the results could point towards potential vaccinations against TNBC based on how the resident T cells are targeting cancer cells, as well as novel immunotherapies and strategies to avoid interventions that interfere with lymphocytes.

She also emphasized that the findings underline the importance of collecting reproductive history, including the duration of breastfeeding, in all future breast cancer immuno-oncology trials.

But for today, “Now we have more impetus to make breastfeeding more acceptable and feasible in many workplaces and countries around the world, because obviously there are many barriers to women breastfeeding,” Loi told Medscape Medical News.

Ann H. Partridge, MD, MPH, director of the Young and Strong Program for Young Women with Breast Cancer at the Dana-Farber Cancer Institute, Boston, who was not involved in the study, described the findings as “really exciting results that can help us to understand why we see what we are seeing clinically from a biologic basis.”

She added that the concept of resident T cells protecting against breast cancer is “a really cool area,” and “if we could bottle that and give that to patients, wouldn’t that be cool?”

“We are doing that to some degree with our immunotherapies,” so the question becomes, “How do we do that better? How do we amp them up? How do we give them to women that don’t have children? These are all the directions you want to think about.”

Why Does Breastfeeding Cause Resident Memory T Cells to Become Resident?

Benjamin Fairfax, MD, PhD, professor of cancer immunogenetics, Department of Oncology, University of Oxford, Oxford, England, who was not involved in the study, served as the discussant in the session where the new research was presented.

It is “always very difficult” to tease out cause and effect in investigations such as these due to numerous “sociodemographic connotations associated with breastfeeding and nonbreastfeeding,” he said during the press conference at ESMO 2025.

“That’s why the murine models used certainly would support the hypothesis that this is breastfeeding” that’s having the effect, Fairfax added. “It’s always very difficult in human studies, though, to completely regress out these confounding factors.”

“What I would be particularly interested in, though, is the trigger of why breastfeeding causes the resident memory T cells to become resident,” he continued. One explanation is that it is a protective response, probably towards the infant, “but we don’t know, and I think that’s going to be really an interesting area to explore.”

He pointed to a recent study in women with cytomegalovirus comparing those who transmitted the virus to their infant via the breastmilk and those who did not. The researchers showed that nontransmitter mothers had a higher frequency of resident memory CD8+ T cells in their breast milk than transmitters, and that resident memory T cell frequency was inversely correlated with breast milk viral load.

Fairfax asked, “Could this be clinically leveraged?” He added, “It makes us wonder, what is the trigger for this residency? Is it the cycle of lactation and involution, or is it there are pathogens or microbiome alterations which potentially provide a secondary trigger?”

Moreover, could type I interferon signaling with immune checkpoint blockade enhance tissue retention? he asked.

There could also be implications for how women with breast cancer respond to therapy, Laura J. Esserman, MD, MBA, Alfred A. de Lorimier Endowed chair in general surgery and director of the UCSF Breast Care Center, San Francisco, told Medscape Medical News.

“Could this be associated with more of an immune phenotype?” she wondered. “I think that’s exciting,” as if so, it could be that women with resident T cells following breastfeeding are “much more likely to be responsive to immunotherapy.”

At this stage, the findings remain hypothesis-generating, however; Esserman underlined.

The conclusions are “not definitive till you start looking in people,” she said, “because our bodies are different, and we change over time.” 

Overall, Esserman believes that what Loi and colleagues have really “proposed is that we just do a much better job of collecting data so that we can start to analyze these hypotheses.”

Why Is TNBC Prevalence Increasing?

1 in 7 women will receive a diagnosis of breast cancer in their lifetime, and this rate is increasing, particularly among younger women, Loi said at the press conference.

“Why is this so?” she asked, “and how can we prevent breast cancer?”

She said that older studies showed that rates of breast cancer were very high in women who were nonchildbearing, and those findings have been reproduced in the modern era, demonstrating that women who have children and breastfeed for at least 6 months have a lower risk of developing breast cancer, specifically TNBC, the most aggressive form of the disease.

“But we don’t exactly know why,” Loi continued. “We’ve always thought that this has been related to hormones and to changes in the breast post-pregnancy and during breastfeeding. We’ve never really thought about how the immune system is acting in this context.”

Nevertheless, it is known that TNBC tumors contain higher quantities of immune infiltrate — predominantly CD8+ T cells, including those with a resident (CD103+) phenotype — compared with other forms of breast cancer, she explained in her presentation.

Higher quantities of this infiltrate are associated with a better prognosis, as well as greater responses to chemotherapy and immunotherapy, Loi noted. She also pointed out that the immune checkpoint inhibitor pembrolizumab is part of the standard of care for TNBC, thus “reinforcing the role of the immune system in the biology of this disease.”

What Did the Researchers Learn From Using Mouse Models?

Loi and colleagues conducted a series of experiments in the laboratory, the first of which showed that, in normal human breast tissue samples unaffected by cancer, parity was associated with increased numbers of T cells, including CD8+ and CD103+ cells, located towards the ductal epithelium.

Turning next to murine mammary gland tissue, they were able to demonstrate the same finding, that T cell abundance increased with parity. They also found that, when they implanted tumor cells into mice mammary glands, the tumors in mice that had breastfed and undergone involution grew slower than those in virgin mice.

“And importantly, when we removed the T cells, this protection was lost,” Loi noted in the press conference.

Finally, the researchers looked at data on more than 1000 women from around the world, including 634 from Malaysia and 270 from Australia, who developed breast cancer after their last child. This revealed that breastfeeding was associated with improved survival, as well as higher immune cell infiltration, after adjustment for other prognostic factors.

These results, Loi said, suggest that “reproductive history — pregnancy and breastfeeding — shapes long-term immune protection in women.”

The study was funded by the Breast Cancer Research Foundation and the Australian National Health and Medical Research Council.

Loi declared having relationships with AstraZeneca, Daiichi Sankyo, Novartis, Roche Genentech, BMS, Eli Lilly, Gilead Sciences, MSD, Amaroq Therapeutics, Mersana Therapeutics, Domain Therapeutics, Menarini Asia-Pacific, Bicycle Therapeutics, and Nektar Therapeutics.

Fairfax declared having relationships with Roche, Pathios Therapeutics, Immunocore, T-CypherBio, and GSK.

Esserman declared having relationships with Blue Cross Medical and Quantum Leap Healthcare.