Exercise During Chemotherapy Reshapes Immune Cells in Breast Cancer Patients, Pilot Study Finds

A twelve-week programme of supervised aerobic and resistance training delivered while women were undergoing chemotherapy for early-stage breast cancer proved safe, feasible and strikingly acceptable to patients, according to a pilot study published in Supportive Care in Cancer. Beyond confirming that women can and will train through one of the most demanding phases of cancer treatment, the study offers some of the most detailed evidence yet that exercise measurably alters the immune system during chemotherapy, with exploratory signals pointing toward enhanced differentiation of cytotoxic T cells and protection against the metabolic disruption that commonly accompanies treatment.

The trial, known as FASTEX, was conducted by researchers at the Exercise Medicine Research Institute at Edith Cowan University in Perth, Australia, working with clinicians at Sir Charles Gairdner Hospital, Fiona Stanley Hospital and Joondalup Health Campus. Women with histologically confirmed breast cancer who were scheduled to receive neoadjuvant or adjuvant chemotherapy, with or without immunotherapy, were invited to take part. Rather than being randomly assigned, participants chose their own intervention: thirteen women opted for the supervised exercise programme, five chose a fasting-mimicking diet arm reported separately, and because no eligible participants volunteered for usual care, a convenience control group of six women was recruited to provide blood samples for biomarker comparison.

The exercise prescription was deliberately pragmatic. Sessions lasted roughly sixty minutes and combined a warm-up, fifteen to twenty minutes of aerobic work on a treadmill or stationary bike, twenty to twenty-five minutes of resistance training targeting the major upper- and lower-body muscle groups, and a cool-down. Participants were asked to attend two supervised sessions during chemotherapy weeks and three during non-treatment weeks, with intensity individually tailored to maintain a target rating of perceived exertion between twelve and sixteen on the Borg six-to-twenty scale. Loads and volumes were progressively increased, and by the end of the twelve weeks the average resistance training load had risen by ten to sixty per cent, with total training volume approximately doubling.

Feasibility was the study’s primary outcome, and the results were encouraging. Retention reached 84.6 per cent, with eleven of thirteen participants completing the programme; the two withdrawals were both related to travel rather than to the exercise itself. Attendance averaged 83.6 per cent and adherence to the prescribed sessions 77.9 per cent, both exceeding the pre-defined thresholds of 75 per cent. Most missed sessions were attributable to treatment-related side effects such as fatigue, gastrointestinal symptoms and pain, while session modifications were typically driven by medical considerations such as the presence of a PICC line or by comorbidities. Only one adverse event, a transient episode of mild hypotension in a participant with pre-existing hypertension, was recorded across the entire intervention.

The immunological findings formed the scientific core of the study. Using spectral flow cytometry on cryopreserved peripheral blood mononuclear cells, the researchers characterised T cell and natural killer cell subsets in fine detail, tracking differentiation, activation, senescence and exhaustion markers. Compared with controls, the exercising women showed a significantly greater increase in CD8-positive effector memory cells re-expressing CD45RA, known as EMRA cells, with a large effect size, alongside a significant reduction in CD8-positive naïve T cells. Signals toward significance were also observed for central memory CD8 cells, for CD8 cells expressing CD57, and for CD8 cells expressing PD-1, each of which shifted more in the exercise group than in the controls.

Interpreting these shifts requires care, and the authors were explicit about the alternatives. An expansion of EMRA and CD57-positive CD8 T cells could, in principle, indicate immunosenescence, the accumulation of terminally differentiated cells with limited proliferative capacity. However, EMRA cells commonly express high levels of cytotoxic machinery and can execute immediate effector functions, and PD-1, although classically an exhaustion marker, is also transiently upregulated during T cell activation. Because no changes were seen in other exhaustion markers such as CTLA-4 and TIM-3, the researchers suggest the pattern may instead reflect a functional shift toward a low-proliferative but highly cytotoxic effector state, consistent with preclinical work showing that muscle-derived metabolites such as lactate can promote cytotoxic differentiation of CD8 T cells.

Metabolic data added a second layer of interest. The control group showed a significant rise in fasting insulin over the study period while the exercise group did not, a between-group difference that reached statistical significance. Because glucose levels did not change in parallel, the authors interpret the insulin rise in controls as consistent with compensatory hyperinsulinaemia driven by emerging peripheral insulin resistance, a well-recognised consequence of chemotherapy that is linked to adiposity, inflammation, hormonal alteration and loss of muscle. Exercise, by enhancing skeletal muscle insulin sensitivity and GLUT4-mediated glucose uptake, may have blunted this trajectory, although the authors caution that the control group’s samples were not collected in a fasting state, a logistical constraint that limits firm conclusions.

Body composition and patient-reported outcomes rounded out the picture. Despite ongoing chemotherapy, the exercising women maintained stable body weight, fat mass and lean mass, with signals toward modest gains in lean mass of roughly 0.8 kilograms. This stability matters clinically, because chemotherapy typically drives fat gain and lean tissue loss, and higher adiposity after diagnosis predicts poorer breast cancer-specific and overall survival. On the questionnaire side, global quality of life measured by the EORTC QLQ-C30 improved significantly, rising by 16.7 points, with smaller improvements across physical, emotional and social functioning domains, and fatigue showed a signal toward improvement on the FACIT-F Trial Outcome Index. Participants rated the burden of the programme as very low and reported perceived benefits for well-being and treatment tolerance.

Seven participants received neoadjuvant chemotherapy, allowing a preliminary look at pathological complete response, the disappearance of invasive cancer in the resected specimen. Three of four exercising patients and all three controls achieved a complete response, a uniformly high rate that precludes any conclusion about whether exercise influenced treatment efficacy, particularly since the one non-responder had inflammatory breast cancer, a subtype associated with lower response rates. The authors stress that future studies should directly test whether exercise-induced immune modulation translates into improved therapeutic response.

The limitations of the pilot are substantial and the authors acknowledge them candidly. Participants self-selected into the exercise arm, raising the possibility that the programme appealed mainly to motivated women with the transport, time and physical capacity to attend supervised sessions, so feasibility in the broader population may be lower. The sample was small, the control group was a convenience sample of unequal size, menopausal status differed between groups at baseline, and chemotherapy regimens and blood sampling intervals varied. No functional immune assays or tumour infiltration analyses were performed, so it remains unknown whether the observed phenotypic changes alter immune cell behaviour in practice. Even so, the study’s comprehensive immune phenotyping, combined with concurrent metabolic, body composition and quality of life assessments, marks it as one of the most detailed portraits to date of what exercise does inside the bodies of women fighting breast cancer, and it lays the groundwork for the larger randomised trials that will determine whether training through chemotherapy can genuinely sharpen the immune system’s anti-tumour arsenal.

Subject of Research: Exercise training during chemotherapy for early-stage breast cancer and its effects on immune and metabolic outcomes

Article Title: Exploring the feasibility of exercise training during (neo)adjuvant chemotherapy in women with early-stage breast cancer: a pilot study examining immune and metabolic outcomes

Article References: Crespo-García, C., Bettariga, F., Taaffe, D. R., Campbell, J. P., Peddle-McIntyre, C. J., Jeffery, E., Redfern, A. D., Rinaldi, C. A., Galvao, D. A., & Newton, R. U. (2026). Exploring the feasibility of exercise training during (neo)adjuvant chemotherapy in women with early-stage breast cancer: a pilot study examining immune and metabolic outcomes. Supportive Care in Cancer, 34(10), Article 1013. https://doi.org/10.1007/s00520-026-11179-8

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11179-8

Keywords: breast cancer, chemotherapy, exercise oncology, CD8 T cells, immune modulation, insulin resistance, body composition, quality of life, cancer fatigue, pilot study, resistance training, aerobic exercise