San Antonio—Exercise may have a direct effect on breast tumor tissue in humans, according to a study presented at the 2016 San Antonio Breast Cancer Symposium. The study showed that a brief, preoperative exercise intervention in women with breast cancer sparked an upregulation of cellular pathways, including immune and cytokine–cytokine receptor interaction pathways.
Lead investigator Jennifer Ligibel, MD, the director of the Leonard P. Zakim Center for Integrative Therapies at Dana-Farber Cancer Institute, in Boston, said the findings provide “new insights into the biology through which exercise could impact breast cancer.”
Previous observational studies have identified an inverse relationship between exercise and breast cancer risk and prognosis (Menopause 2016 Oct 24. [Epub ahead of print], PMID: 27779567; Acta Oncol 2015;54[5]:635-654, PMID: 25752971). Animal studies provide support for this as well, Dr. Ligibel said, but “there have been very few studies in humans testing the direct impact of exercise on human breast cancer tissues.”
During the Preoperative Health & Body Study, Dr. Ligibel and her colleagues recruited 48 women with newly diagnosed, stage I to III breast cancer who were planning to undergo surgery at Dana-Farber Cancer Institute or Yale University Medical Center (abstract S5-05). The patients had to be engaging in less than 90 minutes per week of moderate or vigorous exercise. The investigators excluded women receiving neoadjuvant chemotherapy or endocrine therapy, any hormonally active agents or diabetes medications.
The patients received a baseline research biopsy and were randomly assigned to receive an exercise intervention or mind–body intervention until the time of surgery (Table). Fasting blood, questionnaires and anthropometric measures were collected at baseline and within three days before surgery. The investigators collected tumor tissue from the baseline research/diagnostic biopsy and took an excisional specimen at the time of breast surgery. The median time between enrollment and surgery was 3.6 weeks in the exercise group and 4.8 in the mind–body group.
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There was no difference in the primary end point—the effect on Ki-67—but there were changes in secondary end points. Patients in the exercise group experienced a significant decrease in leptin (–41.6 vs. 2.1 pg/mL; P=0.008) and a borderline decrease in insulin-like growth factor (IGF)-1 (–0.1 vs. 0 ng/mL; P=0.08). There was no significant change in other metabolic or inflammatory mediators, such as insulin, adiponectin or C-reactive protein, but “the changes in leptin and IGF-1 suggest a physiologic effect, despite the short duration of exercise intervention,” Dr. Ligibel said.
Further analysis revealed that 18 unique pathways, including pathways related to inflammation and immunity, were significantly upregulated in the exercise group, whereas no pathways were upregulated in the mind–body intervention group. The upregulated pathways in the exercise arm included cytokine–cytokine receptor interaction, NF-kappa B signaling, complement and coagulation cascade, natural killer cell–mediated cytotoxicity, antigen processing and presentation, and T-cell receptor signaling. The “upregulated pathways were consistent with those seen in animal models of exercise,” Dr. Ligibel said.
“In our gene expression analyses, we did not see any single genes that were differentially expressed, but we did see a physiologic effect of exercise on pathway regulation and an upregulation of 18 unique pathways,” Dr. Ligibel said. “These findings need to be validated in additional cohorts, and future work is needed to correlate exercise-induced changes in gene expression to protein production and, ultimately, to clinical outcomes.”
Commenting after the presentation, Frankie Ann Holmes, MD, a hematologist/oncologist at Texas Oncology-Houston Memorial City, pointed out that another study showed that a six-month exercise intervention could influence the genome-wide DNA methylation pattern in human adipose tissue (PLoS Genet 2013;9[6]:e1003572, PMID: 23825961). Dr. Holmes said that “the study identified epigenetic alterations—a lot of them—that could be a measurable outcome for something like this.”
—Kate O’Rourke
Drs. Ligibel and Holmes reported no relevant financial relationships.