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A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, say the authors.

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, paxil and alcohol mixed PhD, of Cancer Council Victoria, Melbourne, Australia, and colleagues report on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online September 6 in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization — a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank [genome-wide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio [OR], 0.59), the team reports. Genetically-predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone-receptor-negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.  

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre/peri-menopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors note, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers report, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggest that  “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. The full list can be found with the original article. Dixon-Suen reported no relevant financial relationships. Several co-authors disclosed relationships with industry. The full list can be found with the original article.

Br J Sports Med. Published online September 6, 2022. Abstract

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at  [email protected]  or on Twitter:  @SW_MedReporter .

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