Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis

Abstract

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded 'limited-suggestive' likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.

Keywords: breast cancer survival; evidence grading; expert panel judgement; physical activity; systematic review.

FIGURE 1

Flow chart of study selection process

FIGURE 2

Summary hazard ratio estimate (95% CI) of (A) all‐cause mortality for every 10 MET‐h/week of recreational physical activity after diagnosis, (B) all‐cause mortality for the highest compared to the lowest level of recreational physical activity after diagnosis, (C) breast cancer‐specific mortality for every 10 MET‐h/week of recreational physical activity after diagnosis, (D) breast cancer‐specific mortality for the highest compared to the lowest level of recreational physical activity after diagnosis, (E) recurrence for every 10 MET‐h/week of recreational physical activity after diagnosis and (F) recurrence for the highest compared to the lowest level of recreational physical activity after diagnosis. Forest plot shows results from the random effects model. Diamond represents the summary hazard ratio. Each square represents the hazard ratio estimate of each study and the horizontal line across each square represents the 95% confidence interval (CI) of the hazard ratio estimate. ABCPP (Beasley 2012) included data from three US cohorts that is, LACE, NHS, WHEL and one Chinese cohort SBCSS. For the CPS‐II Nutrition Cohort (Maliniak 2018), the HR estimates for the two age groups reported were combined using fixed effects models before inclusion in the meta‐analysis

FIGURE 3

Nonlinear association between recreational physical activity after diagnosis and (A) all‐cause mortality and (B) breast cancer‐specific mortality. The curves show the nonlinear dose–response associations between recreational physical activity after diagnosis and (A) all‐cause mortality and (B) breast cancer‐specific mortality, estimated using restricted cubic spline regression with three knots at 10th, 50th and 90th percentiles of distribution of the exposure and pooled with random‐effects meta‐analysis. Recreational physical activity at 0 metabolic equivalent of task (MET) was chosen as reference.