Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis

Abstract

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m² BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I² = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Keywords: Body fatness; breast cancer survival; evidence grading; systematic review; weight change.

FIGURE 1

Flow chart of study selection process

FIGURE 2

Linear and nonlinear dose‐response meta‐analyses of postdiagnosis body mass index and all‐cause mortality. Forest plot shows the linear dose‐response results for postdiagnosis body mass index (BMI) and all‐cause mortality from the inverse variance DerSimonian‐Laird random‐effects model. Diamond represents the summary relative risk (RR) estimate and its width as the 95% confidence interval (CI). Each square represents the RR estimate of each study and the horizontal line across each square represents the 95% CI of the RR estimate. The increment unit was per 5 kg/m². Nonlinear curve was estimated using restricted cubic spline regression with three knots at 10th, 50th and 90th percentiles of distribution of the exposure and pooled in random‐effects meta‐analysis. BMI at 20 kg/m² was selected as reference. The table shows selected BMI values and their corresponding RR (95% CI) estimated in the nonlinear dose‐response meta‐analysis.

FIGURE 3

Linear and nonlinear dose‐response meta‐analyses of postdiagnosis body mass index and breast cancer‐specific mortality. Forest plot shows the linear dose‐response results for postdiagnosis body mass index (BMI) and breast cancer‐specific mortality from the inverse variance DerSimonian‐Laird random‐effects model. Diamond represents the summary relative risk (RR) estimate and its width as the 95% confidence interval (CI). Each square represents the RR estimate of each study and the horizontal line across each square represents the 95% CI of the RR estimate. The increment unit was per 5 kg/m². Nonlinear curve was estimated using restricted cubic spline regression with three knots at 10th, 50th and 90th percentiles of distribution of the exposure and pooled in random‐effects meta‐analysis. BMI at 20 kg/m² was selected as reference. The table shows selected BMI values and their corresponding RR (95% CI) estimated in the nonlinear dose‐response meta‐analysis.