Obesity may raise the risk of postmenopausal breast cancer more sharply in women with cardiovascular disease, according to a European study analyzing data from 168,527 women.
Investigators followed participants from two large prospective cohorts—the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank—for a median of 10.7 years in EPIC and 10.9 years in UK Biobank. At baseline, all participants were free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D). During follow-up, 6,847 women developed breast cancer.
Among women with CVD, each approximately 4.5 kg/m² increase in body mass index (BMI)—equivalent to 1 standard deviation—was associated with a 31% higher risk of postmenopausal breast cancer (hazard ratio, 1.31; 95% CI, 1.16–1.47). In women without CVD, the same BMI increase was associated with a 13% higher risk (hazard ratio, 1.13; 95% CI, 1.11–1.16).
The study found that CVD appeared to amplify the association between adiposity and breast cancer risk. While both obesity and CVD are independent risk factors, their combination resulted in more breast cancer cases than expected. The joint effect of overweight or obesity (BMI more than 25 kg/m²) and CVD resulted in 1.53 additional cases of breast cancer per 1000 person-years (95% CI, 0.35–2.71) beyond the expected incidence based on their individual risks.
Researchers also examined whether T2D modified the relationship between BMI and breast cancer risk. Although women with T2D and higher BMI had increased risk (hazard ratio, 1.20; 95% CI, 1.06-1.36), this association did not differ significantly from that in women without T2D (P for interaction = .33). No excess joint risk was observed between obesity and T2D.
Analyses were adjusted for a wide range of confounders, including age, center, height, age at menarche, parity, age at first birth, oral contraceptive use, menopausal hormone therapy use, smoking status, alcohol consumption, physical activity, healthy diet score, educational level, and family history of breast cancer (available in UK Biobank). Duration of CVD and T2D was modeled as a time-varying covariate.
Sensitivity analyses confirmed the findings. Adjustments for use of metformin and statins in UK Biobank, exclusion of breast cancer cases diagnosed within 1 year of cardiometabolic disease diagnosis, and stratification by hormone therapy use and cancer stage did not materially alter the results.
In both cohorts, women with higher BMI had lower physical activity levels, poorer diet quality, and more comorbidities such as hypertension, highlighting a clustering of cardiometabolic risk factors.
The authors proposed that systemic inflammation, immune suppression, and hormonal changes associated with both obesity and CVD may underlie the enhanced risk in affected women. They emphasized the importance of managing body weight in postmenopausal women, particularly those with CVD.
The study did not assess whether risk varied by breast cancer subtype or hormone receptor status. The authors recommended future research in this area and highlighted the need for integrated prevention strategies that target both obesity and cardiovascular health in aging women.
The authors reported no conflicts of interest.
Source: Cancer
