A review of research on the intersection between breast cancer and cardiovascular research in the Women’s Health Initiative (WHI)

Abstract

Both obesity and metabolic syndrome are linked to increased incidence of type 2 diabetes, cardiovascular disease (CVD), and cancers of the breast (post-menopausal), and other obesity-related cancers. Over the past 50 years, the worldwide prevalence of obesity and metabolic syndrome has increased, with a concomitant higher incidence of associated co-morbidities and mortality. The precise mechanism linking metabolic syndrome to increased cancer incidence is incompletely understood, however, individual components of metabolic syndrome have been linked to increased breast cancer incidence and worse survival. There is a bidirectional relationship between the risk of CVD and cancer due to a high burden of shared risk factors and higher rates of CVD among cancer survivors, which may be impacted by the pro-inflammatory microenvironment associated with metabolic syndrome and cancer-directed therapies. The Women’s Health Initiative (WHI) is an excellent resource to study a dual relationship between cancer and CVD (cardio-oncology) with extensive information on risk factors and long-term outcomes. The purpose of this review is to provide an overview of research on cardio-oncology conducted utilizing WHI data with focus on studies evaluating both breast cancer and CVD including shared risk factors and outcomes after cancer. The review also includes results on other obesity related cancers which were included in the analyses of breast cancer, articles looking at cancer after heart disease (reverse cardio-oncology) and the role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) as a shared risk factor between CVD and cancer. A summary of pertinent WHI literature helps to delineate the direction of future research evaluating the relationship between CVD and other cancer sites, and provides information on the opportunity for other novel analyses within the WHI.

Effects of lipid extract from blue mussel (Mytilus edulis) on gut microbiota, and its relationship with glycemic traits in type 2 diabetes mellitus patients: a double-blind randomized controlled trial

“…29 Compared with healthy subjects, higher Turicibacter levels were observed in patients with metabolic syndrome, 30 a disease associated with a high risk of T2DM. 31 In addition, high dietary intake of fat is associated with decreased gut Turicibacter in mice. 32…”

Combined Aerobic and Resistance Training Improves Body Composition, Alters Cardiometabolic Risk, and Ameliorates Cancer-Related Indicators in Breast Cancer Patients and Survivors with Overweight/Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…BC patients and survivors with concurrent overweight/obesity tend to demonstrate lipid metabolism impairments, enhancing the risk of developing CVD (Raychaudhuri et al, 2022). Thus, the relationship between lipid profile and obesity among BC survivors has been widely investigated (de Jesus et al, 2022;Okekunle et al, 2022;Vasseur and Guillaumond, 2022).…”

The impact of poor metabolic health on aggressive breast cancer: adipose tissue and tumor metabolism

“…Beyond BMI, other host variables may better predict breast cancer risk than the amount of body fat and may indicate the importance of developing tools to routinely assess metabolic health before diabetes develops ( 25 , 59 ). Adipose distribution often changes after menopause, when women experience more visceral adiposity or central obesity, reflected by a greater waist-to-hip ratio.…”