Reducing Inflammation in Breast Cancer Survivors: The Impact of Exercise and Weight Loss

I have recently read a study called WISER Survivor Trial: Exploring the Effects of Exercise and Weight Loss on Inflammation in Breast Cancer Survivors.

This study was done as obesity and physical inactivity are known to increase the risk of breast cancer recurrence and cardiovascular disease. The WISER Survivor Trial investigated the role of exercise training, weight loss, and their combination in reducing inflammation, a common factor in these conditions.

The WISER Survivor Trial was a four-arm randomised controlled trial involving 318 breast cancer survivors who were overweight or obese. Participants were randomly assigned to one of the following groups:

• Exercise Alone

• Weight Loss Alone

• Exercise plus Weight Loss

• Control

Inflammation biomarkers, including C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were measured at baseline and after 12 months of intervention.

The study's results showed that The Exercise plus Weight Loss group showed a significant reduction in CRP levels compared to the Control, Weight Loss Alone, and Exercise Alone groups. However, there were no significant changes in SAA, ICAM-1, or VCAM-1 levels in any of the groups.

The findings of the WISER Survivor Trial suggest that a combination of exercise training and weight loss may be effective in reducing inflammation in breast cancer survivors who are overweight. This is particularly relevant as elevated CRP levels have been associated with an increased risk of breast cancer recurrence and cardiovascular events.

The mechanisms underlying the reduction in CRP levels are not fully understood but may involve improvements in insulin sensitivity, reduction in adipose tissue inflammation, and changes in immune function. Further research is needed to elucidate these mechanisms and to determine the long-term effects of exercise and weight loss on inflammation and breast cancer outcomes.

The WISER Survivor Trial provides important evidence for the potential benefits of a combination of exercise and weight loss in reducing inflammation in breast cancer survivors. This study highlights the need for future research to optimise interventions and improve this population's overall health and well-being.

Inflammation as a Step in Cancer Development

Chronic inflammation is recognised as a common factor in the pathophysiology of several obesity-related medical problems, including cancer. Obesity leads to low-grade chronic inflammation that affects multiple organs in the body, including white adipose tissue, liver, intestines, pancreas, muscle, and nervous system. Studies have shown that obesity-associated inflammation starts with excess energy intake (overeating), leading to an energy imbalance. This imbalance activates various signalling pathways in metabolic tissues, including the white adipose tissue, liver, and muscle. As a result, there is an increased production of inflammatory mediators and inflammatory cytokines (molecules).

In the context of breast cancer, excess energy is stored as triglycerides in adipocytes. Too much energy leads to the expansion of adipocytes via hypertrophy (an increase in size) and hyperplasia (an increase in number). However, studies have shown that adults have a finite number of adipose stem cells, thus limiting adipocyte hyperplasia. This suggests that adipose tissue expansion is primarily due to adipocyte hypertrophy. Therefore, adipocyte hypertrophy is believed to play a larger role in obesity-associated inflammation. When adipocytes undergo hypertrophy, they produce more inflammatory molecules. This is due to mechanical stress from expansion and decreased oxygen supply (these cells are in the stress mode).

It is a belief that obesity-associated inflammation is a major driver of the increased risk of breast cancer and poor breast cancer prognosis in obese women. In obese postmenopausal women, there is a positive correlation between circulating C-reactive protein (CRP)—a marker of inflammation—and breast cancer risk. CRP levels are also associated with shorter disease-free survival.

Similar findings were found in people who develop lung cancer who are not smokers. Exposure to air pollution, particularly PM2.5 particulate matter, increases the risk of lung cancer in non-smokers due to chronic inflammation.

• PM2.5 particles enter the small airways of the lungs, where they trigger an immune response involving macrophages, cells that engulf foreign particles.

• In non-smokers with existing EGFR mutation (which may occur in up to half a million people), macrophages produce interleukin-1 beta, which promotes an inflammatory environment.

• This inflammation activates pre-existing mutant cells, causing them to proliferate and potentially form cancerous tumours.

This mechanism of carcinogenesis is different from that observed in smokers, where exposure to mutagenic substances in tobacco smoke directly damages DNA.

The link between air pollution and lung cancer has been established through epidemiological studies showing an increased incidence of the disease in areas with higher levels of air pollution. Researchers have also identified a correlation between air pollution and the presence of EGFR-mutated lung cancer, a type commonly found in non-smokers.

Animal studies have provided further evidence for the role of inflammation in air pollution-induced lung cancer. Mice exposed to PM2.5 particles developed tumours when their skin was irritated with surgical staples, suggesting that chronic irritation can promote the growth of pre-existing mutant cells.

I also believe that exercise alone is likely to cause less inflammation, both in people who are obese and those who are normal weight. Hence, regular moderate exercise of 5 times per week (30min per day or 150min per week) is shown to decrease the risk of developing breast cancer by 20%.