Obesity may accelerate how early breast cancer spreads in women, according to new research from the University of Oklahoma that identifies specific biological changes in tumour cells and their surrounding tissue.
How obesity changes the cellular environment
The study, led by assistant professor Bethany Hannafon at the university’s College of Medicine, examined tissue from women with obesity and found that their cancer cells were undergoing unique alterations that appeared to help them survive and thrive under stress. The changes were observed in both the tumours themselves and the cells around them, creating an environment more favourable to invasion.
A key discovery was raised levels of an enzyme called Sulfatase 2 (SULF2) in the tumour cells of women with obesity. This enzyme, a protein that accelerates chemical reactions in the body, has previously been linked to cancers of the breast, lung, liver and other organs. The researchers said it is thought to play a role in cancer progression by modifying the extracellular matrix and cell signalling, though further work is needed to determine exactly how it contributes to invasive breast cancer. “This could be why women with obesity are at higher risk for invasive breast cancer,” Hannafon said in a statement.
The area immediately surrounding the cancer was also more inflamed in women with obesity, with immune cells arriving and inadvertently speeding up tumour growth. While these cells normally fight disease, tumours can reprogram them to support cancer, according to New York’s Memorial Sloan Kettering Cancer Center. The inflammatory environment, combined with changes in tumour cell metabolism, appears to help the cancer cells withstand stress and multiply.
In addition, the researchers found that in obese individuals the epithelial cells where the tumour originates were actively co-opting other nearby cells to create a more conducive environment for growth. This “cooperation between all cell types” was more pronounced in women with obesity and helped turn early pre-cancerous lesions into invasive disease.
The scale of invasive breast cancer
The study focused specifically on ductal carcinoma in situ (DCIS), a non-invasive precursor to invasive ductal carcinoma (IDC). About half of women diagnosed with DCIS later develop IDC, but there is currently no way to determine which women are most at risk. “As a result, many women with [noninvasive breast cancer] receive the same treatments used for [invasive ductal carcinoma], including surgery, radiation and sometimes hormone therapy,” Hannafon said. “Overtreatment is a major concern, but if we had better ways of determining risk, unnecessary treatments could potentially be reduced.”
Around 321,910 new cases of invasive breast cancer are expected to be diagnosed in the United States this year, according to the American Cancer Society. Most breast cancers are invasive, with invasive ductal carcinoma accounting for 80 per cent of cases and invasive lobular carcinoma making up 10 per cent. In the UK, approximately 59,413 new cases are diagnosed annually, with breast cancer being the fourth most common cause of cancer death and accounting for 7 per cent of all cancer deaths — around 11,200 deaths each year.
Survival rates have improved significantly over the past two decades. In England and Wales, 10-year survival for all stages of breast cancer now exceeds 75 per cent, and five-year survival is nearly 90 per cent. However, survival varies by stage, and the number of women diagnosed with invasive breast cancer has not declined. Obesity is a known risk factor for the disease: in postmenopausal women, being overweight or obese increases breast cancer risk by up to 30 per cent, and Cancer Research UK estimates that 8 per cent of UK breast cancer cases are linked to excess weight.
Obesity is also associated with worse treatment outcomes for most subtypes of breast cancer, including poorer response to adjuvant chemotherapy and a higher risk of distant metastases and death. More than 100 million Americans live with obesity, around 40 per cent of whom are women. In England, 30 per cent of adults are clinically obese, with women slightly more affected than men.
The Oklahoma team now plans to investigate the precise role of Sulfatase 2 in invasive breast cancer, with the hope that the findings could eventually help doctors tailor treatment and reduce the overtreatment of women whose DCIS is unlikely to become invasive.