Metabolic Health May Influence Breast Cancer Outcomes

Danish researchers warn that metabolic screening should be a priority among breast cancer survivors after finding that those with metabolic syndrome are at increased risk for breast cancer recurrence and death.

“Our findings suggest that metabolic health may play a role in shaping breast cancer outcomes,” said the study’s first author Sixten Harborg, MD, from the department of oncology at Aarhus University/Aarhus University Hospital in Denmark and the department of Nutrition at the Harvard T.H. Chan School of Public Health in Massachusetts.

“As precision medicine continues to evolve, incorporating metabolic profiling into clinical care could help identify subgroups of patients who may benefit from more individualized follow-up and supportive interventions,” he told Inside Precision Medicine.

Metabolic syndrome is defined by the American Heart Association as the presence of three abnormal findings among five potentially modifiable risk factors for cardiovascular and chronic disease, namely high blood pressure, high triglycerides, low high-density lipoprotein, high fasting glucose, and central obesity.

Previous studies have shown that women with metabolic syndrome are more likely to develop breast cancer than those without metabolic syndrome. To investigate the association further, Harborg and colleagues carried out a systematic review and meta-analysis of data from 17 observational studies and randomized controlled trials that included 42,135 breast cancer survivors.

Harborg reported at the 2025 European Congress on Obesity in Malaga, Spain, that breast cancer survivors who had metabolic syndrome at the time of their breast cancer diagnosis had a statistically significant 69% higher risk for recurrence and a significant 83% higher risk for breast cancer mortality than breast cancer survivors without metabolic syndrome.

The data, which is also published in the Journal of Internal Medicine, also showed that breast cancer survivors with metabolic syndrome were a significant 57% more likely to experience a breast cancer-related event (recurrence, new cancer, or death) during follow-up than breast cancer survivors without metabolic syndrome.

The researchers pointed out that there are currently no guidelines recommending metabolic screening and interventions for breast cancer survivors.

They said: “Based on our findings and others, we propose that research is warranted into whether breast cancer survivors might benefit from metabolic screening during their treatment course to improve their chances of avoiding a recurrence or death from their malignancy.”

Metabolic screening in these patients could lead to the early detection of, and thus interventions for, comorbid conditions such as hypertension, diabetes, and dyslipidemia, which could potentially improve treatment outcomes.

However, Harborg cautions that although there are several established treatments targeting metabolic syndrome, including lifestyle interventions such as diet, exercise, and weight loss, as well as medications like statins, antihypertensives, and antidiabetic drugs, they have not yet been specifically tested for their ability to reduce the potential negative impact of metabolic syndrome on breast cancer outcomes.

In addition, the researchers noted that limitations with the data meant they were unable to assess the association between metabolic syndrome and breast cancer outcomes by estrogen receptor status. They also could not evaluate the effect of individual components of metabolic syndrome on breast cancer outcomes.

“However, prior research suggests that central obesity and insulin resistance may be particularly influential,” said Harborg. “Currently, there is no clinical evidence to support more targeted metabolic monitoring based on specific components, but future studies should aim to identify which factors are most predictive in order to inform more precise screening strategies in clinical practice. We hope our study helps highlight the importance of further investigating this area.”

The investigators also acknowledge that the precise mechanisms through which metabolic syndrome heightens the risk of breast cancer and its recurrence remain unclear, but are believed to involve chronic inflammation and hormonal imbalances.

They added: “One possible explanation posits that the excessive body fat associated with metabolic syndrome results in increased levels of circulating estrogen, which may stimulate the growth of breast cancer cells. Additionally, adiposity may induce alterations in the tumor microenvironment that facilitate metastasis, or the spread of cancer. Chronic systemic inflammation, a hallmark of metabolic syndrome, may further contribute to tumor progression by promoting cancer cell survival and impairing immune surveillance. Although our study did not investigate the biological underpinnings of the observed associations, it is likely that multiple interacting mechanisms—primarily driven by obesity-induced molecular changes and chronic inflammation—underlie the link between metabolic syndrome and poor breast cancer outcomes.”

Harborg concluded: “While further research is needed, particularly to clarify causality and effective strategies, this study contributes to the growing recognition that metabolic factors could be considered in a more comprehensive approach to breast cancer care.”