Postmenopausal Women With Breast Cancer Show Decreased Brain Health, Cognitive Function

Previous studies show that up to 75% of women with breast cancer exhibit disease- and treatment-related affects that include poorer cognitive function in the forms of psychological well-being, decision making, and adherence to treatment.

Results from a recent review published in Frontiers in Aging Neuroscience demonstrate the interconnectedness of brain health, cognitive function, and exercise among postmenopausal women with breast cancer.

At the heart of the authors’ research is epigenomics, or the study of how gene functions are altered but their DNA sequences are not, along with wanting a greater understanding of the neurocognitive changes that women with breast cancer experience and why.

For this reason, they focused on DNA methylation, which modifies gene function, affecting gene expression, and regulates neuronal activation and plasticity.

“Cancer-related changes in cognitive function can be detected across several cognitive domains including difficulties in learning, concentrating, remembering, and decision-making,” the study authors noted. “There is an increasing demand for research devoted to the prevention or amelioration of unwanted late and long-term effects of cancer and its treatment.”

Some important changes, or hallmarks, they highlighted that may be linked to a decline in cognitive function and brain health among postmenopausal women with breast cancer are:

  • Damage to cellular function (eg, telomere attrition, genome instability)
  • Response to the cellular function damage (eg, drops in both mitochondrial function and cellular energies)
  • Alterations to intracellular communications

In addition, the authors believe that a loss of estrogen through cancer treatments can accelerate aging, “resulting in cognitive decline in women with breast cancer.” Here they shined a spotlight on the hippocampus area of the brain, which is inextricably linked to memory.

Because estrogen can augment learning and memory, the authors point out, the hippocampus and its plethora of estrogen receptors support episodic memory. However, women who undergo aromatase inhibitor therapy have demonstrated up to a 98% inhibition in estrogen levels. Chemotherapy can also lead to estrogen deprivation.

Estrogens also are neuroprotective in that they “shield neurons against injury due to oxidative stress, lack of glucose, and certain toxicities and lower the risk of cognitive decline and neurological deficits in women” So, reducing their levels can influence brain aging, the authors pointed out.

As for how exercise relates to brain health and cognitive function among women with breast cancer, the authors’ results were mixed. More evidence is needed, they noted, on exercise’s effectiveness. To make progress in this space, they suggest carefully constructed trials “that optimize the intensity, frequency, and other characteristics of the exercise as it might lead to different patterns on cognitive outcomes.”

A significant limitation on these findings include that cancer biology dictates treatment so that varying degrees of altered cognitive function could be related the different cancer biologies.

For future research, the authors noted the importance of clinical studies that delineate the relationship between cognitive function, brain health, exercise, and DNA methylation in cancer and cancer treatment within the breast cancer space.

“Research in these areas has the potential to increase our understanding of the molecular underpinnings of cancer-related phenotypes such as decreased cognition,” the authors concluded, “and can lead to more targeted treatment and prevention strategies to ameliorate or avoid cognitive decline associated with breast cancer and its treatment.”


Wagner MA, Erickson KI, Bender CM, Conley YP. The influence of physical activity and epigenomics on cognitive function and brain health in breast cancer. Front Aging Neurosci. Published online May 8, 2020. doi:10.3389/fnagi.2020.00123

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