MCW Researchers Investigate Cognitive Effects of Breast Cancer Treatment

Thanks to new research and clinical trials, treatment for breast cancer has come a long way, improving survival rates and quality of life. Aromatase inhibitors (AIs) have become a cornerstone in treating hormone receptor-positive breast cancer, especially for postmenopausal women. These drugs work by blocking the production of estrogen, which can fuel the growth of certain types of breast cancer.

While Aromatase inhibitors are effective in reducing the risk of cancer recurrence, recent guidelines extending their use to 10 years raise important questions about their long-term impact. One of the major concerns is how prolonged estrogen deprivation might affect cognitive function.

Often referred to as “chemo brain,” cognitive dysfunction is a well-documented side effect of chemotherapy, but its connection to AI therapy remains unclear. Many breast cancer survivors report difficulties with memory, concentration, and other cognitive functions during and after cancer treatment. However, the full extent of these cognitive challenges, particularly those linked to AIs, has yet to be thoroughly examined.

Given that more than 3.5 million breast cancer survivors in the U.S. are exposed to AIs, understanding their potential cognitive impact is crucial for informing treatment decisions and improving quality of life for patients.

To address these uncertainties, Liliana E. Pezzin, PhD, JD, professor of medicine at the Medical College of Wisconsin (MCW), and Ann B. Nattinger, MD, MPH, Lady Riders Professor of Breast Cancer Research, associate provost for research and professor of medicine at MCW, have secured a $1.4 million grant from the National Institutes of Health (NIH) to continue their groundbreaking study on the cognitive effects of breast cancer treatments.

The project, titled “A Longitudinal Nationally Representative Study of Cognition-Related Effects of Breast Cancer and Its Treatment,” aims to uncover how common therapies like aromatase inhibitors (AIs) impact cognitive function in breast cancer survivors.

Looking into the Long-term Impact of Breast Cancer Treatment

The research intends to track cognitive function of breast cancer survivors treated with AIs over a five-year period. To do this, Dr. Pezzin and colleagues will leverage data from the Health and Retirement Study (HRS), a longitudinal panel study that surveys a representative sample of approximately 20,000 people in America supported by the National Institute on Aging and the Social Security Administration. By comparing their cognitive trajectories to those of women with breast cancer who did not receive AI therapy as well as to non-cancer controls, the researchers hope to identify any adverse effects AIs may have on cognition beyond normal aging.

Additionally, the study will examine how cognitive function evolves before and after cancer treatment, with an expectation that women treated with AIs will experience a steeper cognitive decline than their counterparts. Finally, the research will quantify the tradeoff between overall and disease-free life expectancy and cognitive functioning, offering vital information that can help patients make more informed decisions about their treatment options.

The team uses a novel approach where women serve as their own controls. By tracking cognitive data from before a cancer diagnosis, researchers can compare each patient’s cognitive function over time. This method is key in isolating the effects of AI therapy from other potential influences, such as the natural cognitive decline that comes with aging.

This innovative approach allows for more reliable findings in a field where randomized controlled trials, the gold standard for establishing causality, are difficult to implement.

“Because women serve as their own controls, we have their history and cognitive trajectory prior to even having cancer, which allows us to get a causal effect of AI on cognition,” says Dr. Pezzin.

A Case for Personalizing Breast Cancer Treatment Plans

Breast cancer survivors and their families are often faced with tough decisions about treatments that can extend life but may come with serious side effects. Dr. Pezzin’s research points to the possibility that AIs, which are used to deprive the brain of estrogen and prevent cancer recurrence, may also play a significant role in cognitive decline. This could have an important impact on patient care.

“The study has implications for a more thoughtful approach to prescribing aromatase inhibitors and possibly doing a dose response that varies by the patient’s cognitive reserve upfront.” says Dr. Pezzin.

By tailoring AI therapies to each patient’s cognitive capacity, doctors may be able to minimize cognitive impairment while still effectively treating the cancer.

As the study progresses into its third year, Dr. Pezzin and her team are excited about the potential of their findings to influence both clinical practice and public health policy. By providing concrete evidence about the cognitive risks associated with aromatase inhibitors, this research can help clinicians tailor breast cancer treatments more thoughtfully, balancing the benefits of preventing cancer recurrence with the preservation of cognitive health.

"People need to be informed about the real implications of their treatment, especially because aromatase inhibitors are recommended for five to ten years post-surgery,” says Dr. Pezzin.