Study Finds No Cognitive Effects From Endocrine Therapy

Kathleen Van Dyk, PhD

Endocrine therapy (ET), commonly used for lengthy periods in the adjuvant treatment of patients with breast cancer, does not have a detrimental effect on cognitive function in survivors of early-stage disease, according to a study from the University of California Los Angeles (UCLA). Because ET is known to interfere with the action of estrogen in the body and brain, and several studies have previously linked cognitive decline to ET, Van Dyk et al undertook the Mind Body Study (MBS) to investigate a possible link between ET and cognitive impairment.

Patients were evaluated at 4 specific points in time: within 3 months of completing their primary cancer treatment but before initiating ET, if indicated; at 6 months; 12 months; and then, via an additional in-person assessment visit, 3 to 6 years following their baseline evaluation. At each visit, patients were given a battery of questions, blood was collected for genetic and inflammatory testing, and a comprehensive neuropsychological test battery was done to evaluate cognitive function in multiple areas.

Figure 1. Mind Body Study Patient Population

UCLA researchers hypothesized that receiving ET would result in diminished neuropsychological performance, citing previous studies that associated cognitive decline with patients’ self-reported symptoms at the 6-month mark. MBS, however, demonstrated no detrimental effects on cognitive function among patients receiving ET (n = 126) versus no ET (n = 63) (Figure 1).

Figure 2. Neurological Test Battery

However, investigators said the results were surprising, partly because endogenous estrogen is believed to be neuroprotective and ET does penetrate the blood—brain barrier. They noted that well-controlled randomized trials have suggested that tamoxifen, but not aromatase inhibitors, leads to adverse cognitive effects. They said MBS may have lacked sufficient nuance to identify groups at risk for cognitive impairment from ET. They added that factors such as chemotherapy treatment require study of how its neurotoxic effects influence ET (Figure 2): “The current study was powered and designed for broader questions than these, when there was scarce evidence in this area. Thus, future nuanced investigations are needed to better rule out or isolate medication effects and to determine whether we are missing vulnerable subgroups.” Attrition among participants was high, and investigators noted that prior studies of the cognitive effects of ET have shown that attrition is higher among cognitively vulnerable populations, which also may have affected results. Among patients who received ET, 74 participated at the 3- to 6-year follow-up versus 28 in the no-ET group. This represented respective declines of 41.2% and 55.6%.

Figure 3. Baseline Characteristics of Study Sample (N = 189)

The authors noted that the sample included pre- and postmenopausal women, which may have obscured cognitive effects of ET because menopausal status is associated with cognitive changes in addition to influencing the type of ET recommended to the patient (Figure 3). Nevertheless, the study was an important step in evaluating the longterm effects of a commonly prescribed treatment for this patient population. “Women are often recommended to stay on [ET] for 5 to 10 years, so risk to cognitive health can be a big concern,” lead author Kathleen Van Dyk, PhD, a neuropsychologist at the Semel Institute of Neuroscience and Human Behavior and the UCLA Jonsson Comprehensive Cancer Center, said in a statement.

“This study provides some big-picture reassurance for the many women who are taking and will be prescribed these medications; there do not appear to be neuropsychological differences when we compared breast cancer survivors taking endocrine therapy with those who were not,” Van Dyk added. 

Van Dyk K, Crespi CM, Bower JE, et al. The cognitive effects of endocrine therapy in survivors of breast cancer: a prospective longitudinal study up to 6 years after treatment [published online November 28, 2018]. Cancer. onlinelibrary.wiley.com/doi/abs/10.1002/ cncr.31858. Accessed December 12, 2018. doi: 10.1002/cncr.31858.