December 03, 2015
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Anthracycline chemotherapy linked to greater cognitive defects in breast cancer survivors

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Anthracycline chemotherapy regimens appeared associated with greater negative effects on cognitive domains and brain network connections than nonathracycline regimens among survivors of breast cancer, according to observational study results published in JAMA Oncology.

Still, both modalities may have nonspecific effects on other cognitive domains and certain patient-reported outcomes, according to the researchers.

Chemotherapy exposure is associated with an increased risk for cancer-related cognitive difficulties. Specifically, clinical studies have shown an association between anthracycline-based regimens and cognitive impairments or brain changes, according to study background.

Thus, Shelli R. Kesler, PhD, associate professor in the department of neuro-oncology at The University of Texas MD Anderson Cancer Center, and Douglas W. Blayney, MD, professor of medicine at Stanford University School of Medicine, sought to compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity among survivors of breast cancer.

Kesler and Blayney retrospectively reviewed data from 62 survivors of primary breast cancer (mean age, 54.7 ± 8.5 years).

All patients received treatment at Stanford University between 2008 and 2014 and had been off of therapy for more than 2 years. Twenty patients received chemotherapy with anthracyclines and 19 patients received nonanthracycline regimens. The other 23 women did not receive any chemotherapy.

The researchers used neuropsychological tests to evaluate cognitive status, as well as resting state functional MRI imaging to measure functional brain connectivity.

Results showed women treated with anthracycline chemotherapy demonstrated significantly lower verbal memory performance, which included immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001), compared with patients treated with nonanthracycline chemotherapy.

Women treated with anthracyclines also experienced lower left precuneus connectivity (F = 7.48; P = .001) than women treated with nonanthracyclines or who did not receive chemotherapy.

Compared with non–chemotherapy-treated women, those treated with anthracyclines or nonanthracyclines experienced greater cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006).

The number of chemotherapy cycles received or the receipt of endocrine therapy did not appear associated with cognitive function.

Kesler and Blayney acknowledged the small sample size and retrospective study design as potential limitations.

“Larger, prospective studies are needed that include pretreatment and posttreatment assessments so that patients’ individual cognitive and neurobiologic trajectories can be evaluated with respect to potential anthracycline-related neurotoxic events,” Kesler and Blayney wrote. “Animal studies could also examine the effects of potential protective agents on chemotherapy-relayed cognitive dysfunction as well as disrupted default mode network connectivity given that this network seems to be preserved across species.”

In an accompanying editorial, Kelly N.H. Nudelman, PhD, Brenna C. McDonald, PsyD, and Andrew J. Saykin, PsyD, all of the department of radiology and imaging sciences at Indiana University School of Medicine in Indianapolis, wrote that these findings may prompt further research in other areas of neurocognitive function for patients with cancer.

“With the movement toward precision medicine, it will be important to investigate genetic predictors of cognitive risk for various regimens,” they wrote. “Similarly, the roles of cognitive aging and neurodegenerative disorders of aging are largely unexplored in cancer imaging and biomarker studies. Different types of chemotherapy may specifically exacerbate neurotoxic processes present in normal aging and/or neurodegenerative disorders of the aging such as Alzheimer’s or Parkinson’s disease.” – by Cameron Kelsall

Disclosure: Kesler and Brayley report no relevant financial disclosures. Nudelman, McDonald and Saykin report no relevant financial disclosures.