Anthracycline Regimens May Worsen 'Chemobrain' in Breast Cancer Survivors

Shelli Kesler, PhD

Shelli Kesler, PhD

Patients with breast cancer who have received anthracycline-based (ANTHR) chemotherapy may be more likely to experience “chemobrain”—a cancer-related cognitive impairment that can affect memory, attention, and physical function—than those treated with nonanthracycline-based regimens.

In a small study published in JAMA Oncology, researchers used cognitive tests and MRI imaging data from 62 long-term breast cancer survivors to compare the effects of the two regimens on cognitive status and functional brain connectivity. A control group that did not receive chemotherapy was also evaluated._¹

While both chemotherapy regimens demonstrated some negative effects on cognition, women who were treated with ANTHR chemotherapy presented with significantly lower verbal memory performance, including immediate recall (P = .03) and delayed recall (P < .001; effect sizes, 1.2-1.5), as well as lower left precuneus connectivity in the brain (P = .001; effect sizes, 0.6-1.3), which can impair memory, motor strategies, and visual—spatial skills.

“To our knowledge, this represents the first clinical evidence that ANTHR regimens may be more neurotoxic than non-ANTHR regimens,” the authors wrote.

Of the 62 survivors evaluated, 39 had completed chemotherapy treatment for breast cancer more than 6 months prior. The women were an average age of nearly 55 years and had been off their chemotherapy, on average, more than 2 years. Twenty of the women received four to eight cycles of ANTHR-based chemotherapy, and 19 received four to eight cycles of non-ANTHR regimens. The other 23 breast cancer survivors who did not receive chemotherapy for their breast cancer were controls.

Both chemotherapy groups showed decreased executive function and verbal fluency, but the ANTHR cohort had significantly lower verbal memory function, particularly in retention over time.

Women in the comparator group who had not been treated with chemotherapy had a moderately higher executive function ability than the other groups (P = .08).

Chemotherapy, particularly that to treat breast cancer, has often been associated with cognitive decline, leaving patients feeling “foggy.” However, the literature lacks data on whether specific chemotherapy agents are more neurotoxic than others, the authors noted.

Patients in both chemotherapy groups similarly reported elevated cognitive impairment or dysfunction (P = .002) and psychological distress (P = .006) compared with controls.

“Both chemotherapy groups demonstrated lower executive function and increased psychological distress and fatigue compared with the no-chemotherapy group. These results suggest that ANTHRs may be more toxic for brain systems involved in verbal memory, whereas ANTHR and non-ANTHR regimens are associated with similar negative effects on other cognitive-behavioral domains.”

In a corresponding editorial, authors from the Indiana University School of Medicine, Indianapolis, highlighted the findings of the study²:

“While previous studies have linked chemotherapy and cognitive decline, and a few other studies have linked treatment with differences in brain connectivity, there has been very little research comparing cognitive effects of different types and combinations of chemotherapy because most studies have been underpowered to distinguish these effects,” the authors wrote in their editorial.

The researchers concluded that although both chemotherapy regimens have negative impacts on cognition, ANTHR-regimens may have a particular effect on specific cognitive domains. Still, they acknowledged that further testing is necessary to prove associations.

“These results should be considered preliminary given the study limitations of small sample size and retrospective, cross-sectional design,” the investigators note. “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 ANTHR-related neurotoxic effects.”

1. Kesler SR, Blayney DW. Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors [published online December 3, 2015] JAMA Oncol.

2. Nudelman KNH, McDonald BC, Saykin, AJ. Imaging brain networks after cancer and chemotherapy: Advances toward etiology and unanswered questions [published online December 3, 2015]. JAMA Oncol.