Adjuvant Chemoendocrine Therapy May Be Associated With Cognitive Impairment

Results from a subgroup of the TAILORx trial, published in the Journal of Clinical Oncology, suggested that adjuvant chemoendocrine therapy is associated with significantly greater cancer-related cognitive impairment (CRCI) compared with endocrine therapy alone among women with breast cancer at 3 and 6 months.¹

However, these differences receded over time, with no significant differences observed at 12 months and beyond. According to the researchers, these findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to endocrine therapy, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is suggested to reduce recurrence risk. 

“We were surprised by the finding that women’s cognitive function did not return to pre-treatment levels after finishing chemotherapy, but neither did the group with hormone therapy alone,” lead author Lynne I. Wagner, PhD, a professor of social sciences and health policy at Wake Forest University, said in a press release.²“These results should alert physicians to the importance of continuing to ask women with breast cancer on hormone therapy about whether their cognitive function is a concern, even if they’ve been on treatment for a few years.”

In this subgroup, women with early breast cancer with a 21-gene recurrence score of 11 to 25 enrolled in TAILORx were randomly assigned to chemoendocrine therapy or endocrine therapy alone. Moreover, cognitive impairment was evaluated among 552 women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The questionnaire included the 20-item Perceived Cognitive Impairment (PCI) scale, the study’s primary endpoint.

FACT-Cog PCI scores were found to be significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. Further, the magnitude of PCI change scores was greater for chemoendocrine therapy than endocrine therapy at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were determined to be nonsignificant.

“Finding that long-term cognitive impairments were comparable between groups confirms we can retire the term ‘chemo-brain’ as it does not accurately describe the whole picture,” Wagner said. 

Given the significant proportion of women with breast cancer who may benefit from chemotherapy, the researchers indicated that it is reassuring for both patients and clinicians that the trajectory of cognitive impairment among women assigned to chemoendocrine therapy converges with those receiving endocrine therapy. However, increased impairment from pre- to post-treatment initiation observed in both groups highlights the need for clinical management of CRCI beyond the initiation of therapy, as well as the need for additional research to illuminate mechanisms and establish effective interventions. 

Additionally, the researchers indicated that long-term CRCI shown among women receiving endocrine therapy should alert clinicians to the importance of continuous symptom monitoring among this large population of cancer survivors who receive ≥ 5 years of treatment. Moreover, survivors of breast cancer receiving endocrine therapy may risk suboptimal management of long-term adverse effects if endocrine therapy is assumed to have less long-term CRCI relative to chemoendocrine therapy.

“We were surprised by the finding that women’s cognitive function did not return to pre-treatment levels after finishing chemotherapy, but neither did the group with hormone therapy alone,” said Wagner. “These results should alert physicians to the importance of continuing to ask women with breast cancer on hormone therapy about whether their cognitive function is a concern, even if they’ve been on treatment for a few years.”

“I think we’ve generally assumed that cognitive impairment is due to chemotherapy,” Wagner continued. “Our findings tell us that hormone therapy may also play a role. Future research is needed to understand better how hormone therapy affects cognition in the context of cancer treatment and also how to treat this symptom.”

References:

1. Wagner LI, Gray RJ, Sparano JA, et a. Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results from TAILORx. J Clin Oncol. doi:10.1200/JCO.19.01866.

2. TAILORx dispels chemo-brain notion: women on hormone therapy also report cognitive decline [news release]. Philadelphia. Published April 9, 2020. ecog-acrin.org/news-and-info/press-releases/tailorx-dispels-chemo-brain-notion-as-women-on-hormone-therapy-also-report-cognitive-decline. Accessed April 14, 2020.