Staying Alert to Lingering Cognitive Impairment With Adjuvant Therapy for Early Breast Cancer

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Long-term cancer-related cognitive impairment reported among women with early breast cancer receiving adjuvant endocrine therapy with or without chemotherapy “should alert clinicians to the importance of ongoing symptom monitoring among this large population of cancer survivors who receive at least 5 years of treatment,” advised the authors of a recent study. They found adjuvant chemoendocrine and endocrine therapy alone “were associated with lingering impairment.”1

Although women who received chemoendocrine therapy reported early and abrupt cognitive decline, it leveled off, and at 12 months and beyond, there were no significant differences in cognitive impairment between the two treatment groups. The researchers warned that assuming endocrine therapy alone is associated with less long-term cancer-related cognitive impairment than chemoendocrine therapy “may risk suboptimal management of long-term adverse effects” among those receiving endocrine therapy alone.

These results are from a subgroup of women participating in the TAILORx trial. This study randomly assigned women with early breast cancer and a mid-range 21-gene recurrence score of 11 to 25 to chemotherapy followed by endocrine therapy or endocrine therapy alone.2

The Patient Perspective

The study’s lead author, Lynne I. Wagner, PhD, said in an interview with The ASCO Post that she considered alerting physicians to the importance of ongoing symptom monitoring in patients receiving not only chemoendocrine therapy, but endocrine therapy alone, to be one of the major contributions of the study. “We’ve generally tended to assume that hormone therapy is well tolerated. Although the changes in cognitive impairment we observed are subtle, they are significant from the patient’s perspective,” she noted. In addition, patients receiving endocrine therapy alone may not realize cognitive impairment may manifest later, at 12 or more months, rather than sooner, as with chemoendocrine therapy.

Dr. Wagner is Professor of Social Sciences and Health Policy at Wake Forest School of Medicine and Director of Research and Clinical Integration, Cancer Prevention and Control, at Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, North Carolina. She noted the need for ongoing attention to be addressed by consulting the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). “The NCCN Guidelines provide a nice framework for reassessing symptoms routinely.”

Although “cognitive changes associated with hormone therapy alone certainly were noticeable to the women on the study,” Dr. Wagner stressed the changes did not constitute “major cognitive impairment.” In addition, the results “do not indicate women should not receive hormonal therapy, but rather be in communication with the medical team if they are experiencing cognitive impairment, to learn some strategies for managing it.”

In determining whether a patient is experiencing cognitive impairment, it is also important “to rule out any contributing factors, such as comorbid medical conditions like anemia or thyroid issues, or medications,” Dr. Wagner added. 

DISCLOSURE: Dr. Wagner has an immediate family member who holds stock or other ownership interests in Eli Lilly, Gilead Sciences, and Johnson & Johnson; has served as a consultant or advisor to Celgene; and has been reimbursed for travel, accommodations, or other expenses by Celgene.


1. Wagner LI, Gray RJ, Sparano JA, et al: Patient-reported cognitive impairment among women with early breast cancer randomly assigned to endocrine therapy alone vs chemoendocrine therapy: Results from TAILORx. J Clin Oncol. April 9, 2020 (early release online).

2. Sparano JA, Gray RJ, Makower DF, et al: Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 379:111-121, 2018.

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