Lynne I. Wagner
Adjuvant chemotherapy plus endocrine therapy appeared to produce early — but not sustained — cognitive impairment compared with endocrine therapy alone for women with early breast cancer, according to patient-reported data from the TAILORx trial published in Journal of Clinical Oncology.
Patients who received adjuvant chemotherapy plus endocrine therapy exhibited significantly greater cancer-related cognitive impairment at 3 months and 6 months relative to those who received endocrine therapy alone. However, investigators observed no significant differences between treatment groups at 12 months or beyond.
The comparable long-term outcomes suggest the term “chemo brain” should no longer be used because it does not accurately describe the cause of cognitive impairment, according to Lynne I. Wagner, PhD, professor of social sciences and health policy at Wake Forest School of Medicine.
“When the medical and research community first began to study cancer-related cognitive impairment, it was assumed that chemotherapy caused lasting impairments in cognitive function — the term ‘chemo brain’ was used for many years to describe this symptom,” Wagner told Healio. “However, research began to emerge demonstrating impairments in cognitive function prior to chemotherapy. This raised questions about the extent to which chemotherapy plays a role in cancer-related cognitive impairment, and the extent to which this symptom is caused or exacerbated by other factors, such as the burden of having a tumor, undergoing surgery and other contributors.”
Wagner and colleagues prospectively studied 454 women with breast cancer and a 21-gene recurrence score of 11 to 25 who were enrolled in TAILORx.
Researchers randomly assigned women to chemotherapy combined with endocrine therapy (n = 218) or endocrine therapy alone (n = 236).
Women in the endocrine therapy and combination therapy groups had similar demographic characteristics, including age (mean, 56 years vs. 55 years) and race (82% white in each).
More than half (58%) received an aromatase inhibitor as initial endocrine therapy and 37% received tamoxifen. Common chemotherapy regimens among women in the combination group included docetaxel plus cyclophosphamide (n = 152; 70%) and anthracycline-based therapy (n = 44; 20%).
“TAILORx allowed us to isolate the unique contribution of chemotherapy to cognitive impairment because women were randomly assigned to chemotherapy or no chemotherapy conditions,” Wagner told Healio.
Researchers evaluated women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire administered at baseline and 3, 6, 12, 24 and 36 months. The primary endpoint was the difference in FACT-Cog Perceived Cognitive Impairment (PCI) score between treatment groups at 3 months.
Researchers defined clinically meaningful changes a priori, and employed linear regression to model PCI scores on baseline PCI, treatment and other factors..
Results showed higher cognitive impairment from baseline to 3 months (linear regression difference in mean PCI, 3.82; P < .001) and from baseline to 6 months (linear regression difference in mean PCI, 2.62; P = .02) among women assigned chemotherapy plus endocrine therapy compared with women assigned endocrine therapy alone.
From baseline to 12 months, 34% of women in the endocrine therapy-only group and 38% of women in the combination group had change scores that exceeded levels considered clinically relevant. Of note, FACT-Cog PCI change scores appeared comparable between treatment groups at 12, 24 and 36 months.
Predictors of health-related quality of life at 12 months included increased PCI, fatigue and endocrine symptoms (P < .001).
Mean PCI change scores from baseline to 3 months among premenopausal women were significantly greater (4.75 points; P = .01), which reflected a greater increase in cognitive impairment among women randomly assigned to chemotherapy plus endocrine therapy vs. endocrine therapy alone.
Postmenopausal women assigned to the combination group reported significantly higher increases in cognitive impairment from baseline to 3, 6, 12 and 24 months compared with women assigned endocrine therapy alone.
“Change in cognitive function is a common, pervasive concern, and there is tremendous value in simply acknowledging that this is a common symptom,” Wagner told Healio. “Clinicians should continually reassess concerns about changes in cognitive function even among women who have been on hormone therapy for 1 year or more. Educating women on what to expect and teaching strategies to compensate for these changes, such as keeping lists and using organizational tools, may help to reduce interference in daily functioning.”
Additional cancer treatment trials conducted through the ECOG-ACRIN Cancer Research Group aim to assess patient-reported cognitive impairment associated with different treatments among various cancer types, according to Wagner.
“My research is also focused on teaching breast cancer survivors strategies to manage fear of cancer recurrence,” Wagner told Healio. “[Although] anxiety is not the cause of cancer-related cognitive impairment, worry and anxiety can exacerbate cognitive problems, and so we are currently examining the extent to which reduced anxiety about recurrence may also be associated with reduced patient-reported cognitive impairments as a secondary outcome.” – by Jennifer Southall
For more information:
Lynne I. Wagner, PhD, can be reached at Wake Forest School of Medicine, Bowman Gray Center for Medical Education, 475 Vine St., Winston-Salem, NC 27101; email: [email protected]
Disclosures: Wagner reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.