“Unparalleled opportunity”
Before TAILORx, it was impossible to quantify the extent to which chemotherapy contributed to cognitive impairment, because all women received chemotherapy, Wagner told Medscape Medical News.
“We had been unable to isolate how much chemotherapy contributed versus all of the other aspects of having cancer, such as surgery, radiation therapy, and endocrine therapy. The design of TAILORx gave us an unparalleled opportunity to uniquely isolate the extent to which chemotherapy contributes to cognitive impairment,” she explained.
TAILORx enrolled 10,273 patients with breast cancer from April 2006 through October 2010. It was amended in January 2010 to include a patient-reported outcome substudy, which assessed cognitive impairment and other symptoms, such as fatigue, endocrine symptoms, and overall health-related quality of life.
All patients had hormone receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative early breast cancer and a midrange 21-gene recurrence score of 11 to 25.
Cognitive impairment was assessed in a subgroup of women using the 37-item Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog) questionnaire, which was administered at baseline and at 3, 6, 12, 24, and 36 months.
The primary endpoint was the score on the 20-item FACT-Cog Perceived Cognitive Impairment (PCI) scale, which is part of the FACT-Cog questionnaire, at 3 months after randomization. The scale scores of the PCI range from 0 to 80, with a higher score indicating better cognitive status.
Of the 734 women who were enrolled in TAILORx after the start of the substudy, 218 women in the group who received chemotherapy plus endocrine therapy and 236 women who received endocrine therapy alone had evaluable FACT-Cog PCI data at baseline and at 3 months.
For both treatment groups, FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months, compared to baseline scores.
However, the pattern of cognitive decline differed between the treatment groups. Among women in the chemotherapy group, impairment was more significant at 3 months (mean PCI score, –3.82; P < .001) and at 6 months (mean PCI score, –2.62; P = .02), compared with the women who received endocrine therapy alone.
PCI scores were comparable in both treatment arms at 12, 24, and 36 months.
“This was not because the women who had chemotherapy improved but because women on endocrine therapy were also reporting a gradual increase in cognitive impairment at 12 months that persisted at 24 and 36 months. So the pace of their cognitive decline was slower and more gradual,” Wagner said.
TAILORx results highlight need for effective interventions
“I was excited to see the publication of this work,” Jamie S. Myers, PhD, RN, of University of Kansas School of Nursing, Kansas City, told Medscape Medical News.
“Drs. Wagner and Cella have been so instrumental in the development of the FACT PROs, and we have used the FACT-Cog PCI subscale in much of our work. The TAILORx study provided a beautiful opportunity to capture PRO data for women with early breast cancer randomized to chemotherapy plus endocrine therapy versus endocrine therapy alone, and I was not surprised that endocrine therapy was associated with reports of cognitive decline,” Myers said in email correspondence.
“This study further confirms the work conducted by my mentor, Dr. Catherine Bender at the University of Pittsburgh. Women receiving endocrine therapy continue to report issues with cognitive function. What was encouraging about this study was confirmation that the contribution of chemotherapy to the cognitive decline that women experience does level out at 12 months for the majority of women. However, as the results clearly demonstrated, neither group in this study returned to baseline by 36 months, likely due to the ongoing impact of the endocrine therapy,” she said.
“I completely agree with the researchers that we must continue to vigilantly monitor and assess women for cognitive changes throughout their treatment trajectory. And these study results certainly highlight the need for effective interventions to either prevent or mitigate the cognitive effects of breast cancer treatment. I hope these researchers will continue to assess women’s report of cognitive function for a significant period of time after endocrine therapy is completed. This would give us very important information about the recovery trajectory for cognitive function once endocrine therapy is complete. I would also hope they would break down the results by category of endocrine therapy, for example, specific aromatase inhibitor versus tamoxifen, as this too could yield important information,” Myers said.
The study was supported by the National Cancer Institute. Wagner, Ganz, Van Dyk, and Myers have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.