Lynne I Wagner1, Robert J Gray2, Joseph A Sparano3, Timothy J Whelan4, Sofia F Garcia5, Betina Yanez5, Amye J Tevaarwerk6, Ruth C Carlos7, Kathy S Albain8, John A Olson9, Matthew P Goetz10, Kathleen I Pritchard11, Daniel F Hayes7, Charles E Geyer12, E Claire Dees13, Worta J McCaskill-Stevens14, Lori M Minasian14, George W Sledge15, David Cella5. 1. Wake Forest School of Medicine, Winston-Salem, NC. 2. ECOG-ACRIN Cancer Research Group Biostatistics Center, Boston, MA. 3. Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. 4. McMaster University, Canadian Cancer Trials Group, Hamilton, Ontario, Canada. 5. Northwestern University School of Medicine, Chicago, IL. 6. University of Wisconsin Madison, Carbone Cancer Center, Madison, WI. 7. The University of Michigan Rogel Cancer Center, Ann Arbor, MI. 8. Loyola University Chicago Stritch School of Medicine, Maywood, IL. 9. University of Maryland School of Medicine, Baltimore, MD. 10. Mayo Clinic, Rochester, MN. 11. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 12. Virginia Commonwealth University Massey Cancer Center Minority/Underserved National Cancer Institute Community Oncology Research Program, Richmond, VA. 13. University of North Carolina, Chapel Hill, NC. 14. National Cancer Institute, Rockville, MD. 15. Stanford University, Stanford, CA.
Abstract
PURPOSE: Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS:Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS:FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E 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 nonsignificant. CONCLUSION:Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.
RCT Entities:
PURPOSE: Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS:Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable 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 FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS: FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E 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 nonsignificant. CONCLUSION: Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.
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