Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx

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 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.

Trial registration: ClinicalTrials.gov NCT00310180.

FIG 1.

CONSORT diagram. TAILORx PRO substudy and number of completed FACT-Cog questionnaires submitted, by time point. Sites were instructed to begin administering PROs upon institutional review board approval; some PRO forms were submitted for follow-up assessments from patients with no baseline PRO data. Sites were instructed to administer follow-up PRO assessments even if earlier assessments were missing, thus explaining the higher number of patients with PRO data at 6 months compared to 3 months. (*) Reasons for missing data: patient not given PRO form (n=13), refusal (n=2), other (n=5), unknown (n=5), site did not provide reason (n=39). CT+E, chemotherapy followed by endocrine therapy; E, endocrine therapy alone; PRO, patient-reported outcome.

FIG 2.

Trajectory of Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment change score from baseline among women treated per protocol for pateint-reported outcome substudy sample. (A) Entire patient-reported outcome substudy sample. (B) Premenopausal sample. (C) Postmenopausal sample.

FIG 3.

Trajectory of Functional Assessment of Cancer Therapy-General change scores from baseline for women treated per protocol for the entire patient-reported outcome substudy sample. QOL, quality of life.

FIG 4.

Prevalence of clinically meaningful change in perceived cognitive impairment (FACT-Cog PCI) from baseline to follow-up by treatment arm. The percentage of patients with worsening (Worse), similar (Same), and improving (Better) perceived cognitive impairment, for each treatment arm. A decrease of > 6.4 points from baseline in the PCI is considered worsening, a difference of less than 6.4 in either direction is considered similar, and an increase of > 6.4 is considered improving. The cutoff of 6.4 is 0.5 of the standard deviation of the baseline PCI scores, which has previously been suggested as a threshold to categorize FACT-Cog scores as worse, similar or improved. CT+E, chemotherapy followed by endocrine therapy; E, endocrine therapy alone.

FIG A1.

Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment change score from baseline: intent to treat analysis trajectory. ITT, intent to treat; PP, per protocol.