TAILORx sheds light on cognitive decline in early-stage breast cancer
medwireNews: An analysis of the TAILORx trial has revealed early, but not sustained, cognitive decline among breast cancer patients treated with adjuvant chemoendocrine therapy relative to endocrine therapy alone.
This acute decline in cognition with combined chemotherapy and endocrine therapy was seen in the first 6 months of treatment, but at 12 months and beyond levels of impairment were comparable with those seen with endocrine therapy alone.
Lynne Wagner (Wake Forest School of Medicine, Winston-Salem, North Carolina, USA) and team explain that “[s]urvivors of breast cancer receiving [endocrine therapy] may risk suboptimal management of long-term adverse effects if endocrine therapy is assumed to have less long-term CRCI [cancer-associated cognitive impairment] relative to [chemoendocrine therapy].”
The trial included 454 women with hormone receptor-positive, HER2-negative, axillary node-negative early breast cancer who underwent cognitive assessment after 3, 6, 12, 24, and 36 months of initiating treatment using the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI) scale.
Indeed, an acute decline in FACT-Cog PCI scores was seen among the 218 patients randomly assigned to receive chemoendocrine therapy compared with the 236 randomly assigned to receive endocrine therapy alone, with average decreases from baseline of 6.40 versus 2.39 points at 3 months and 6.00 versus 3.28 points at 6 months.
A linear regression model also showed that the decline in cognitive impairment from baseline to 3 and 6 months was significantly greater among those receiving chemoendocrine than endocrine therapy, with the reduction in FACT-Cog PCI scores differing by a respective 3.82 and 2.62 points. The researchers note that the difference at 3 months was “clinically meaningful” exceeding the predetermined threshold of 3.75 points.
However, from 12–36 months there was no significant difference in the average changes in FACT-Cog PCI scores relative to baseline between the treatment groups, which Wagner and team emphasize was “not due to improvement postchemotherapy in the [chemoendocrine] group but rather due to declining scores among women receiving [endocrine therapy].”
They comment: “Given the signiﬁcant proportion of women with breast cancer who may beneﬁt from chemotherapy, it is reassuring for patients and clinicians that the trajectory of cognitive impairment among women randomly assigned to [chemoendocrine therapy] converges with those receiving [endocrine therapy].”
The majority (70%) of women given chemotherapy received docetaxel and cyclophosphamide, which the researchers emphasize is “generally better tolerated” than other regimens, including anthracycline with or without a taxane. The most commonly used endocrine therapies were aromatase inhibitors and tamoxifen.
The researchers note that neither menopausal status nor age significantly influenced the level of cognitive impairment reported, which the researchers say “challenges” previous suggestions that chemotherapy-induced menopause may be “a possible explanation for CRCI.”
Writing in the Journal of Clinical Oncology, Wagner and team conclude: “Both [chemoendocrine] and [endocrine therapy] were associated with lingering impairment, underscoring the need for ongoing attention to CRCI, which appears to stabilize at 12 months and beyond.”
They add that the “[l]ong-term CRCI observed among women receiving [endocrine therapy] should alert clinicians to the importance of ongoing symptom monitoring among this large population of cancer survivors who receive ≥ 5 years of treatment.”
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