Key clinical point: Cognitive impairment is worse with chemotherapy plus endocrine therapy (ET) than ET alone in patients with early breast cancer; however, the impairment is not likely to persist beyond the first year.

Major finding: Patients receiving chemotherapy plus ET vs. those receiving ET alone had greater cognitive deterioration in FACT-Cog PCI scores at 3 months (difference, −3.82; P less than .001) and 6 months (difference, −2.62; P = .02) relative to baseline. There were no significant differences between the groups at 12 months and beyond.

Study details: Substudy of TAILORx, a randomized controlled trial of chemotherapy plus ET vs. ET alone in early breast cancer. Cognitive impairment was assessed using a 20-item Perceived Cognitive Impairment (FACT-Cog PCI) scale.

Disclosures: The study was supported by the National Cancer Institute, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Susan G. Komen Foundation, and Genomic Health. The authors reported relationships with multiple pharmaceutical companies and/or research organizations.

COMMENTARY

“Various studies have shown cognitive functional decline in breast cancer patients undergoing chemotherapy. Individual characteristics including baseline mood disorders, fatigue, reduced cognitive reserve, compromised performance status, and genetic variations may predict for greater cognitive impairment with chemotherapy. Endocrine therapy has also been associated with adverse cognitive effects, although data is mixed. This study demonstrates the acute cognitive impact with chemotherapy, while patients receiving endocrine therapy alone exhibit gradual decline. Both groups displayed similar cognitive impairment at 12 months and beyond, which is helpful to see that chemotherapy changes wane. This highlights the importance of identifying which patients with ER-positive breast cancer benefit from chemotherapy, and awareness of longer-term cognitive changes with hormonal therapy, as these agents are prescribed for at least five years and longer duration in select cases. Understanding patient risk factors for cognitive dysfunction and anticipated treatment benefits can help optimize breast cancer outcomes and quality of life.”

Erin Roesch, MD

The Cleveland Clinic

References:

Jim HS, Phillips KM, Chait S, et al. Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. J Clin Oncol. 2012; 30(29):3578-3587.

Janelsins MC, Heckler CE, Peppone LJ, et al. Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. J Clin Oncol. 2016; 35(5):506-514.

Small BJ, Rawson KS, Walsh E, et al. Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors. Cancer. 2011; 117(7):1369-1376.

Underwood EA, Jerzak KJ, Lebovic G, et al: Cognitive effects of adjuvant endocrine therapy in older women treated for early-stage breast cancer: A 1-year longitudinal study. Support Care Cancer. 2019; 27(8):3035-3043.