Findings from a subgroup of the TAILORx trial on early breast cancer reveal that endocrine therapy can contribute to extended cognitive decline, whether or not women receive initial chemotherapy. The results suggest that women taking hormone therapy should be periodically assessed for worsening cognitive symptoms over the course of treatment.

Women taking endocrine therapy for early breast cancer may experience extended cognitive decline whether or not they undergo initial chemotherapy, according to a subgroup analysis of the TAILORx trial (J Clin Oncol 2020;38:1875–86). The findings suggest that chemotherapy produces early but not sustained cognitive impairment. That's why researchers recommend that women taking hormone therapy should be periodically assessed for worsening impairment during treatment.

Launched in 2006, TAILORx randomized 10,273 women with HER2-negative, axillary node-negative early breast cancer, at moderate risk for recurrence, to either chemotherapy followed by endocrine therapy or endocrine therapy alone. In 2010—seeking to isolate the extent to which chemotherapy contributes to cognitive impairment and other adverse effects of therapy—researchers carved out a subset of 579 women who responded to cognitive function questionnaires at baseline and at 3, 6, 12, 24, and 36 months into treatment.

In the subgroup, patients treated with chemoendocrine therapy scored significantly lower on the questionnaire at 3 and 6 months than those receiving endocrine therapy only, but those differences leveled off after 1 year. However, all women showed meaningful cognitive declines for up to 3 years regardless of treatment regimen, compared with their scores before treatment.

“Our results should be reassuring to women taking chemotherapy because cognitive impairment seen early leveled off over time,” says lead investigator Lynne Wagner, PhD, of the Wake Forest School of Medicine in Winston-Salem, NC. “However, it is certainly eye-opening that women on endocrine therapy alone reported declines compared to their pretreatment levels,” she adds. “It tells us we need to be paying more attention to these symptoms.”

The findings validate previous evidence that chemotherapy is not solely responsible for cancer-related cognitive decline—previously known as “chemo brain,” says Carlos H. Barcenas, MD, associate professor of breast medical oncology at The University of Texas MD Anderson Cancer Center in Houston, who was not involved in this study.

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“Cancer-related cognitive decline has several underlying mechanisms that contribute to its etiology, including chemotherapy and endocrine therapy, as well as other medical factors, such as aging, medications, and comorbid conditions,” he explains. “These results should not change current practice to offer chemotherapy to those patients who will benefit from it.”

However, clinicians might consider making treatment modifications for women on hormone therapy who report worsening cognitive symptoms, he says. Patients could be switched to a different aromatase inhibitor or to tamoxifen to see if symptoms improve.

Importantly, Wagner says, these findings should alert physicians to the need for long-term monitoring of women taking endocrine therapy.

“Our results suggest that we need systems in place to periodically capture concerns about cognitive impairment over years, not just at the start of therapy,” she says. “They also underscore the need for additional research to better understand the mechanisms that underlie cognitive changes that occur with hormone therapy and to identify effective interventions.” –Janet Colwell

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©2020 American Association for Cancer Research.
2020
American Association for Cancer Research.