Cognitive Ability May Worsen More With Chemotherapy Plus Endocrine Therapy Versus Endocrine Therapy Alone for Breast Cancer


Patients with breast cancer, regardless of their menopausal status, may face worse cognitive ability with chemotherapy and endocrine therapy, although this may return to its pretreatment level after 36 months.

Cognitive ability may be negatively affected by treatment with chemotherapy and endocrine therapy compared with endocrine therapy alone in women with breast cancer irrespective of menopausal status, recent study findings demonstrated.

Dr. Irene Kang, medical director of women’s health breast oncology at City of Hope Orange County in Irvine, California, presented these findings at the 2022 San Antonio Breast Cancer Symposium.

“Cancer-related cognitive impairment seems to persist over time in a significant proportion of patients,” said Kang during the presentation.

In the study, women with hormone receptor positive (HR+), human epidermal growth factor receptor negative (HER2-) breast cancer were enrolled. HR+ breast cancer means the breast cancer cells respond to estrogen or progesterone, two hormones involved in the menstrual cycle. HER2- means the patients had normal levels of the growth factor receptor protein and is more common than HER2+ disease.

To qualify for the study, they also had one to three positive lymph nodes without distant metastasis, or tumors that appeared away from the site of initial diagnosis.

Patients who met these requirements were randomly assigned to either chemotherapy followed by endocrine therapy (274 patients) or endocrine therapy alone (294 patients).

Participants completed an eight-item questionnaire where patients responded about cancer-related cognitive impairment symptoms they may have experienced over the last seven days. These questions assessed cognitive function at the beginning of the study (baseline), six months into treatment, 12 months after starting treatment and after 36 months.

Scores indicating perceived cognitive function concerns were similar between patients who received chemotherapy with endocrine therapy and those who only received endocrine therapy at baseline. In patients assigned endocrine therapy alone, these scores decreased from baseline to 6 months and 12 months but recovered to their initial cognitive function scores at 36 months, according to the abstract.

In contrast, patients assigned chemotherapy and endocrine therapy also had the same decrease in cognitive function at 6 months and 12 months, although scores did not return to baseline at 36 months.

Of note, 42% of premenopausal women assigned chemotherapy followed by endocrine therapy experienced a sustained significant decline in cognitive function as opposed to 28% for endocrine therapy. For postmenopausal women, these declines were 41% and 36%, respectively.

During the presentation, Kang noted that these results differ from the findings of a similar trial, TAILORx, which used a different cognitive function scale. Results from that trial demonstrated that the differences in cancer-related cognitive impairment between chemotherapy followed by endocrine therapy and endocrine therapy alone “vanished” at 12-month follow-up, she said.

“Our study highlights the need for future investigation of cancer-related cognitive impairment in a more diverse population, as well as understanding who will develop cognitive impairment and who will recover,” Kang said during the presentation.

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