From the Journals

‘Eye-opening’: Cognitive decline with endocrine therapy for breast cancer


Cognitive impairment seen in women with early breast cancer who undergo chemotherapy – so-called chemobrain – has now been reported in patients who are treated with endocrine therapy alone.

“The cognitive decline that we observed with endocrine therapy alone was really surprising and very eye-opening, because I think we have generally assumed that hormone therapy is very well tolerated,” lead author Lynne I. Wagner, PhD, professor of social science and health policy at Wake Forest School of Medicine, Winston-Salem, North Carolina, told Medscape Medical News.

“I think this is very important,” she added. “If you have a patient who has been on endocrine therapy for 3 years, don’t just assume that she’s fine and her cognitive function isn’t a concern, because for many women, it is very much a lingering and persistent concern.”

The findings come from a substudy analysis of 218 women who received chemotherapy plus endocrine therapy and 236 women who received endocrine therapy alone.

For most women in the study (58%), endocrine therapy initially consisted of an aromatase inhibitor; 37% of patients received tamoxifen, the researchers report. For chemotherapy, the most common regimens were docetaxel plus cyclophosphamide (70%) and anthracycline-based therapy (20%).

Women who received both chemotherapy and endocrine therapy experienced early and abrupt cognitive decline at 3 and 6 months following treatment; the decline leveled off at 12 and 36 months.

Women who were randomly assigned to receive endocrine therapy alone also experienced loss of cognition, but the loss was more gradual, and, by 36 months, it was the same as occurred in women who had received both chemotherapy and endocrine therapy.

The researchers also found that cognitive function did not return to pretreatment levels, regardless of the treatment the women received.

“We were surprised by the finding that women’s cognitive function did not return to pretreatment levels after finishing chemotherapy, but neither did the group receiving endocrine therapy alone. This highlights the importance of continuing to ask women who are receiving hormonal treatment for breast cancer about their cognitive function, even if they have been on treatment for a few years,” she said.

The findings come from a substudy of the Trial Assigning Individualized Treatment Options (TAILORx) and were published on April 9 in the Journal of Clinical Oncology.

An important contribution

The results of this study make an important contribution toward understanding the potential adverse cognitive effects of chemotherapy in combination with endocrine therapy and endocrine therapy alone, write Patricia A. Ganz, MD, and Kathleen Van Dyk, PhD, of the University of California, Los Angeles, in an accompanying editorial.

However, there was a difference in the effects on cognition with respect to menopausal status, and this should be a covariate or stratification variable, Ganz told Medscape Medical News.

“Clearly, this study shows that endocrine therapy is problematic. Certainly for younger women, the decrement is much worse. It may be that the brain of a young woman who has not yet gone through menopause is ill prepared, if you will, for these hormonal changes, whereas, in older women, even though they may be ill prepared for the toxicity of chemotherapy, endocrine therapy may not be as disruptive, because they have already adjusted to a low-estrogen state,” Ganz said.

“As a clinician, I can say that most of the complaints I hear are from younger women. Older women don’t really complain that much, and this may be because they are at a time in life when they don’t have to multitask, they can sleep late in the morning, and they do not have the same kind of management pressures that a younger woman would have,” she said.

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