In women with early stage breast cancer, Northwestern Medicine investigators found chemoendocrine therapy (chemotherapy plus hormone therapy) was associated with greater cancer-related cognitive impairment at three and six months compared to endocrine therapy alone. Endocrine therapy was also associated with some level of impairment, according to a recent study published in the Journal of Clinical Oncology.
The findings suggest that combination adjuvant therapy produces early but not sustained cancer-related cognitive impairment, also known as “chemo brain,” and underscore the importance of precision-guided care in identifying women who will most likely to benefit from chemotherapy and spare those who will not.
“This is yet another reason not to give chemotherapy to this particular group of women. Generally speaking, we tend to over-treat in the U.S., and this is one of the few examples of where we can do more by doing less,” said David Cella, PhD, the Ralph Seal Paffenbarger Professor and chair of the Department of Medical Social Sciences.
To determine the correlation between treatment and cancer-related cognitive impairment, the investigators assessed longitudinal patient-reported cognitive impairment in women with early stage hormone receptor positive breast cancer who participated in the TAILORx trial. Participants in this trial were randomly assigned to chemoendocrine therapy or endocrine therapy alone.
In the current study, TAILORx participants with a 21-gene recurrence score of 11 to 25 were asked to complete a cognitive impairment questionnaire at the beginning of the study, and again three months, six months, 12 months, 24 months and 36 months later.
The recurrence score provides prognostic information for women with early stage breast cancer to predict chemotherapy benefit. If the score is high, a woman is likely to benefit from chemotherapy treatment. If the score is low, they are more likely to have a low risk of recurrence in the absence of chemotherapy.
Women randomly assigned to chemoendocrine therapy reported significantly more cognitive impairment during chemotherapy at three and six months compared to women who received endocrine therapy alone.
However, at 12, 24, and 36 months, cognitive impairment was similar between groups, suggesting that chemotherapy produces early but not long-lasting cognitive impairment post treatment and that endocrine therapy alone is also associated with some level of impairment, dispelling the notion that “chemobrain” is entirely to blame.
“This also tells us that women on chemoendocrine therapy might have more complaints about cognitive impairment when they’re actively getting treatment, so they may need more support earlier on,” said Sofia Garcia, PhD, associate professor of Medical Social Sciences and of Psychiatry and Behavioral Sciences, who was a co-author of the study.
Garcia is also research director of the Cancer Survivorship Institute at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The study also revealed a notable difference in the rate of decline in cognitive impairment for premenopausal women versus postmenopausal, according to Cella. Specifically, premenopausal women in the chemoendocrine group experienced a dramatic decline in cognitive impairment at three-months versus a more gradual decline seen in the endocrine therapy group.
Overall, the findings support an ongoing societal shift in counseling women with early breast cancer who fall into a ‘middle risk’ group to not receive chemotherapy, according to Cella.
“It can be challenging to convince women that they don’t really need that chemotherapy, particularly if they’re younger, but there’s no reason to think it’s going to help them beyond what endocrine treatment already does,” said Cella, who is also the director of the Center for Patient Center Outcomes and associate director for Prevention and Control Research at the Lurie Cancer Center.
Currently, the investigators are studying the long-term effects of endocrine therapy, such as fatigue, hormonal changes, adherence to medication and patient cost, and determining what are the best ways to help women manage these factors that may push them to stop treatment altogether.
This work was supported by the National Cancer Institute of the National Institutes of Health, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Susan G. Komen Foundation, the Breast Cancer Research Foundation and Genomic Health.