Breast Cancer Chemotherapy: Does It Impair Brain Function?

Institution: California School of Professional Psychology
Investigator(s): Mary Wieneke, Ph.D. -
Award Cycle: 1995 (Cycle I) Grant #: 1KB-0071 Award: $307,456
Award Type: New Investigator Awards
Research Priorities
Detection, Prognosis and Treatment>Innovative Treatment Modalities: search for a cure



Initial Award Abstract (1995)
Complaints of impaired mental functioning following chemotherapy ("chemo brain") have long been common among adult cancer patients, but they are poorly documented in the literature; such complaints have most often been attributed to depression or anxiety. Impaired cognitive functioning (thought, concentration, memory) may be an important treatment risk that paradoxically results, in part, from the outcomes of early detection and aggressive treatment. The long-term impact of such phenomena on emotional and psychological functioning, quality of life, and employment should be considered in evaluating the human and economic costs of breast cancer.

This research will expand and more thoroughly address questions raised in a previous single-group study in which significant impairments were found in treated women's functioning for up to one year following completion of chemotherapy. Women who had received chemotherapy for early stage breast cancer showed deficits in several areas of mental functioning despite high-to-normal pre-cancer lQs: attention and concentration; memory, both visual and verbal; mental flexibility and speed of processing; visual function; and motor speed. For the planned research, standard cognitive tests will be used to evaluate brain-behavior relationships in 150 Bay Area women with breast cancer to: 1) assess the long-term effects on brain functioning of conventional chemotherapy and tamoxifen for early stage breast cancer, and 2) identify the contribution of psychological and emotional distress such as depression/anxiety, on mental functioning. Type and amount of chemotherapy, length of treatment, chemotherapy toxicity, and menopausal status will also be assessed for their effects on cognitive functioning. Three groups of women with early stage (I or II) breast cancer who receive: 1) adjuvant chemotherapy (with or without tamoxifen), 2) tamoxifen only, or 3) no chemotherapy, will be compared at three points in time: shortly after diagnosis, and at approximately 1 and 12 months following chemotherapy completion. The value of the proposed research is that techniques to minimize or treat these effects could be developed once the specific cognitive effects are fully documented.


Final Report (1999)
Neuropsychological assessment was used to: (a) assess the long-term effects on brain functioning of conventional chemotherapy and Tamoxifen for early stage breast cancer, and (b) identify the contribution of psychological and emotional distress such as depression/anxiety, on mental functioning. The type and amount of chemotherapy, length of treatment, chemotherapy toxicity, and menopausal status were also assessed for their effects on cognitive functioning.

Subjects were women newly diagnosed with early stage (I or 11) breast cancer who received: (a) adjuvant chemotherapy (with or without Tamoxifen), (b) Tamoxifen only, or (c) no chemotherapy or other drug treatment (control group). Subjects in each of the three conditions were compared at three points in time: (1) shortly after diagnosis, (2) approximately 1 month after chemotherapy completion (~ 6 months), and (3) 1 year after the second testing (~18 months). Of 115 referred patients, 78 met the participation criteria, and 73 completed all three tests and comprise the final sample (chemo, n = 41; tamoxifen-only, n = 16; control, n = 16).

At the baseline measurement, no demographic or cognitive functioning differences were found among women in any of the three treatment groups (the Tamoxifen group was slightly older). All neuropsychological testing results, however, differed significantly from age-, education-, and gender-corrected norms. Psychological measures revealed a range of mild depression in the majority of the women (69%). Anxiety levels were significantly elevated at first testing, with results further suggesting that elevated anxiety levels may affect and impair overall cognitive functioning at this time. This would have implications for decision-making and how newly diagnosed patients take in and process information at this critical time. Differences were not significant between treatment groups over the second and third testings, although all groups improved significantly over time from baseline.

At the second test, all three treatment groups were slightly improved compared to their first test, suggesting a modest practice effect from their test six months earlier. However, there were differences in overall mean cognitive functioning between treatment groups in the amount and rate of change: highest level of functioning and greatest percent change was seen in the control group (7.5%), followed by the tamoxifen group (5.5%), with least improvement and lowest level of cognitive functioning seen in the chemotherapy group ( 1.6%). Affective functioning had also improved in all three groups with a drop in level of both anxiety and depression, although anxiety remained slightly elevated beyond normal range across all three groups.

At the eighteen-month (third) measurement, all three groups still differed significantly from norms (p<.001 in all cases), above in some areas and below in others, even though anxiety/depression levels had fallen close to or within normal range. Anxiety level was still elevated for the chemotherapy group, and least comparative cognitive improvement over time was seen in the chemotherapy group.

Patients' complaints of impaired mental functioning following chemotherapy ("chemo brain") have long been reported among adult cancer patients, but poorly documented in the literature; such complaints have most often been attributed to depression or anxiety. Anxiety may indeed be a factor in cancer patients' cognitive functioning and ability to comprehensively process critical information at time of diagnosis and initial treatment planning. Some areas of cognitive functioning had not returned to "normal" eighteen months after diagnosis; a longer time may be needed to evaluate long term treatment effects of adjuvant chemotherapy and tamoxifen upon cognitive functioning. Impairments in areas such as thinking, concentration, memory, mental flexibility, etc. may be an important treatment risk that paradoxically results, in part, from the improved outcomes of early defection and aggressive treatment.