Late Cognitive and Brain Changes After Breast Cancer Therapy

Institution: University of California, Los Angeles
Investigator(s): Helen Rebecca Rausch, M.S., Ph.D. -
Award Cycle: 2003 (Cycle IX) Grant #: 9WB-0106 Award: $250,000
Award Type: STEP Award
Research Priorities
Community Impact of Breast Cancer>Sociocultural, Behavioral, and Psychological Issues: the human side

Initial Award Abstract (2003)
There are 2 million survivors of breast cancer in the US, and many of these patients remain at risk for psychological and medical sequelae of the chemotherapy and/or hormonal therapy used for cancer treatment. Although breast cancer patients who receive chemotherapy as part of their treatment frequently complain of memory and concentration problems, even years after completion of therapy, few studies have systematically investigated these changes. Recent work suggests that increased neurocognitive deficits may occur in women treated with high-dose or standard-dose post-operative chemotherapy for breast cancer. The proposed study will evaluate a priority issue of the CBCRP, behavioral and psychological factors associated with treatment and long-term survival, by addressing the etiology of the long-term cognitive effects of adjuvant therapy.

We suspect that administration of chemotherapy and/or antiestrogen therapy will result in long-term deficits in memory, attention and concentration in significant numbers of breast cancer patients. These treatment-induced changes in thinking processes will likely be due to alteration of specific parts of the brain that regulate these higher functions. Future efforts to prevent or reduce cognitive deficits will require an understanding of the potential causes of these changes in affected patients. Further, alterations in the brain function of breast cancer patients after chemotherapy and/or hormonal therapy may also affect their emotional status and quality of life.

A current IDEA award has allowed enrollment of a significant number of breast cancer patients in a study designed to assess the behavioral affects of adjuvant chemotherapy and hormonal therapy. These patients underwent a comprehensive behavioral battery of tests prior to treatment and now are returning for post-treatment re-evaluations 9 months later. The proposed STEP award will continue post-treatment neurocognitive evaluations of breast cancer patients and controls at about 24 months and assess the relation of post-treatment deficits in memory or concentration to specific changes in brain structure as identified by neuroimaging studies. Additional correlation of findings with blood estrogen and FSH levels and with red blood cell levels will also be done.

This is a unique study designed to assess changes in brain structure and in cognitive functions in patients as evaluated before and 24 months after the administration of chemotherapy, antiestrogens or both treatments for the management of newly diagnosed breast cancer. Many patients now survive breast cancer and live long periods of time after treatment. We hope that better understanding of the nature and underlying causes of neuropsychological alterations after adjuvant medical therapy will lead to better treatment and improved quality of life for patients afflicted by breast cancer.

Final Report (2006)
Breast cancer patients treated with chemotherapy frequently complain of cognitive problems, after but the cognitive effects of chemotherapy have not been well studied. Our laboratory is interested in understanding the nature and dynamic process of cognitive change following adjuvant chemotherapy in breast cancer patients and in identifying factors that affect cognitive change. We used a prospective, longitudinal design to assess the cognitive functions of the same breast cancer patients from baseline (prior to adjuvant therapy) to various periods after adjuvant therapy. This approach allowed each person to act as their own control and reduced the variability in the data. We also collected data from comparison groups, women not treated with chemotherapy followed at the same time. We addressed the potential impact of different treatment parameters, changes in menopausal symptoms, blood hormone levels, mood and fatigue on cognitive change. Potential brain changes that may correlate with cognitive decreases were studied using a brain MRI.

Our laboratory has been following a select group of breast cancer patients for 4 years. These patients were previously evaluated prior to adjuvant chemotherapy and 11 months after treatment had ended. The current project represents a late follow-up of these same patients, 36 months after treatment. In addition to chemotherapy patients, we have been following breast cancer patients treated with only adjuvant anti-estrogen therapy and a group of women who had breast surgery but no adjuvant therapy. A group of healthy groups matched in age to the breast cancer patients has been longitudinally followed over this same time period.

Data collection is complete, with analyses still in process (as of March, 2006). Preliminary analyses suggest that memory complaints that followed adjuvant chemotherapy typically persist for at least 36 months after treatment. Our data also suggest that younger women (<50 yrs of age at chemotherapy) tend to show increased concern for their memory at the 36 months follow-up compared to concerns they reported 11 months after chemotherapy. This late increased concern relates to continued menopausal symptoms, a decrease in attention scores, and a depression factor. The latter may represent a fatigue component.

Cognitive testing indicates a subtle decline over time in attention/concentration in women treated with chemotherapy, with or without hormonal therapy. However, verbal learning decline initially documented in chemotherapy patients at 11 months post-treatment appears largely reversed by three years after chemotherapy.

Our work provides an understanding of the dynamic change in cognition and memory after adjuvant chemotherapy. This information brings attention to the long-term needs of the breast cancer survivor and provides insight into the overall impact on quality of life of current therapeutic regimens.

Symposium Abstract (2005)
Our research focuses on understanding the nature and dynamics of cognitive changes associated with administration of adjuvant chemotherapy and/or hormonal therapy in patients with primary breast cancer. The extent, duration, and underlying etiology of cognitive changes associated with adjuvant medical therapy are not yet well understood. Most studies reported to date have used a cross-sectional retrospective design wherein baseline differences and background diversity among patients are more likely to mask significant interrelationships. Further, the potential impact of factors such as menopausal symptoms, mood, and fatigue on cognition has not been systematically addressed.

We are utilizing a prospective, longitudinal research design to follow breast cancer patients treated with adjuvant medical therapy. With each patient serving as her own control, assessment was initially performed prior to therapy and then at the first follow-up 9 months after chemotherapy or at a comparable time for patients receiving only antiestrogens. Two additional groups were similarly followed, including breast cancer patients who did not receive adjuvant medical therapy and age-matched healthy controls. Assessments included multiple indices of quality of life (SF-36, self-ratings of memory and mood), cognitive testing, blood hormone levels, and menopausal symptoms.

Currently, we are evaluating the duration and stability of patientsí cognitive profiles by re-examining women at 2nd follow-up > 24 months after chemotherapy or at comparable times after hormonal therapy. We hope to determine whether memory changes found at 9 months post-chemotherapy are sustained. In addition, we seek to identify factors that contribute to cognitive changes, such as type of adjuvant therapy, age, menopausal symptoms, mood and/or fatigue. Lastly, we are using magnetic resonance imaging (MRI) of the brain to discover potential structural changes that correlate with cognitive variables.

All patients are invited to undergo brief telephone interviews that include a shortened self-memory rating scale. In addition, patients have an opportunity for repeat cognitive testing in our laboratory, with or without an accompanying MRI. Preliminary findings suggest that one telephone self-rating of memory is a reliable index of memory concerns in chemotherapy patients (telephone- vs. laboratory- ratings, r=.91, p<.008). Thus, an index of memory concerns may be obtained from participants whether or not they return for repeat full laboratory assessments. To date, our research indicates that memory complaints of patients who underwent chemotherapy continue for > 24 months after treatment, with decreases reported from baseline to 9 months post-treatment (p<.03) and from baseline to >24 months post-treatment (p<.03). Laboratory assessments with these patients are ongoing in order to address the relation of continued memory concerns to objective cognitive test scores and to other biologic, psychological and structural factors.

This work aims to enhance our understanding of dynamic changes in cognitive function after adjuvant medical therapy and to identify contributing factors. Hopefully, this information will lead to novel interventions and improved therapeutic regimens to enhance the quality of life of breast cancer patients.