Can Cognitive Dysfunction in Breast Cancer Patients Be Prevented?

DALLAS—Responding to a growing body of research that suggests cognitive dysfunction and asthenia are prevalent side effects of adjuvant chemotherapy for breast cancer, Joyce O’Shaughnessy, MD, of US Oncology is investigating recombinant human erythropoietin as a neuroprotective agent.

One hundred women with early stage breast cancer have been recruited for a randomized trial at US Oncology centers. All are receiving an anthracycline regimen such as doxorubicin/cyclophosphamide (Cytoxan, Neosar) during the 4-month pilot study. Half will also receive epoetin alfa (Procrit, Eprex, Erypo); the other half will receive a placebo.

"Asthenia and cognitive dysfunction may be significant consequences of adjuvant chemotherapy for breast cancer," explained Dr. O’Shaughnessy, director of the cancer prevention program and co-director of the breast cancer research program at Baylor-Charles A. Sammons Cancer Center. The purpose of the study, she said, is to "determine whether Procrit prevents cognitive dysfunction and decreases the fatigue associated with adjuvant chemotherapy." 

Often Goes Undetected

Impaired memory and decreased ability to concentrate appear to be the most significant cognitive effects in breast cancer patients undergoing adjuvant chemotherapy, according to Dr. O’Shaughnessy. Yet cognitive dysfunction often goes undetected, she said, for two reasons.

1. Few physicians evaluate patients for cognitive dysfunction.

2. Depression and menopausal symptoms, both common in breast cancer patients, can also lead to impaired memory and concentration.

Dr. O’Shaughnessy questioned whether asthenia might be a manifestation of cognitive dysfunction. Feeling fatigued even at rest, a hallmark of asthenia, might show "loss of executive control function, which is the ability to process simple ideas into complex goal-oriented behavior," she stated.

Neuroprotective Effects

Dr. O’Shaughnessy cited several published studies that found breast cancer patients had measurable cognitive impairment after adjuvant chemotherapy, as compared to a control group. For example, in one trial reported in the Journal of the National Cancer Institute (90:210-218, 1998), neuropsychological examinations 2 years after completion of adjuvant therapy found impairment in 32% of patients in a high-dose arm, 17% of patients in a standard-dose arm, and 9% of patients in a control arm.

Evidence that epoetin might have neuroprotective effects comes primarily from research with animal models. It has been shown to prevent glutamate-induced neuronal death in vitro and protect against ischemia-induced cell death in vivo.

Taken together, these studies "suggest that this peptide growth factor may have both neuroprotective and cognitive function-enhancing effects," Dr. O’Shaughnessy summarized.