Breast Cancer Therapies Appear to Advance Cognitive Decline

Allison Gandey

July 12, 2007

July 12, 2007 (Chicago) — New data link estrogen deficiency and cognitive decline — a connection that may explain in part why many breast cancer survivors report mental deficits after treatment. Researchers are promoting awareness of the potential dangers of combining endocrine treatments with chemotherapy, which has been poorly studied in the past. The team, reporting at the recent American Society of Clinical Oncology 43rd Annual Meeting, looked at the neuropsychological effects of tamoxifen and exemestane (Aromasin, Pfizer) use after chemotherapy.

The link between cognitive complaints in daily life and adjuvant chemotherapy in breast cancer survivors has been established, lead author Christina Schilder, from the Netherlands Cancer Institute, in Amsterdam, said in her presentation. "The role of endocrine treatments with respect to these cognitive problems is unclear." But, she added, because estrogen deficiency may have adverse effects on certain mental abilities, it is plausible that endocrine treatments affect cognitive functioning in addition to chemotherapy.

The investigators looked at postmenopausal breast cancer patients from the TEAM trial, an open-label, multinational, phase 3 study of more than 4400 patients. The study, conducted by the Cancer Research Campaign Trials Unit, in the United Kingdom, began in 2001. Patients were randomized to receive tamoxifen (20 mg/day) or exemestane (25 mg/day). In the present analysis, patients were also treated with AC chemotherapy — a combination of doxorubicin and cyclophosphamide. The researchers compared the cognitive function of these treated patients with healthy controls.

Cognitive Difficulties Reported After Treatment

Patients underwent neuropsychological testing and were interviewed about any cognitive complaints a year and a half to 4 years after chemotherapy. At the time of testing, all patients were still receiving their assigned endocrine treatment. The researchers measured depression using the Hopkins symptom checklist and fatigue with the multidimensional fatigue inventory. The 48 healthy control subjects underwent the same assessment.

After researchers controlled for age and IQ, both tamoxifen (n = 30) and exemestane (n = 51) users scored significantly lower on information processing speed than healthy controls (reaction times P = .023 and P = .008). Tamoxifen users scored significantly lower on mental flexibility (Stroop card 3; P = .007) and category fluency (P < .0001) than healthy controls.

Both tamoxifen and exemestane users reported significantly more memory problems in daily life compared with healthy controls (27.6% and 25.5% vs 6.3%; P = .02). "These results suggest that endocrine treatments combined with AC chemotherapy have an effect on certain cognitive functions," the researchers presented.

The findings also provide evidence of the distinctive cognitive effects of different types of endocrine therapy. Ms. Schilder and her team add that cognitive complaints did not correlate with test scores but with fatigue and depression.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 566. Presented June 2, 2007.

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