Letrozole appears less detrimental than tamoxifen to cognitive function in breast ca

ORLANDO-Letrozole (Femara) beat out tamoxifen when it came to preserving cognitive function, according to a subanalysis of a major international trial, reported at ASCO 2009. The researchers said that the results were unexpected but nevertheless important for doctors and patients to know as they weigh the pros and cons of anti-estrogen treatment.

Conducted by the International Breast Cancer Study Group, BIG I-98 included postmenopausal women with hormone-receptor-positive early-stage breast cancer, said Karin Ribi, PhD, who is based in the quality of life office at International Breast Cancer Study Group in Bern, Switzerland.

Subjects were randomized to the following adjuvant endocrine treatment:

• Tamoxifen for five years.
• Letrozole for five years.
• Tamoxifen for two years followed by letrozole for three years.
• Letrozole for two years followed by tamoxifen for three years.

During the fifth year of trial treatment, components of objective cognitive function (speed of psychomotor function, visual attention, working and verbal memory, learning) were evaluated in 120 women (mean age 64.2 years) by computerized tests (abstract 510).

Cognitive dysfunction has been recognized as a potential long-term side effect of adjuvant chemotherapy for breast cancer.

The analysis showed that while each of seven cognitive domain scores favored letrozole numerically, only the visual attention score was significantly higher (P = .05) for letrozole. Letrozole, however, was favored significantly (P = .04) in the composite score, the study’s primary endpoint. Also, while impairment below the norm was found in all domains for both drugs, the proportion of impairment for memory was 25.5% for those receiving tamoxifen and only 6.2% with letrozole (P = .003).

“It was expected that because of the estrogen deprivation associated with aromatase inhibitors, patients who received letrozole would have worse cognitive function compared with those who received tamoxifen,” Dr. Ribi said in an interview with Oncology News International. A study limitation was the lack of baseline assessment prior to endocrine therapy, Dr. Ribi noted.

Further results are expected in a year to determine whether this difference persists after women stop taking the medications at the completion of their five years of anti-estrogen treatment. n