New studies show strikingly fewer breast cancer events with aromatase inhibitors

Confusion in clinical practice grows as
the evidence mounts against using tamoxifen alone

BY EMILY ANDREWS

Patients who switched to anastrozole after two years on tamoxifen had a strikingly lower chance of breast cancer recurrence, concluded an Italian study presented at the San Antonio Breast Cancer Symposium in December. Though the women receiving anastrozole had more gastrointestinal complaints and a higher rate of increased cholesterol levels, there were fewer gynecologic changes such as hot flashes and vaginal dryness.

This follows recent widely publicized findings published in the New England Journal of Medicine in November that in postmenopausal women who have completed five years of tamoxifen therapy, further adjuvant treatment with letrozole significantly reduces risk of cancer recurrence and death. Clinicians will recall that the lead investigator was Dr Paul Goss, director of breast cancer prevention and research at Princess Margaret Hospital in Toronto. On the upside the results were so favourable that the trial was stopped. On the downside, there is now some concern that adequate evaluation of the trade-off between long-term effects and reduced risk of recurrence may not be done.

Yet another trial, which appeared recently in Cancer, has shown an advantage of anastrozole over tamoxifen for postmenopausal patients with early-stage breast cancer, especially those with hormone-positive tumours. Still another ongoing study, this one conducted by the Breast International Group, BIG 1-98, will compare results in four treatment arms: five years of letrozole, five years of tamoxifen, two years of letrozole followed by three of tamoxifen, and two years of tamoxifen followed by three years of letrozole. Results are expected later this year.

Tamoxifen and the aromatase inhibitors work by different mechanisms. Tamoxifen binds to estrogen receptors, inducing both estrogenic and antiestrogenic effects. The aromatase inhibitors inhibit aromatase, a catalyst in estrogen production in peripheral tissues, the main source of estrogen production in postmenopausal women. Until recently, use of aromatase inhibitors in early-stage breast cancer in Canada was limited to those who don't tolerate or had become resistant to tamoxifen.

Together with other emerging evidence on adjuvant therapy with aromatase inhibitors, new evidence has created confusion in clinical practice, said Dr Joseph Ragaz, Head of Oncology at the McGill University Health Centre. "All the studies point in the same direction, but the optimal schedule is not known." Clearly, after five years on tamoxifen women should consider further treatment with an aromatase inhibitor. But for women initiating adjuvant therapy or midway through the five-year course of tamoxifen, the issues of which drug to start on or whether they should switch to an aromatase inhibitor (and if so, when and which one) requires further evidence.