Previous pivotal trials of the use of an aromatase inhibitor given after five years of adjuvant tamoxifen therapy definitively showed that it was beneficial in patients with early-stage breast cancer. In the main trial (National Cancer Institute of Canada Clinical Trials Group MA.17), once the study was unblinded, women were allowed to start letrozole therapy if desired. Researchers from Canada, the United States, and Scotland, evaluated the follow-up results of the women who switched to the aromatase inhibitor treatment from the placebo group of the initial study—representing a considerable lapse of time during which active therapy was provided—compared with those who did not choose to start letrozole therapy.

All of the postmenopausal women in the trial completed five years of adjuvant tamoxifen therapy. Only events (recurrences, toxicity, and death) that happened after unblinding were reported.

A total 1,579 women (median time from completion of 5-yr of tamoxifen treatment, 2.8 yr) elected to begin letrozole treatment and 804 women decided not to continue with the new therapy. Women in the letrozole group tended to be younger and had superior performance status and were more likely to have had node-positive disease and axillary dissection than women in the control group. With those differences considered, women using letrozole obtained better disease-free survival at the median follow-up of 5.3 years (P <.0001).

With regards to adverse events, women who received letrozole reportedly had more new diagnoses of osteoporosis and significantly more clinical fractures (P = .02). Even after a nearly three-year break from active adjuvant therapy, the researchers concluded, disease-free survival can be improved with letrozole treatment in women who were diagnosed with early-stage disease and who completed a five-year course of tamoxifen therapy.

Goss PE, Ingle JN, Pater JL, et al: Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol 2008; 26: 1948-1955.