ASCO guideline update changes tamoxifen recommendations

The American Society of Clinical Oncology (ASCO) recently released an updated guideline that increased the recommended length of tamoxifen therapy in women with hormone receptor-positive breast cancer.

Previously, ASCO had recommended that premenopausal women with hormone receptor-positive breast cancer be treated with 5 years of tamoxifen therapy and that postmenopausal women with hormone receptor-positive breast cancer receive at least 5 years of sequential adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor.

To update these guidelines, a committee performed a systematic review of randomized, clinical trials published from January 2009 to June 2013 and of 3 historical trials whose data were already available in the literature. All of the included trials compared 5 years of tamoxifen therapy with 10 years of therapy or with indefinite therapy. Survival, disease recurrence, and adverse events were the outcomes of interest. The updated recommendations were published online May 27 by the Journal of Clinical Oncology.

Five studies were included in the analysis. In the 2 largest, which were also the most recent and had the longest reported follow-up, 10 years of tamoxifen use conferred a breast-cancer survival advantage. Three of the 5 trials showed an improvement in overall mortality, while 2 of the historical studies found higher mortality in the extended tamoxifen arm. Ten years of tamoxifen use was also associated with lower risk for disease recurrence in 2 of the trials overall and in the estrogen-receptor positive subset of another trial, compared with 5 years of use. Among the 3 studies that reported on contralateral breast cancer, 1 found a statistically significant lower risk with extended tamoxifen therapy and 2 showed no statistically significant difference between groups.

On the basis of these data, the ASCO update committee recommended that pre- or perimenopausal women diagnosed with hormone receptor-positive breast cancer should receive 5 years of adjuvant tamoxifen treatment but that after 5 years, additional therapy should be based on menopausal status. Pre- or perimenopausal women or those whose menopausal status is unknown or undetermined should be offered 10 total years of tamoxifen treatment. Postmenopausal women who have received 5 years of adjuvant tamoxifen therapy should be offered the choice of continuing tamoxifen or changing to an aromatase inhibitor, for a total of 10 years of adjuvant endocrine therapy. Both of the updated recommendations are based on high-quality evidence and are considered strong.

The committee noted that the studies analyzed for the guideline update had differing median follow-up lengths and were performed in different decades. In addition, some of the patients in the included studies did not have hormone receptor-positive disease or their hormone receptor status was not known, and few new data were available on adverse events with longer duration of adjuvant tamoxifen, among other limitations.

The committee recommended that future studies examine patients who have taken aromatase inhibitors for more than 5 years, as well as optimal treatment duration for patients who took tamoxifen for less than 5 years. More information on predictors of recurrence risk and on likely benefits of treatment according to tumor stage, biomarkers, and time since diagnosis is also needed, the committee said.