The standard duration of adjuvant tamoxifen therapy for patients with estrogen receptor (ER)–positive breast cancer has been 5 years since follow-up of the NSABP B-14 trial (J Natl Cancer Inst 2001; 93:684) showed that longer durations of the ER inhibitor tamoxifen were associated with statistically inferior disease-free survival (DFS) and a trend toward inferior overall survival. Although aromatase inhibitors (AIs) have gained widespread use in postmenopausal patients, tamoxifen continues to be used in sequence with AIs or in those who cannot tolerate AIs, and it remains the adjuvant endocrine therapy of choice for premenopausal women.

In contrast to the NSABP B-14 study findings, a pooled analysis of 17,477 breast cancer patients in the recently published ATLAS trial (JW Oncol Hematol Dec 11 2012) and the aTTom trial by Gray and colleagues (Abstract 5) demonstrates that longer-duration tamoxifen therapy confers benefit.

Patients who received 10 versus 5 years of tamoxifen achieved a 9% reduction in the risk for death (P=0.008) and a 15% reduction in recurrences (P=0.003). No increase in non–breast cancer deaths was observed with longer-duration therapy. Of note, the benefit was not evident for 10 years, reflecting the known carryover effect of tamoxifen. Although an increase in thrombotic events and endometrial carcinoma occurred with longer-duration therapy, the improvements in breast cancer endpoints translated into a net benefit.

Premenopausal women with an elevated risk for recurrence would be considered for longer-duration tamoxifen therapy, but the decision must include consideration of the toxicity of ongoing treatment, effects on fertility and family planning, and the reality of diminishing compliance. Postmenopausal women unable to tolerate AIs would also be candidates for longer durations of tamoxifen.

Source: Journal Watch Oncology and Hematology