Extended aromatase inhibitor therapy appears to benefit postmenopausal patients with early-stage, hormone-receptor-positive breast cancer
Adjuvant therapy with an aromatase inhibitor more than 5 years after initial treatment is “safe and beneficial” for postmenopausal patients with hormone-receptor-positive early-stage breast cancer, a study found.
Patients with early-stage hormone-receptor-positive breast cancer may benefit from 10 years of adjuvant treatment with an aromatase inhibitor, according to a new study.
Researchers performed a phase 3, double-blind, placebo-controlled trial in patients treated for early hormone-receptor-positive breast cancer to determine whether extended therapy with an aromatase inhibitor had an effect on disease-free survival. The current standard of care is 5 years of aromatase inhibitor monotherapy up front or after tamoxifen therapy. Study results were published online June 5 by the New England Journal of Medicine.
A total of 1,918 women who had already received 4.5 to 6 years of adjuvant therapy with an aromatase inhibitor, in most cases preceded by tamoxifen, were enrolled in the study. Up to 2 years after completing aromatase inhibitor treatment, patients were randomly assigned to receive 2.5 mg of letrozole or placebo orally once daily for an additional 5 years. Nine hundred fifty-nine patients were assigned to each group. The median age of included patients was 65.1 years. Adherence to the study regimen was 62.5% in the letrozole group and 62.3% in the placebo group.
During a median follow-up of 6.53 years, 67 women in the letrozole group and 98 patients in the placebo group experienced disease recurrence or contralateral breast cancer, and 100 patients in each group died. The 5-year rate of disease-free survival was 95% (95% CI, 93% to 96%) with letrozole and 91% (95% CI, 89% to 93%) with placebo (hazard ratio for recurrence or contralateral disease, 0.66), while the 5-year rate of overall survival was 93% (95% CI, 92% to 95%) and 94% (95% CI, 92% to 95%), respectively (hazard ratio, 0.97). Annual rate of contralateral breast cancer was 0.21% (95% CI, 0.32% to 0.67%) in the letrozole group and 0.49% (95% CI, 0.32% to 0.67%) in the placebo group (hazard ratio, 0.42).
No significant between-group differences in quality of life were noted, but patients in the letrozole group had a higher rate of bone-related adverse effects (i.e., bone pain, bone fractures, and new-onset osteoporosis). Overall, 5.4% of patients in the letrozole group and 3.7% in the placebo group discontinued treatment because of toxic effects of the study drug.
The authors noted that their data on adherence may have limited validity because they relied on patient-self report. However, they concluded that based on their results, adjuvant therapy with an aromatase inhibitor for 5 years after initial treatment is “safe and beneficial” for postmenopausal patients with hormone-receptor-positive early-stage breast cancer. The authors wrote that although hazard ratios for disease progression and contralateral disease were similar with different durations of exposure to tamoxifen and they observed no interaction effects between the study regimen and previous tamoxifen exposure, “it is likely that the benefits of treatment, toxic effects, and quality of life differ among these groups.”
They concluded that the decision about prolonged therapy should be based “largely on the extent of its effect on [the patient] in terms of toxic effects and quality of life, the extent to which bone mineral density is maintained, as indicated by sequential scans, and the patient's individual risk of disease recurrence.”
The authors of an accompanying editorial wrote, “The reduction in contralateral breast cancers and the favorable safety profile seen with letrozole … provide support for the use of aromatase inhibitors for chemoprevention in clinical practice.” They noted that the lack of effect of extended therapy on survival is to be expected because most of the patients in the study were randomly assigned to treatment about 10 years after their initial diagnosis and were past the peak recurrence risk.
“In any event, avoiding a new diagnosis of invasive breast cancer is a benefit in itself,” the editorialists wrote. They noted, however, that clinicians and breast cancer patients should consider the absence of a survival effect as they weigh the risks and benefits of long-term adjuvant therapy.