Extended AI Therapy Not Recommended for All HR-Positive Breast Cancers

Extended aromatase inhibition (AI) following sequential endocrine therapy did not significantly improve disease-free survival (DFS) among women with hormone receptor (HR)-positive breast cancer, according to the DATA study. Subgroup analyses indicated, however, that certain high-risk patients may benefit from AI therapy beyond 5 years.

“Some physicians already prescribe extended AI therapy after 5 years of sequential endocrine therapy, in view of the steadily increased risk of disease recurrence in HR-positive breast cancer for years 5–10 by 5%” and by more beyond that, depending on node positivity, wrote study authors led by Vivianne C. G. Tjan-Heijnen, MD, of Maastricht University Medical Centre in the Netherlands. “However, there are currently no data on the importance of extended AI use beyond a total duration of 5 years for patients treated with sequential endocrine therapy, and earlier introduction of AIs might make prolonged treatment beyond 5 years redundant by increasing the chance of cure.”

The DATA study was a prospective, randomized, open-label, phase III trial conducted at 79 hospitals in the Netherlands. A total of 1,912 women were screened, and 1,860 women were eligible, randomized to either 3 or 6 years of anastrozole; all had postmenopausal HR-positive early breast cancer with no signs of recurrence after 2 to 3 years of adjuvant tamoxifen. Results of the analysis were published in Lancet Oncology.

After a median follow-up of 4.2 years, the adapted (beginning beyond 3 years after randomization) DFS rate at 3 years was 90.7% with 6 years of anastrozole, compared with 88.9% with 3 years of anastrozole. At 5 years, these rates were 83.1% and 79.4%, respectively, yielding a hazard ratio of 0.79 (95% CI, 0.62–1.02; P = .066).

A post-hoc subgroup analysis did find that extended therapy benefits some patients. The 5-year adapted DFS rate was 84.4% with 6 years of therapy compared with 76.2% with 3 years of therapy in node-positive patients with estrogen receptor– and progesterone receptor–expressing disease, yielding a hazard ratio of 0.64 (95% CI, 0.46–0.89; P = .0075). Patients with large tumor size (≥ T2) also fared better with extended treatment, with a 5-year adapted DFS rate of 82.7% with 6 years and 69.2% with 3 years of therapy, for a hazard ratio of 0.53 (95% CI, 0.53–0.82; P = .0031).

Though there was no difference between the groups with regard to adverse event rates in the first 3 years of treatment, for the full observation period (0–6 years), there was a higher rate of all-grade arthralgia or myalgia in the 6-year group compared with the 3-year group, at 58% vs 53%. The same was true of osteopenia or osteoporosis (21% vs 16%).

“We cannot recommend the use of extended adjuvant AI after 5 years of sequential endocrine therapy to all postmenopausal women with HR-positive breast cancer,” the authors concluded. “However, our exploratory subgroup analyses suggest that patients with high-risk characteristics might benefit from extended therapy, and that tumors expressing both estrogen and progesterone receptors might drive the benefits we observed.”