Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer

N Engl J Med. 2021 Jul 29;385(5):395-405. doi: 10.1056/NEJMoa2104162.

Abstract

Background: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear.

Methods: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture.

Results: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84).

Conclusions: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anastrozole / administration & dosage*
  • Anastrozole / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Aromatase Inhibitors / administration & dosage*
  • Aromatase Inhibitors / adverse effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Fractures, Bone / epidemiology
  • Fractures, Bone / etiology
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Postmenopause
  • Prospective Studies
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen / therapeutic use

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Anastrozole

Associated data

  • ClinicalTrials.gov/NCT00295620