Extended Endocrine Therapy Following 5 Years of Adjuvant Luteinizing Hormone-Releasing Hormone Agonist in Premenopausal Patients With Node-Positive, Hormone Receptor-Positive Breast Cancer: A Cohort Study

J Clin Oncol. 2026 Feb 20;44(6):486-496. doi: 10.1200/JCO-25-01660. Epub 2026 Jan 15.

Abstract

Purpose: To evaluate the clinical benefit of extended endocrine therapy (eET) after 5 years of adjuvant treatment with luteinizing hormone-releasing hormone agonists (LHRHa) in premenopausal women with node-positive, hormone receptor-positive early breast cancer (eBC).

Methods: We conducted a cohort study analysis on two prospectively collected data sets (the Young Women's Breast Cancer Study and IEO Breast Cancer Cohort). Eligible patients were diagnosed with eBC at age ≤40 years (between 2005 and 2016), had node-positive, hormone receptor-positive disease, and remained premenopausal after 5 years of adjuvant LHRHa with no evidence of recurrence. The primary end point was invasive breast cancer-free survival (IBCFS), calculated from the sixth year after the initiation of adjuvant endocrine therapy (ET; study baseline), and adjusted through the propensity score (PS) weighting analysis.

Results: A total of 501 patients were included in the analysis: 287 received eET for a median duration of 3.7 years (IQR, 2.3-5.0), including 48% tamoxifen monotherapy and 52% LHRHa plus tamoxifen or aromatase inhibitor. After a median follow-up of 7.3 years from the study baseline, the PS weighted IBCFS rates at 5 years were 85% in the eET group and 78% in the non-eET group (hazard ratio [HR], 0.63 [95% CI, 0.44 to 0.89]; P = .0135). The PS weighted distant recurrence-free survival rates at 5 years were 91% and 83% in the eET and non-eET group, respectively (cause-specific HR, 0.49 [95% CI, 0.31 to 0.79]). In both groups, bone fractures and major cardiovascular events were reported in 1% of patients.

Conclusion: In this cohort study analysis, extending ET in premenopausal patients with node-positive eBC after 5 years of LHRHa treatment was associated with a clinically meaningful reduction in both invasive and distant breast cancer recurrences.

MeSH terms

  • Adult
  • Antineoplastic Agents, Hormonal* / administration & dosage
  • Antineoplastic Agents, Hormonal* / adverse effects
  • Antineoplastic Agents, Hormonal* / therapeutic use
  • Aromatase Inhibitors / administration & dosage
  • Breast Neoplasms* / chemistry
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Gonadotropin-Releasing Hormone* / agonists
  • Humans
  • Premenopause
  • Prospective Studies
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Tamoxifen / administration & dosage

Substances

  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Aromatase Inhibitors