Extended Endocrine Therapy in Very Young (≤40) Node-Positive HR+ Early Breast Cancer

Extended Endocrine Therapy in Very Young (≤40) Node-Positive HR+ Early Breast Cancer

Very young, node-positive, hormone receptor–positive (HR+) early breast cancer patients represent a uniquely high-risk subgroup, largely driven by persistent ovarian function and aggressive tumor biology. Emerging long-term data suggest that patients who remain premenopausal after completing 5 years of ovarian function suppression (LHRHa)–based endocrine therapy may derive clinically meaningful benefit from extended endocrine treatment.

In this population, extended endocrine therapy was associated with:

Improved invasive breast cancer–free survival (IBCFS) • 5-year IBCFS: 85% vs 78% • Hazard ratio (HR): 0.63, indicating a 37% relative risk reduction Improved distant recurrence–free survival (DRFS) • 5-year DRFS: 91% vs 83% • HR: 0.49, corresponding to a 51% relative reduction in distant relapse

Importantly, these efficacy gains were achieved without a major increase in long-term toxicity. Rates of fractures and cardiovascular events remained low (~1%), reinforcing the favorable therapeutic index of prolonged endocrine therapy in carefully selected young patients.

Clinical Implications

Chronologic age ≤40 years, node-positive disease, and persistent premenopausal status after 5 years identify a subgroup with sustained estrogen-driven recurrence risk. Extended endocrine therapy should be actively discussed in this setting, with shared decision-making that incorporates: Residual recurrence risk Tolerance of prior endocrine therapy Bone health and cardiovascular risk monitoring These data further support a risk-adapted, biologically driven approach to endocrine duration rather than a fixed 5-year strategy in very young patients.

Key References

Pagani O, et al. Long-term outcomes of adjuvant endocrine therapy in premenopausal women with hormone receptor–positive breast cancer. New England Journal of Medicine. 2014;371:107–118. Francis PA, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. New England Journal of Medicine. 2018;379:122–137. Regan MM, et al. Extended follow-up of the SOFT and TEXT trials: recurrence patterns and long-term toxicity. Journal of Clinical Oncology. 2022;40:3697–3708. Burstein HJ, et al. Endocrine therapy for hormone receptor–positive breast cancer: ASCO guideline update. Journal of Clinical Oncology. 2023.