Extended Endocrine Therapy Improves Survival Outcomes in Premenopausal Breast Cancer Subtypes

Extended endocrine therapy (EET) beyond 5 years remains a key strategy to reduce recurrence in hormone receptor–positive breast cancer, particularly among premenopausal patients who face a sustained risk of late relapse. A recent study with findings published in JAMA Network Open evaluated the impact of EET across breast cancer subtypes in this population, highlighting nuanced, subtype-specific survival benefits.¹

Patient Population and Treatment Patterns

The study included 487 premenopausal patients with a median age of 37 years. Among them, 276 received EET for a median duration of 3.7 years beyond the initial treatment period. Tumor subtypes were distributed as 18% luminal A–like, 61% luminal B–like, and 21% ERBB2-positive disease.¹

These subtype distinctions are clinically relevant, as luminal A tumors are generally lower risk but prone to late recurrence, whereas luminal B and ERBB2-positive subtypes tend to exhibit more aggressive behavior.² Understanding how EET influences outcomes across these groups is critical for optimizing long-term treatment strategies.

Subtype-Specific Survival Outcomes

EET demonstrated varying degrees of benefit across tumor subtypes. For invasive breast cancer–free survival (IBCFS), the propensity score–weighted HR was 0.68 (95% CI, 0.32-1.45) in luminal A–like disease, 0.63 (95% CI, 0.40-1.00) in luminal B–like/ERBB2-negative disease, and 0.62 (95% CI, 0.21-1.87) in ERBB2-positive disease.¹

More pronounced benefits were observed for distant recurrence–free survival (DRFS), particularly in luminal A–like disease, where the HR was 0.25 (95% CI, 0.08-0.75). In luminal B–like/ERBB2-negative and ERBB2-positive subgroups, DRFS HRs were 0.54 (95% CI, 0.32-0.94) and 0.54 (95% CI, 0.12-2.53), respectively.¹ These findings suggest that EET may substantially reduce the risk of distant recurrence, especially in select patient populations.

Addressing Long-Term Recurrence Risk

Hormone receptor–positive breast cancer is associated with a prolonged risk of recurrence that extends well beyond the initial 5 years of therapy. Previous research findings have shown that recurrence risk persists for up to 20 years, particularly among patients with node-positive or higher-grade disease.²

The findings published in JAMA Network Open reinforce the role of EET in mitigating this long-term risk.¹ However, the variability in benefit across subtypes underscores the need for individualized decision-making, as not all patients derive the same magnitude of benefit.

Balancing Efficacy With Toxicity

While EET offers potential survival advantages, it is also associated with increased adverse effects that may impact adherence. Common toxicities include vasomotor symptoms, thromboembolic events, and bone density loss, particularly with prolonged therapy duration.^2,3

In premenopausal patients, endocrine therapy often involves tamoxifen with or without ovarian suppression, which can intensify menopausal symptoms and negatively affect quality of life.³ As a result, clinicians must carefully weigh the benefits of extended therapy against its tolerability.

Implications for Personalized Treatment

The study data highlight the importance of tailoring endocrine therapy duration based on tumor subtype and recurrence risk.¹ Advances in genomic profiling and risk stratification tools may further refine patient selection, enabling clinicians to identify those most likely to benefit from EET while minimizing unnecessary exposure in lower-risk individuals.

Pharmacists play a key role in supporting these efforts by managing adverse effects, promoting adherence, and educating patients about the risks and benefits of extended therapy. As evidence continues to evolve, multidisciplinary collaboration will be essential for optimizing outcomes for premenopausal patients with breast cancer.

REFERENCES

1. Valenza C, Zheng Y, Milano M, et al. Extended endocrine therapy and survival for breast cancer subtypes in premenopausal patients. JAMA Netw Open. 2026;9(5):e2610427. doi:10.1001/jamanetworkopen.2026.10427

2. Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836-1846. doi:10.1056/NEJMoa1701830

3. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423-438. doi:10.1200/JCO.18.01160