Doctors treating pre‑menopausal breast cancer patients with drugs that shut down the ovaries (LHRH agonists) often check blood estradiol levels, but the tests vary a lot and there’s no clear rule on what counts as “incomplete” suppression. While many clinicians do this monitoring, the evidence that it actually improves outcomes is weak, and newer drugs like LHRH antagonists might work better.

To review the current evidence and inform clinical guidance on the implications of incomplete ovarian function suppression (OFS), the utility of serum estradiol (E2) monitoring, and appropriate management strategies in premenopausal women with early breast cancer (eBC) receiving adjuvant luteinizing hormone-releasing hormone agonist (LHRHa)-based therapy for OFS. A universally accepted definition of incomplete OFS is currently lacking. Although biologically it is plausible that incomplete OFS may compromise the efficacy of endocrine therapy, its actual impact on clinical outcomes remains unclear. Currently, the reliability of E2 monitoring is limited by considerable variability in assay methods and reference ranges, raising concerns about its analytical validity. Notably, in a recent international survey of 205 oncologists managing patients with eBC, 43% reported routinely and 27% occasionally assessing E2 levels in premenopausal patients treated with LHRHa, suggesting inconsistent clinical practice. Standard immunoassays were the most frequently used (65%). However, interpretation of E2 values and subsequent management decisions varied widely, highlighting the absence of standardized clinical guidelines. Although not currently supported by high-level evidence, serum E2 monitoring is widely adopted in clinical practice. Prospective studies and evidence-based recommendations are urgently needed. Emerging strategies to overcome incomplete OFS include LHRH antagonists (e.g., degarelix) and oral SERDs.