Introduction: Fulvestrant, a selective estrogen receptor degrader widely used in hormone receptor-positive breast cancer, can cause significant analytical interference with estradiol immunoassays due to structural similarity with 17β-estradiol. This interference may result in falsely elevated estradiol measurements, potentially leading to diagnostic confusion and inappropriate clinical interventions. We report a case demonstrating this clinically significant analytical interference and emphasize the importance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in hormone monitoring for patients receiving fulvestrant therapy. Case: A 31-year-old female with metastatic hormone receptorpositive breast cancer receiving combination therapy (fulvestrant, letrozole, ribociclib, and goserelin) presented with inappropriately elevated serum estradiol levels of 566 pmol/L (early follicular phase 200–500 pmol/L), measured by chemiluminescence immunoassay. Despite effective gonadotrophin suppression evidenced by low luteinizing hormone (0.2 IU /L) and follicle-stimulating hormone (4.1 IU/L) levels and clinical amenorrhea, the discordant estradiol elevation raised suspicion of assay interference. Confirmatory testing with LC-MS/MS revealed an estradiol concentration of <36 pmol/L, consistent with expected hormonal suppression and confirming immunoassay cross-reactivity with fulvestrant. The case demonstrates significant fulvestrant interference with estradiol immunoassays, resulting in a greater than 15- fold overestimation compared to LC-MS/MS measurement. The clinical presentation was consistent with effective endocrine therapy, supported by suppressed gonadotropin levels, clinical amenorrhea, and stable disease on imaging. LC-MS/MS provided accurate estradiol measurement, avoiding potential diagnostic confusion and unnecessary clinical interventions. Conclusion Clinicians should be aware of potential fulvestrant interference with estradiol immunoassays when interpreting hormone levels in breast cancer patients. Discordant laboratory findings, particularly elevated estradiol despite clinical evidence of effective hormonal suppression, should prompt consideration of LC-MS/MS confirmation. This case underscores the clinical importance of analytical method selection in hormone monitoring and highlights the need for improved laboratory-clinical communication to optimize patient care in oncology practice.
Fulvestrant ; Immunoassay