Monitoring serum estradiol levels in breast cancer patients during extended adjuvant letrozole treatment after five years of tamoxifen: a prospective trial

• Published in: Breast cancer research and treatment 2021-06, Vol.187 (3), p.769-775
• Main Authors: Faltinová, Mária, Vehmanen, Leena, Lyytinen, Heli, Haanpää, Mikko, Hämäläinen, Esa, Tiitinen, Aila, Blomqvist, Carl, Mattson, Johanna
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adjuvant treatment; Age; Analysis; Aromatase Inhibitors - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Cancer patients; Cancer research; Cancer therapies; Care and treatment; Chemotherapy, Adjuvant; Chromatography, Liquid; Clinical Trial; Clinical trials; Endocrine therapy; Endometrium; Estradiol; Estradiol - therapeutic use; Estrogens; Female; Follicle-stimulating hormone; Humans; Letrozole - therapeutic use; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Menarche; Nitriles - therapeutic use; Oncology; Oncology, Experimental; Phenols; Post-menopause; Postmenopausal women; Prospective Studies; Tamoxifen; Tamoxifen - therapeutic use; Tandem Mass Spectrometry
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06168-w

Purpose To analyze whether monitoring serum estradiol (E2) levels using a highly sensitive and specific liquid chromatography tandem mass spectrometry (LC–MS/MS) method may identify patients with AI failure with E2 levels below the lower limit of quantification (LLOQ) after schwitching from tamoxifen to letrozole. Methods In a prospective study of breast cancer patients switching to letrozole treatment after previous tamoxifen, plasma estrogen levels were measured at baseline and after 3- and 12-months using LC–MS/MS. Results Forty-six patients were classified postmenopausal and entered into the final analysis. Thirty-nine (85%) patients had three- and 12-month E2 concentrations below the LLOQ (5 pmol/L). In the seven patients classified as AI-failures during letrozole treatment, serum E2-MS level rose above 5 pmol/L at 3 months with a mean E2-MS 77.5 pmol/L or 12 months with a mean E2-MS 21 pmol/L. None of the baseline variables i.e., age at diagnosis, age at study entry, age at menarche, BMI, endometrial thickness, total ovarian volume, baseline FSH, E2-IA, or E2-MS were significantly associated with the risk of AI failure in logistic regression. E2 levels at baseline measured by E2-IA did not significantly correlate to the levels measured by E2-MS. Conclusions There is a relatively high risk of inadequate estrogen suppression in patients who switch from tamoxifen treatment to AIs. The use of sensitive and specific assays, such as LC–MS/MS methods, to monitor estrogen levels during AI treatment is essential to minimize the risk of a proceeding inefficient endocrine therapy.