Fulvestrant May Falsely Increase 17β-Estradiol Levels in Immunoassays: A Case Report of a 57-Year-Old Postmenopausal Patient With Recurrent Estrogen Receptor-Positive Breast Cancer

Abstract

The prognosis for female patients with locoregionally recurrent breast cancer has improved with the concurrent local and systemic treatment under multiple disciplinary teams. Radiotherapy is a valuable local treatment measure for unresectable locoregional recurrent breast cancer; however, reirradiation in previously irradiated areas is still a matter of debate. Antihormonal therapy achieves an overall survival benefit for most of these patients with estrogen receptor-positive (ER+) breast cancer in both adjuvant and metastatic settings. Fulvestrant is an ER antagonist and selective ER downregulator widely used in antihormonal therapy, especially in recurrent postmenopausal ER+ breast cancers. However, fulvestrant closely resembles 17β-estradiol in its molecular structure which may result in false increases in serum 17β-estradiol levels in commercially available immunoassays leading to incorrect medical decisions. Herein, we report a case of a 57-year-old postmenopausal patient with recurrent ER+ breast cancer treated with concurrent fulvestrant and reirradiation. There was a good clinical response, and the combination treatment was well tolerable. During the quarterly follow-up, we monitored a gradual increase of the serum 17β-estradiol level in immunoassays, unexpectedly, because the patient underwent natural menopause 8 years ago. To rule out the suspected fulvestrant cross-reactivity with 17β-estradiol in immunoassay, the patient’s serum 17β-estradiol levels were subsequently tested with the more sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method, which confirmed 17β-estradiol levels at the postmenopausal level. Concomitant fulvestrant with reirradiation seems to be a safe and effective therapy for locoregionally recurrent ER+ breast cancer. However, a falsely increased 17β-estradiol may result from cross-reactivity between 17β-estradiol and its molecular analog compounds, for example, fulvestrant. Therefore, it is important for the clinicians with the knowledge of this interaction to prevent unnecessary erroneous interpretation of results and avoid wrong medical decisions.

Clinical utility of laboratory developed mass spectrometry assays for steroid hormone testing

“…Additionally, a postmenopausal breast cancer patient treated with fulvestrant, an estrogen receptor antagonist, had gradually increasing estradiol concentrations measured by immunoassay. When the same samples were measured by LC-MS/MS, the estradiol concentrations were in the postmenopausal reference interval, as expected [ 32 ]. As can be appreciated, the added specificity available through use of LC-MS/MS mitigates the issues that immunoassays may have with cross-reactivity.…”

A method to detect fulvestrant interference in estradiol in breast cancer patients

“…The chemical structure similarity between estradiol and fulvestrant makes it impossible for the antibodies used in the immunoassays to distinguish among them ( 15 , 16 ). Consequently, an increase in estradiol level due to cross-reaction with fulvestrant is observed ( 12 , 14 ). In our study, we confirmed the interference of fulvestrant in the estradiol measurement by Centaur CP immunoassay and proposed a simple laboratory tool that allows to differentiate false cases from actual ovarian escape.…”

“…1 ) leading to a cross-reactivity in estradiol immunoassays ( 11 ). A few case reports ( 12 , 13 , 14 ) have been published concerning fulvestrant measured as estradiol by the commercial immunoassays and inducing falsely elevated estradiol results. This is a problem for clinicians and laboratory staff and may wrongly impact medical decisions.…”