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Estradiol testing may guide treatment for patients with estrogen receptor-positive breast cancer, but researchers from Rush University Medical Center in Chicago, Illinois, have a cautionary report about relying on that when fulvestrant, an estrogen receptor antagonist, is used with standard steroid immunoassays. They report on a patient who had a falsely elevated estradiol reading that led to unnecessary procedures.
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Their patient underwent a bilateral oophorectomy and was then started on anti-estrogen therapy with letrozole and fulvestrant, as well as zoledronic acid. At the patient’s request, her primary oncologist obtained a serum estradiol level, which was “unexpectedly” high. The finding was puzzling, the authors say, because she had reported menopausal symptoms, such as hot flashes, which were not consistent with the estradiol level obtained. She also had a complete clinical response to treatment, according to symptoms, radiologic findings, and decreasing levels of carcinoma antigen 125.
A pelvic ultrasound revealed a possible small soft tissue density in the left adnexal region—a “concerning” finding suggesting ovarian remnant syndrome, a rare condition in which ovarian tissue remains after oophorectomy.
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After additional imaging and laparoscopy, pathology revealed fibrovascular and adipose tissue, but no ovarian tissue, ruling out ovarian remnant syndrome as the cause of the elevated estradiol.
Endocrinologists suspected that fulvestrant, which has a molecular structure similar to that of estradiol, was reacting with the standard estradiol immunoassay. That theory was confirmed by testing the serum estradiol levels with the more sensitive, specific liquid chromatography-tandem mass spectrometry, which showed that the levels were actually undetectable.
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Fulvestrant has no known agonist effects; it has not previously been reported to elevate estradiol levels or cross-react with estradiol immunoassays, the authors say. Neither the package insert for fulvestrant nor the product insert for the immunoassay warn about the interaction. The authors, therefore, advise clinicians to be aware of the “high likelihood” of this potential drug-assay interaction.
Source:
Berger D, Waheed S, Fattout Y, Kazlauskaite LU. Clin Breast Cancer. 2016;16(1)e11-e16.
doi: 10.1016/j.clbc.2015.07.004.
