We present a case of a 60 year-old female treated for metastatic, oestrogen receptor positive breast cancer. She was referred to endocrinology for persistently elevated oestradiol levels raising her oncology team's concern of disease progression. Medications included ribociclib (CDK 4 and 6 inhibitor), goserelin (GNRH agonist) and fulvestrant (oestrogen receptor down regulator). Hormone profile showed oestradiol 530 pmol/L, LH 0.1 IU/L, FSH 6.5 IU/L. Given the discordant picture between sex hormone axis blockade and high levels of oestrogen, repeat testing with liquid chromatography-mass spectrometry (LC-MS) was performed. This showed an expected low oestrogen level at 11 pmol/L.
Oestradiol is synthesised by aromatisation of androgens, catalysed by the enzyme aromatase. In healthy women of reproductive age this primarily occurs in the ovaries. Additionally, oestrogens can be produced peripherally by aromatisation of androgens, adipose tissue being a major site. Oestradiol has conventionally been measured by immunoassays which have only modest sensitivity (lower limits of quantification 100 – 350 pmol/L)1. In oestrogen receptor positive breast cancer a number of drug classes are used to reduce hormone exposure to malignant cells. Fulvestrant competitively binds to oestrogen receptors with consequent downregulation. Fulvestrant is known to interfere with immunoassays giving falsely elevated levels2. This case highlights the need to be mindful of interference when measuring oestradiol and send for LC-MS if clinically warranted.