Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients

ABSTRACT

Objective Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment.

Methods Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC–MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment.

Results By use of LC–MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4–162.6), 31.0 (13.4–77.1), 27.2 (7.8–115.8) and 33.3 (20.3–340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC–MS/MS (2.3–182.0 pmol/l) and extraction RIA (2.4–162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05–0.001).

Conclusion Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.

Key words::

• ESTROGENS
• AROMATASE INHIBITORS
• TAMOXIFEN
• POSTMENOPAUSAL WOMEN

ACKNOWLEDGEMENTS

We are grateful to all participating patients and control subjects, without whom it would not have been possible to do this study. We would also like to thank the ARUP Institute for Clinical and Experimental Pathology for supporting this project.

Conflict of interest The authors report no conflict of interest. The authors are responsible for the content and writing of the paper.

Source of funding Funding for this project was provided by the Uppsala–Örebro Regional Research Council, the Swedish Cancer Society, grant No. CAN 2009/ 773, Swedish Research Council, grant No. VR 621-2008–3562, Lions Clubs International, and the Percy Falk Foundation.