Androgen levels during adjuvant endocrine therapy in postmenopausal breast cancer patients

Abstract

Objective To investigate plasma steroid hormone levels in postmenopausal breast cancer patients with and without adjuvant endocrine therapy and in healthy postmenopausal women.

Methods Steroid hormone levels in postmenopausal breast cancer patients treated with aromatase inhibitors (n = 32) were compared with breast cancer patients treated with tamoxifen (n = 34), breast cancer patients without adjuvant endocrine therapy (n = 15), and healthy postmenopausal women (n = 56). Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, total testosterone, dihydrotestosterone, estrone and estradiol were measured using liquid chromatography–tandem mass spectrometry. Sex hormone binding globulin was measured by solid-phase chemiluminescent immunometric assays, and the free androgen index was calculated.

Results Aromatase inhibitor users did not differ in dihydrotestosterone, total testosterone, androstenedione, DHEA, or free androgen index levels from healthy controls or untreated breast cancer patients. The highest total testosterone levels were found in tamoxifen-treated women, who had significantly higher plasma concentrations than both women treated with aromatase inhibitors and breast cancer patients without adjuvant treatment. Concentrations of cortisol and cortisone were significantly greater in aromatase inhibitor users as well as tamoxifen users, in comparison with healthy controls and untreated breast cancer patients. Aromatase inhibitor users had lower estrone and estradiol plasma concentrations than all other groups.

Conclusion Adjuvant treatment with aromatase inhibitors or tamoxifen was associated with increased cortisol and cortisone plasma concentrations as well as decreased estradiol concentrations. Androgen levels were elevated in tamoxifen-treated women but not in aromatase inhibitor users.

Key words::

• BREAST CANCER
• STEROID HORMONES
• LC-MS/MS
• 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 perform this study. We would also like to thank the ARUP Institute for Clinical and Experimental Pathology for supporting this project.

Conflict of interest Inger Sundström-Poromaa occasionally serves on advisory boards or acts as an invited speaker at scientific meetings for MSD, Bayer Healthcare, and Lundbeck A/S. The other 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 2012/603), the Swedish Research Council (grant no. VR 521-2010-3293 and VR 621-2011-4423), Lions Clubs International, and the Percy Falk Foundation.