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Ineffective Inhibition of Aromatase: A Cause for AI Resistance?

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Resistance to Aromatase Inhibitors in Breast Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 8))

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Abstract

While treatment with aromatase inhibitors have improved outcome as compared to tamoxifen in advanced as well as in adjuvant breast cancer therapy, similar to what has been recorded with tamoxifen as well as for oophorectomy in premenopausal women, the reduction in risk for a relapse as well as breast cancer death in the adjuvant setting is less than 50 %. Thus, many patients reveal resistance to aromatase inhibitor therapy even in the early setting. As for metastatic disease, endocrine therapy with aromatase inhibitors, like other forms of endocrine treatment and chemotherapy, remains palliative. Looking at plasma estrogen levels as well as total body aromatization, patients treated with third-generation aromatase inhibitors (anastrozole, letrozole and exemestane) all seem to get profound plasma estrogen suppression as well as effective total body aromatase inhibition. As for studies assessing intratumour estrogen levels, they all point in the same direction; so far, there is no evidence indicating lack of tissue estrogen suppression among individual patients. Important, these findings do not exclude the possibility that in some patients intratumour aromatase to some degree may escape inhibition; however, due to rapid equilibrium with the plasma pool, such a phenomenon most likely should have limited effect on intratumoural estrogen levels.

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Abbreviations

AIs:

Aromatase Inhibitors

ER:

Estrogen Receptor

E2:

Estradiol E1, Estrone

E1S:

Estrone Sulfate

HR:

Hazards Ratio

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Authors and Affiliations

  1. Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway

    Per E. Lønning

  2. Department of Oncology, Haukeland University Hospital, Bergen, Norway

    Per E. Lønning

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  1. Academic Laboratory of Medical Genetics, School of Clinical Medicine, Cancer Research UK Cambridge Institute, Statistics and Computational Biology Laboratory & University of Cambridge, Cambridge, United Kingdom

    Alexey Larionov

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Lønning, P.E. (2015). Ineffective Inhibition of Aromatase: A Cause for AI Resistance?. In: Larionov, A. (eds) Resistance to Aromatase Inhibitors in Breast Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-17972-8_5

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