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Nat Rev Cancer. 2015 May;15(5):261-75. doi: 10.1038/nrc3920.

Mechanisms of aromatase inhibitor resistance.

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Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.
Department of Medical Oncology, Instituto Nacional de Câncer (INCA), Praça da Cruz Vermelha, 23, 20230-130, Rio de Janeiro, Brazil.
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8 St., 20-954, Lublin, Poland.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston 77030, Texas, USA.


Oestrogen receptor-positive (ER(+)) breast cancer is a major cause of cancer death in women. Although aromatase inhibitors suppress the function of ER and reduce the risk of recurrence, therapeutic resistance is common and essentially inevitable in advanced disease. This Review considers both genomic and cell biological explanations as to why ER(+) breast cancer cells persist, progress and cause an incurable, lethal, systemic disease. The design and outcomes of clinical trials are considered with the perspective that resistance mechanisms are heterogeneous, and therefore biomarker and somatic mutation-based stratification and eligibility will be essential for improvements in patient outcomes.

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