• Mechanisms of resistance to endocrine therapy (tamoxifen/aromatase inhibitors) in Estrogen-positive breast cancer
  • Khashayar Alikarami,1,* Mohammad Amin Dehghani ,2
    1. Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
    2. Student Research Committee of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


  • Introduction: Tumors that express detectable levels of the ESR1 gene indicate the single largest molecular subtype of breast cancer. Ultimately, patients die from ERα+ breast cancer than from either HER2+ disease and/or from triple negative breast cancer (progesterone receptor-negative, ERα-negative, and HER2-negative). Tamoxifen and aromatase inhibitors are the standard treatment options (Endocrine therapies) for estrogen receptor-positive breast cancer patients.
  • Methods: The relevant articles published in English on database of PubMed were searched using main keywords, including ER-positive breast cancer; aromatase inhibitors; tamoxifen;; drug resistance, endocrine therapy .
  • Results: Prevention of ovarian estrogen production reduces the recurrence of hormone-receptor–positive early breast cancer in premenopausal women, but its value when added to tamoxifen is unknown. The first molecularly targeted treatment of breast cancer was targeting the estrogen receptor (ER) with endocrine therapies that remains a mainstay of treatment of all stages of ER-positive disease. Antiestrogens provide significant benefits when used as adjuvants as well as to treat recurrent or metastatic breast cancer. In postmenopausal women only, aromatase inhibitors can greatly reduce oestrogen concentrations, hence avoiding stimulation of ER-positive breast cancer cells. Resistance to endocrine therapy remains the most significant challenge in treatment of ER+ breast tumors.
  • Conclusion: Tamoxifen reduces the available estrogen to cancer cells by competitively inhibiting the binding of estrogen to the estrogen receptors in breast tissues. However, resistance to these agents has become a major clinical obstacle.
  • Keywords: ER-positive breast cancer; aromatase inhibitors; tamoxifen;; drug resistance, endocrine therapy