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Breast cancer: Aromatase inhibitors take on tamoxifen

Nature Medicine volume 8, pages 1341–1344 (2002)Cite this article

Breast cancer is the most common malignancy in females in most western countries, with about 1 in 10 women at risk of developing the disease in the course of their lifetimes. Since its introduction over 30 years ago, tamoxifen has been the mainstay of the endocrine treatment of breast cancer. It has become the most widely used anticancer drug, and may be thought of as among the first targeted therapies. Yet the results of a major new trial of endocrine therapy after surgery for breast cancer using aromatase inhibitors cast into question tamoxifen's future role.

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Figure 1: Estrogen synthesis and the basic mechanisms of action of tamoxifen and aromatase inhibitors.
Figure 2: Model of the molecular basis of transcriptional activation by estradiol and the partial agonist activity of tamoxifen.

References

  1. Fisher, B. et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J. Natl. Cancer Inst. 90, 1371–1388 (1998).

    Article  CAS  Google Scholar 

  2. Cuzick, J. First results from the International Breast Cancer Intervention Study (IBIS-I): A randomised prevention trial. Lancet 360, 817–824 (2002).

    Article  CAS  Google Scholar 

  3. Buzdar, A & Howell, A. Advances in aromatase inhibition: Clinical efficacy and tolerability in the treatment of breast cancer. Clin. Cancer Res. 7, 2620–2635 (2001).

    CAS  PubMed  Google Scholar 

  4. ATAC Trialists' Group. Anastrozole alone or, in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: First results of the ATAC randomized trial. Lancet 359, 2131–2139 (2002).

  5. Howell, A. & Dowsett, M. Recent advances in the endocrine therapy of breast cancer. Brit. Med. J. 315, 863–866 (1997).

    Article  CAS  Google Scholar 

  6. Kurokawa, H. et al. Inhibition of HER2/neu (erbB2) and mitogen-activated protein kinases enhances tamoxifen action against HER2-overexpressing, tamoxifen-resistant breast cancer cells. Cancer Res. 60, 5887–5894 (2000).

    CAS  PubMed  Google Scholar 

  7. Lee, H. et al. MEKK1 activation of human estrogen receptor α and stimulation of the agonist activity of 4-hydroxytamoxifen in endometrial and ovarian cancer cells. Mol. Endocrinol. 14, 1882–1896 (2000).

    CAS  PubMed  Google Scholar 

  8. Benz, C.C. et al. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res. Treat. 24, 85–95 (1993).

    Article  CAS  Google Scholar 

  9. Ellis, M.J. et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: Evidence from a phase III randomized trial. J. Clin. Oncol. 19, 3808–3816 (2001).

    Article  CAS  Google Scholar 

  10. Zhang, Q.X. et al. An estrogen receptor mutant with strong hormone independent activity from a metastatic breast cancer. Cancer Res. 57, 1244–1249 (1997).

    CAS  PubMed  Google Scholar 

  11. Ali, A. & Coombes, R.C. Endocrine-responsive breast cancer and strategies for combating resistance. Nature Reviews Cancer. 2, 101–112 (2002).

    Article  Google Scholar 

  12. Nicholson, R.I. et al. Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer. Endocr. Relat. Cancer. 8, 175–182 (2001).

    Article  CAS  Google Scholar 

  13. Masamura, S. et al. Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J. Clin. Endocrinol. Metab. 80, 2918–2925 (1995).

    CAS  PubMed  Google Scholar 

  14. Chan, M.W.C. et al. Molecular changes associated with the acquisition of estrogen hypersensitivity in MCF-7 breast cancer cells on long-term estrogen deprivation. J. Steroid Biochem. Mol. Biol. 81, 333–341 (2002).

    Article  CAS  Google Scholar 

  15. Fuqua, S.A. et al. A hypersensitive estrogen receptor-α mutation in premalignant breast lesions. Cancer Res. 60, 4026–4029 (2000).

    CAS  PubMed  Google Scholar 

  16. Geisler, J. et al. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J. Clin. Oncol. 20, 751–757 (2002).

    Article  CAS  Google Scholar 

  17. Howell, A. et al. ICI 182,780 (Faslodex). Development of a novel, “pure” anti-estrogen. Cancer 89, 817–825 (2000).

    Article  CAS  Google Scholar 

  18. Heshmati, H.M. et al. Role of low levels of endogenous estrogen in the regulation of bone resorption in late postmenopausal women. J. Bone Miner. Res. 17, 172–178 (2002).

    Article  CAS  Google Scholar 

  19. Harper-Wynne, C. et al. Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: A pilot study for breast cancer prevention. Cancer Epidemiol. Biomarkers Prev. 11, 614–621 (2002).

    CAS  PubMed  Google Scholar 

  20. Bentrem, D.J. & Jordan, V.C. Tamoxifen, raloxifene and the prevention of breast cancer. Minerva Endocrinol. 27, 127–139 (2002).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Academic Department of Biochemistry, Royal Marsden NHS Trust, Fulham Road, London, UK

    Mitch Dowsett

  2. Department of Medical Oncology, Cancer Research UK, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK

    Anthony Howell

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Correspondence to Mitch Dowsett.

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Competing interests

M.D. is a consultant on the advisory boards of Astrogeneca, Novartis, Pharmacia, Eli Lilly and Roche. A.H. is a consultant on the advisory boards of Astrogeneca, Novartis, Pharmacia and Eli Lilly. A.H. is on the data monitoring committee of Roche and Eli Lilly. M.D. and A.H. are members of the ATAC Trial Steering Committee.

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Dowsett, M., Howell, A. Breast cancer: Aromatase inhibitors take on tamoxifen. Nat Med 8, 1341–1344 (2002). https://doi.org/10.1038/nm1202-1341

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