Aromatase inhibitors better than oestrogen receptor blockers in ER+ breast cancer

Richard Heywood, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Estrogen receptor positive (ER+) breast cancer accounts for approximately 78% of total breast cancer diagnoses (1), and thus represent a large burden of cancer. Due to the oestrogen dependent nature of these tumours, they can be treated by oestrogen receptor antagonists such as tamoxifen, or by aromatase inhibitors such as letrozole (aromatase is the enzyme which converts androgens to oestrogens). In the latest issue of Lancet Oncology, Regan et al (2) report the findings of a large clinical trial assessing the efficacy of aromatase inhibitors versus oestrogen receptor antagonists in ER+ breast cancer.

This trial (BIG-1-98) was a large phase 3, randomised double-blinded trial across 27 centres around the world, involving over 8000 patients. There were 4 trial arms; one receiving letrozole alone for 5 years, one receiving tamoxifen alone for 5 years, one receiving 2 years of letrozole followed by 3 years of tamoxifen, and one receiving 2 years of tamoxifen followed by 3 years of letrozole.

After a median follow up of 8.1 years, letrozole monotherapy was significantly better than tamoxifen monotherapy (overall survival at 8 years 85.4% vs. 81.4%). The sequential therapies of letrozole and tamoxifen did not enhance survival against letrozole alone; indeed the tamoxifen followed by letrozole group showed a trend for worse survival which was borderline significant.

This large trial demonstrates the benefits of letrozole over tamoxifen in the treatment of ER+ breast cancer. It is important that oncologists consider these results when deciding on the management of ER+ breast cancer patients.

References: 

1. Anderson WF, Katki HA, Rosenberg PS. Incidence of Breast Cancer in the United States: Current and Future Trends [Internet]. Journal of the National Cancer Institute 2011 Jul; Available from: http://jnci.oxfordjournals.org/content/early/2011/07/12/jnci.djr257.abst…
doi: 10.1093/jnci/djr257

2. Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-1108.
doi 10.1016/S1470-2045(11)70270-4

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