Benefits of longer-term tamoxifen use may take years to appear

The survival benefits of longer-term therapy using tamoxifen may take at least nine years to develop, according to a new study published in the December 1, 2005 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society. A long-term study evaluating two versus five-year treatment with tamoxifen in women aged 50 years or older found it took nine years to demonstrate significant survival benefits of the longer-term treatment, and that improvements in survival were observed only in postmenopausal women younger than 55 years and with estrogen receptor (ER) positive tumors. In these patients prolonging tamoxifen to five years was associated with a 44 percent reduction in the risk of death.

While tamoxifen is the generally accepted as the standard of care for breast cancer after surgery for its demonstrated improvements in survival, the duration of therapy and the length of time to find significant survival improvements remain unclear. Data consistently suggest that longer duration of treatment results in longer disease-free survival. Data conflicts, however, on whether longer treatment results in longer overall survival and whether it takes many years after treatment to see its benefits.

To investigate the effects of duration of treatment and survival, Maurizio Belfiglio, M.D. and Antonio Nicolucci, M.D. of the Department of Clinical Pharmacology and Epidemiology at Consorzio Mario Negri Sud in Italy and colleagues followed 1901 women with early stage breast cancer treated with surgery and either two- or five-year courses of tamoxifen.

With median follow-up of 115 months the investigators found that women with ER positive tumors who took tamoxifen for five years started to show significantly improved overall survival 90 months after enrollment. Further analysis showed that only women between 50 and 55 years showed overall survival improvement.

The study demonstrates, the authors conclude, that "5 years of tamoxifen are superior to 2 years of treatment in reducing total mortality in ER+ patients 55 years and younger." In older patients the previously documented benefit in terms of disease free survival did not translate into a longer overall survival, probably as a consequence of competing causes of death.

Article: "Twelve-Year Mortality Results of a Randomized Trial of 2 Versus 5 Years of Adjuvant Tamoxifen for Postmenopausal Early-Stage Breast Carcinoma Patients (SITAM 01)," Maurizio Belfiglio, Miriam Valentini, Fabio Pellegrini, Giorgia De Berardis, Monica Franciosi, Maria C.E. Rossi, Michele Sacco, and Antonio Nicolucci on behalf of the GIVIO Group; CANCER; Published Online: October 24, 2005 (DOI: 10.1002/cncr.21474); Print Issue Date: December 1, 2005.

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