Annals of Oncology Advance Access published online on July 23, 2009
Annals of Oncology, doi:10.1093/annonc/mdp326
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A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada—Clinical Trials Group Trial, MA.12)
1 Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Alberta
2 Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario
3 Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario
4 Department of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta
5 Department of Radiation Oncology, Saskatoon Cancer Centre, Saskatoon, Saskatchewan
6 Department of Medical Oncology, London Regional Cancer Program, London, Ontario
7 Department of Surgical Oncology, Hôpital Du Saint-Sacrement, Quebec City, Quebec
8 Department of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario
9 Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
* Correspondence to: Dr V. H. C. Bramwell, Department of Medical Oncology, Tom Baker Cancer Centre, 1331-29th Street North West, Calgary, Alberta T2N 4N2, Canada. Tel: +1-403-521-3707; Fax: +1-403-238-1651; E-mail: vivienbr{at}cancerboard.ab.ca
Background: In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear.
Patients and methods: Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy.
Results: Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices.
Conclusions: Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.
early breast cancer, premenopausal, tamoxifen following chemotherapy
Received for publication March 19, 2009. Revision received May 5, 2009. Accepted for publication May 6, 2009.