Originally published as JCO Early Release 10.1200/JCO.2006.09.4482 on April 23 2007
Journal of Clinical Oncology, Vol 25, No 15 (May 20), 2007: pp. 2006-2011
© 2007 American Society of Clinical Oncology.
Efficacy of Letrozole Extended Adjuvant Therapy According to Estrogen Receptor and Progesterone Receptor Status of the Primary Tumor: National Cancer Institute of Canada Clinical Trials Group MA.17
Paul E. Goss,
James N. Ingle,
Silvana Martino,
Nicholas J. Robert,
Hyman B. Muss,
Martine J. Piccart,
Monica Castiglione,
Dongsheng Tu,
Lois E. Shepherd,
Kathleen I. Pritchard,
Robert B. Livingston,
Nancy E. Davidson,
Larry Norton,
Edith A. Perez,
Jeffrey S. Abrams,
David A. Cameron,
Michael J. Palmer,
Joseph L. Pater
From the Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA; Mayo Clinic, Rochester, MN; John Wayne Cancer Institute, Santa Monica, CA; Inova Fairfax Hospital, Falls Church, VA; University of Vermont, Burlington, VT; Institut Jules Bordet, Brussels, Belgium; SIBCSG Coordinating Center, Bern, Switzerland; National Cancer Institute of Canada, Clinical Trials Group, Kingston; Toronto Sunnybrook Regional Cancer Centre, University of Toronto, Toronto, Ontario, Canada; University of Washington, Seattle, WA; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore; Clinical Investigations Branch, National Cancer Institute, Rockville, MD; Memorial Sloan-Kettering Cancer Center, New York, NY; Mayo Clinic, Jacksonville, FL; and the Edinburgh Breast Unit, Western General Hospital, Edinburgh, Scotland
Address reprint requests to Paul E. Goss, MD, PhD, FRCPC, FRCP, Massachusetts General Hospital Cancer Center, 55 Fruit St, Lawrence House, LRH-302, Boston, MA 02114; e-mail: pgoss{at}partners.org
Purpose Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgRthan ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status.
Patients and Methods Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy.
Results The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgRtumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgRsubgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09).
Conclusion These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.
published online ahead of print at www.jco.org on April 23, 2007.
Presented at the 28th annual San Antonio Breast Cancer Symposium, December 8-11, 2005, San Antonio, TX.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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