Journal of the National Cancer Institute Advance Access originally published online on December 11, 2007
JNCI Journal of the National Cancer Institute 2007 99(24):1845-1853; doi:10.1093/jnci/djm246
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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Extended Adjuvant Therapy With Anastrozole Among Postmenopausal Breast Cancer Patients: Results From the Randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a
On behalf of the Austrian Breast and Colorectal Cancer Study Group
Affiliations of authors: Departments of Surgery (RJ, MG, ER) and Gynecology (EK, CD), Vienna Medical University, Vienna, Austria; Third Medical Department, Paracelsus Medical University, Salzburg, Austria (RG, BM); First Medical Department, Graz Medical University, Graz, Austria (M. Schmid, HS); Department of Surgery, Wiener Neustadt Hospital, Wiener Neustadt, Austria (WK); Department of Surgery, Sisters of Mercy Hospital, Linz, Austria (CT); Department of Surgery, Hanusch Hospital, Vienna, Austria (M. Stierer); Department of Surgery, Oberpullendorf Hospital, Oberpullendorf, Austria (FH); Department of Surgery, Social Medical Center Sozialmedizinisches zentrum Ost, Vienna, Austria (KR)
Correspondence to: Raimund Jakesz, MD, Department of Surgery, Vienna Medical University, Vienna General Hospital, Waehringer Guertel 18–20, Vienna A-1090, Austria (e-mail: raimund.jakesz{at}meduniwien.ac.at).
Background: Clinical trial data have shown that among breast cancer patients who were disease free after 5 years of adjuvant treatment with tamoxifen, further extended treatment with the nonsteroidal aromatase inhibitor letrozole reduces breast cancer recurrence. We examined the efficacy and tolerability of extended adjuvant therapy with another aromatase inhibitor, anastrozole, for 3 years among women who had completed 5 years of adjuvant therapy.
Methods: Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a is an extension of ABCSG Trial 6, in which hormone receptor–positive postmenopausal patients received 5 years of adjuvant tamoxifen, with or without the aromatase inhibitor aminoglutethimide, for the first 2 years of therapy. For ABCSG Trial 6a, patients who were disease free at the end of Trial 6 were randomly assigned to receive either 3 years of anastrozole or no further treatment. Efficacy data were analyzed with the use of a Cox proportional hazards regression model with two-sided P values and Kaplan–Meier curves, and tolerability data were estimated using logistic regression analysis with odds ratios and 95% confidence intervals (CIs).
Results: ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anastrozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, contralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96, P = .031). Anastrozole was well tolerated, and no unexpected adverse events were reported.
Conclusions: These data confirm the benefit of extending adjuvant tamoxifen therapy beyond 5 years with anastrozole compared with no further treatment. Further research is required to define the optimum length of extended adjuvant therapy and to investigate the possibility of tailoring this period to suit different disease types.
| CONTEXT AND CAVEATS Prior knowledge A large clinical trial found that women who received 5 years of the nonsteroidal aromatase inhibitor letrozole after 5 years of adjuvant tamoxifen experienced a 42% reduction in the risk of recurrence compared with women who received placebo. However, early stoppage of that trial precluded assessments of the long-term efficacy and safety of extended adjuvant treatment. Study design Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a was a prospective randomized open-label clinical trial to compare the efficacy and tolerability of extended adjuvant therapy with anastrozole for 3 years with no further treatment among patients who were disease free at the end of ABCSG Trial 6, which found that adjuvant tamoxifen plus the aromatase inhibitor aminoglutethimide was not superior to adjuvant tamoxifen alone in hormone receptor–positive postmenopausal breast cancer patients. Contribution At a median follow-up of more than 5 years, extended adjuvant therapy with 3 years of anastrozole after successful completion of 5 years of tamoxifen reduced the risk of recurrence by 38% compared with no further treatment. Anastrozole was well tolerated, and no unexpected adverse events were reported. Implications The more manageable side effect profile of anastrozole compared with tamoxifen may allow the duration of adjuvant treatment to extend beyond the 5-year period recommended for tamoxifen. Limitations A prerandomization procedure was used to randomly assign all eligible patients in ABCSG Trial 6 (i.e., all those who remained in the trial and disease free) to an arm of Trial 6a to ensure that there would be no gap in treatment between completion of 5 years of primary adjuvant therapy and commencement of the extended study.
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Manuscript received August 28, 2007; revised October 2, 2007; accepted October 30, 2007.
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