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- Title
HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials.
- Authors
Gennari, Alessandra; Sormani, Maria Pia; Pronzato, Paolo; Puntoni, Matteo; Colozza, Mariantonietta; Pfeffer, Ulrich; Bruzzi, Paolo
- Abstract
Background: Adjuvant chemotherapy with anthracyclines improves disease-free and overall survival compared with non-anthracycline-based adjuvant chemotherapy regimens in the treatment of early breast cancer. The role of HER2 status as a marker of anthracycline responsiveness has been explored by subset analyses within randomized clinical trials, with inconsistent results. We performed a pooled analysis of the interaction between HER2 status and the efficacy of adjuvant anthracyclines based on the published subset data. Methods: We searched literature databases to identify randomized trials that compared anthracycline-based with non-anthracycline-based adjuvant chemotherapy regimens in the treatment of early breast cancer and reported efficacy data according to HER2 status. Log hazard ratios (HRs) for disease-free and overall survival were pooled across the studies according to HER2 status by inverse variance weighting. A pooled test for treatment by HER2 status interaction was performed by weighted linear meta-regression. All statistical tests were two-sided. Results: Eight studies (with 6564 randomly assigned patients, of whom 5354 had HER2 status information available) were eligible for this analysis. In HER2-positive disease (n = 1536 patients), anthracyclines were superior to non-anthracycline-based regimens in terms of disease-free (pooled HR of relapse = 0.71; 95% confidence interval [Cl] = 0.61 to 0.83; P < .001) and overall (pooled HR of death from any cause = 0.73; 95% CI = 0.62 to 0.85; P < .001) survival. In HER2-negative disease (n = 3818 patients), anthracyclines did not improve disease-free (HR = 1.00; 95% Cl = 0.90 to 1.11; P = .75) or overall (HR = 1.03; 95% CI = 0.92 to 1.16; P = .60) survival. The test for treatment by HER2 status interaction yielded statistically significant results: for disease-free survival, the chi-square statistic for interaction was 13.7 (P < .001), and for overall survival, it was 12.6 (P < .001). Conclusions: The added benefits of adjuvant chemotherapy with anthracyclines appear to be confined to women who have HER2 overexpressed or amplified breast tumors.
- Subjects
BREAST cancer treatment; CANCER chemotherapy; ANTHRACYCLINES; ANTINEOPLASTIC antibiotics; ADJUVANT treatment of cancer
- Publication
JNCI: Journal of the National Cancer Institute, 2008, Vol 100, Issue 1, p14
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djm252