Benefit of anthracyclines in early breast cancer limited to HER-positive tumors

January 3, 2008

NEW YORK (Reuters Health) - Anthracycline-based adjuvant chemotherapy for early breast cancer improves overall and disease-free survival only in women whose breast tumors overexpress or amplify HER2, results of a meta-analysis indicate.

"Patients with HER2-negative disease ... could be spared unnecessary toxic effects related to the use of this class of agents," the Italian research team suggests in the Journal of the National Cancer Institute for January 2.

In subgroup analyses of several clinical trial cohorts, evidence regarding the benefits of adjuvant anthracycline treatment based on HER2 status have been inconsistent, Dr. Alessandra Gennari, from the National Cancer Research Institute in Genoa, and her associates note.

Dr. Gennari's group identified eight randomized controlled trials comparing chemotherapy regimens with and without anthracyclines (doxorubicin or epirubicin), in which HER2 status had been determined for most patients (total 5354). Overall, 29% had tumors that overexpressed the HER2 protein or had amplification of the HER2 gene.

When used to treat HER2-positive tumors, anthracycline treatment was associated with a significantly reduced risk of relapse (pooled hazard ratio = 0.71, p < .001) and all-cause mortality during follow-up (HR = 0.73, p <.001), compared with non-anthracycline regimens.

No significant benefit was observed in patients with HER2-negative disease.

"The magnitudes of the differential effects of anthracyclines in HER2-positive patients and in HER2-negative patients were remarkably similar across groups of trials," Dr. Gennari's team states, "suggesting that the interaction between anthracycline use and HER2 status is independent of the type of HER2 assay, the proportion of patients assessed for HER2 status, and the type of anthracycline."

However, Dr. Soonmyung Paik and associates at Allegheny General Hospital in Pittsburgh point out in an editorial that molecular heterogeneity within both HER2-positive and HER2-negative tumors affects sensitivity to chemotherapy.

The editorialists, who serve as investigators for the National Surgical Adjuvant Breast and Bowel Project, maintain that "optimization of adjuvant chemotherapy for patients diagnosed with breast cancer will depend on defining the baseline prognosis and chemosensitivity of each subclass of breast cancer beyond those crudely defined by HER2 status alone."