Ch17CEP duplication predicted anthracycline benefit in early breast cancer

A prospective analysis of results of the UK National Epirubicin Adjuvant Trial indicate that chromosome 17 centromere enumeration probe duplication, and not HER2 or TOP2A duplication, was the best predictor of benefit from the addition of anthracyclines in women with early breast cancer.

Researchers examined 1,941 tumors from 2,931 women from the trial (NEAT/BR9601). They analyzed tissue microarrays for HER2 and TOP2A amplification and deletion, HER1-3 and Ki67 expression, and duplication of chromosome 17 centromere enumeration probe (Ch17CEP).

Results for HER2, TOP2A and Ch17CEP were available for 91% of patients. Twenty-one percent of tumors were HER2 amplified, 10% were TOP2A amplified and 11% were TOP2A deleted. Twenty-three percent showed Ch17CEP duplication, and 61% showed high Ki67.

In univariate analysis, HER2 amplification (HR=1.59; 95% CI, 1.32-1.92) and TOP2A deletion (HR=1.52; 95% CI, 1.20-1.92) were prognostic factors for relapse-free survival. HER2 amplification (HR=1.79; 95% CI, 1.47-2.19) and TOP2A deletion (HR=1.62; 95% CI, 1.26-2.08) were also prognostic factors for OS.

There was no association between HER2, HER1-3, TOP2A or Ki67 and anthracycline benefit, according to the researchers.

In multivariate analysis, there was an association between Ch17CEP duplication and improvement in relapse-free survival and anthracyclines for tumors with normal Ch17CEP (HR=0.92; 95% CI, 0.72-1.18) and abnormal Ch17CEP (HR=0.52; 95% CI, 0.34-0.81). There was also an association noted for OS (HR=0.94; 95% CI, 0.72-1.24).

“Validation in a larger meta-analysis is needed to provide confirmatory evidence to support the adoption of this biomarker in routine clinical practice,” the researchers wrote.

Bartlett JMS. Lancet Oncol. 2010;doi:10.1016/S1470-2045(10)70006-1.