Chromosome 17 Centromere Duplication and Responsiveness to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer12

• Published in: Neoplasia (New York, N.Y.) Vol. 16; no. 10; pp. 861 - 867
• Main Authors: Tibau, Ariadna, López-Vilaró, Laura, Pérez-Olabarria, Maitane, Vázquez, Tania, Pons, Cristina, Gich, Ignasi, Alonso, Carmen, Ojeda, Belén, Ramón y Cajal, Teresa, Lerma, Enrique, Barnadas, Agustí, Escuin, Daniel
• Format: Journal Article
• Language: English
• Published: Neoplasia Press 23-10-2014
• ISSN: 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2014.08.012

Human epidermal growth factor receptor 2
(
HER2
) and
topoisomerase II alpha
(
TOP2A
) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of
TOP2A
gene alterations,
HER2
gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer.
HER2
was tested by fluorescence
in situ
hybridization and
TOP2A
and CEP17 by chromogenic
in situ
hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR).
HER2
amplification was present in 24 (17.5%) of the tumors.
TOP2A
amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29,
P
= .026], and analysis of
TOP2A
amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12,
P
= .054).
TOP2A
amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01,
P
= .007).
HER2
amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication,
TOP2A
amplifications, and
HER2
amplifications were not associated with prognosis.