Correlation of MYC Gene and Protein Status With Breast Cancer Subtypes and Outcome of Patients Treated With Anthracycline-Based Adjuvant Chemotherapy. Pooled Analysis of 2 Hellenic Cooperative Group Phase III Trials.

Abstract

BACKGROUND:

The prognostic/predictive value of aberrant MYC gene copies and protein expression is not clear in breast cancer.

PATIENTS AND METHODS:

Early breast cancer patients were treated with anthracycline-containing chemotherapy within 2 randomized adjuvant trials. MYC gene and centromere-8 status, as well as Myc protein expression were investigated on 1060 paraffin tumors with fluorescence in situ hybridization and immunohistochemistry, respectively.

RESULTS:

MYC amplification was present in 45% and polysomy-8 in 23% of the tumors. Cytoplasmic staining was observed in 60% and nuclear staining in 26% of the tumors, strongly correlating with each other but not with MYC gene status. MYC gene amplification in the absence of polysomy-8 was associated with adverse disease-free survival (DFS) and overall survival (OS), and remained as an independent unfavorable prognostic factor in multivariate analysis (Wald P = .022 for DFS; P = .032 for OS), whereas patients with MYC amplification and polysomy-8, with polysomy-8 only, and with normal MYC without polysomy-8 performed significantly better compared with those with MYC gene amplification only. Nuclear Myc protein expression benefitted patients treated with paclitaxel (interaction P = .052 for DFS; P = .049 for OS). This interaction remained independently significant in multivariate analysis for OS (overall P = .028).

CONCLUSION:

The effect of MYC gene status on breast cancer patient outcome seems to depend on the underlying chromosomal instability and appears unfavorable for tumors with MYC amplification without polysomy. Nuclear Myc protein expression seems predictive for benefit from adjuvant paclitaxel. These data might aid in the interpretation of relevant findings from large clinical trials.

• Authors: Anna Batistatou, Vassiliki Kotoula, Mattheos Bobos, George Kouvatseas, Flora Zagouri, Eleftheria Tsolaki, Helen Gogas, Angelos Koutras, George Pentheroudakis, Eleni Timotheadou, Stavroula Pervana, Anna Goussia, Kalliopi Petraki, Maria Sotiropoulou, Triantafyllia Koletsa, Evangelia Razis, Paris Kosmidis, Gerasimos Aravantinos, Christos Papadimitriou, Dimitrios Pectasides, George Fountzilas
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 18 Issue 1 Pg. 53-62.e3 (02 2018) ISSN: 1938-0666 [Electronic] United States
• PMID: 28870680 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Anthracyclines
• Antibiotics, Antineoplastic
• MYC protein, human
• Proto-Oncogene Proteins c-myc

Topics

• Adult
• Aged
• Anthracyclines (therapeutic use)
• Antibiotics, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast (cytology, pathology)
• Breast Neoplasms (genetics, mortality, pathology, therapy)
• Cell Nucleus (metabolism)
• Chemotherapy, Adjuvant (methods)
• Chromosomal Instability
• Disease-Free Survival
• Female
• Gene Amplification
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Prognosis
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Young Adult