Anna Batistatou1, Vassiliki Kotoula2, Mattheos Bobos3, George Kouvatseas4, Flora Zagouri5, Eleftheria Tsolaki3, Helen Gogas6, Angelos Koutras7, George Pentheroudakis8, Eleni Timotheadou9, Stavroula Pervana10, Anna Goussia11, Kalliopi Petraki12, Maria Sotiropoulou13, Triantafyllia Koletsa10, Evangelia Razis14, Paris Kosmidis15, Gerasimos Aravantinos16, Christos Papadimitriou5, Dimitrios Pectasides17, George Fountzilas18. 1. Department of Pathology, Ioannina University Hospital, Ioannina, Greece. Electronic address: hecogoff@otenet.gr. 2. Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 3. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. Health Data Specialists Ltd, Athens, Greece. 5. Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 6. First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 7. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece. 8. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. 9. Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece. 10. Department of Pathology, Papageorgiou Hospital, Thessaloniki, Greece. 11. Department of Pathology, Ioannina University Hospital, Ioannina, Greece. 12. Pathology Department, Metropolitan Hospital, Piraeus, Greece. 13. Department of Pathology, Alexandra Hospital, Athens, Greece. 14. Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece. 15. Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece. 16. Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece. 17. Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece. 18. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; Aristotle University of Thessaloniki, Thessaloniki, Greece.
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.
RCT Entities:
BACKGROUND: The prognostic/predictive value of aberrant MYC gene copies and protein expression is not clear in breast cancer. PATIENTS AND METHODS: Early breast cancerpatients 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 cancerpatient 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: Toshiaki Iwase; Kenichi Harano; Hiroko Masuda; Kumiko Kida; Kenneth R Hess; Ying Wang; Luc Dirix; Steven J Van Laere; Anthony Lucci; Savitri Krishnamurthy; Wendy A Woodward; Rachel M Layman; François Bertucci; Naoto T Ueno Journal: BMC Cancer Date: 2020-05-18 Impact factor: 4.430