C-MYC alterations and association with patient outcome in early-stage HER2-positive breast cancer from the North Central Cancer Treatment Group N9831 adjuvant trastuzumab trial

Edith A. Perez, Robert B. Jenkins, Amylou C. Dueck, Anne E. Wiktor, Patrick P. Bedroske, S. Keith Anderson, Rhett P. Ketterling, William R. Sukov, Kazunori Kanehira, Beiyun Chen, Xochiquetzal J. Geiger, Cathy A. Andorfer, Ann E. McCullough, Nancy E. Davidson, Silvana Martino, George W. Sledge, Peter A. Kaufman, Leila A. Kutteh, Julie R. Gralow, Lyndsay N. HarrisJames N. Ingle, Wilma L. Lingle, Monica M. Reinholz

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Purpose: Findings from the human epidermal growth factor receptor 2 (HER2) -positive National Surgical Adjuvant Breast and Bowel Project (NSABP) B31 trial suggested that MYC/HER2 coamplification (> 5.0 copies/nucleus) was associated with additional benefit from adjuvant trastuzumab in patients with early-stage breast cancer. To further explore this relationship, we investigated associations between MYC amplification and disease-free survival (DFS) in a similar adjuvant trastuzumab HER2-positive breast cancer trial - North Central Cancer Treatment Group (NCCTG) N9831. Patients and Methods: This analysis included 799 patients randomly assigned to receive chemotherapy alone or with concurrent trastuzumab on N9831. Fluorescence in situ hybridization (FISH) was performed by using a dual-probe mixture for MYC and centromere 8 (MYC:CEP8) on tissue microarrays. MYC amplification was prespecified as MYC:CEP8 ratio > 2.2 or average MYC copies/nucleus > 5.0. Exploratory variables included polysomy 8. Results: In comparing DFS (median follow-up, 4.0 years) between treatments, patients with MYC:CEP8 ratio ≤ 2.2 (n = 618; 77%) and > 2.2 (n = 181; 23%) had hazard ratios (HRs) of 0.46 (P < .001) and 0.67 (P = .33), respectively (interaction P = .38). Patients with MYC copies/nucleus ≤ 5.0 (n = 534; 67%) and > 5.0 (n = 265; 33%) had HRs of 0.52 (P = .002) and 0.48 (P = .02), respectively (interaction P = .94). Patients with MYC:CEP8 ratio < 1.3 with normal chromosome 8 copy number (n = 141; 18%) and ≥ 1.3 or < 1.3 with polysomy 8 (n = 658; 82%) had HRs of 0.66 (P = .28) and 0.44 (P < .001), respectively (interaction P = .23). Patients with MYC copies/nucleus < 2.5 (n = 130; 16%) and ≥ 2.5 (n = 669; 84%) had HRs of 1.07 (P = .87) and 0.42 (P < .001), respectively (interaction P = .05). Conclusion: We did not confirm the B31 association between MYC amplification and additional trastuzumab benefit. Exploratory analyses revealed potential associations between alternative MYC/chromosome 8 copy number alterations and differential benefit of adjuvant trastuzumab.

Original languageEnglish (US)
Pages (from-to)651-659
Number of pages9
JournalJournal of Clinical Oncology
Volume29
Issue number6
DOIs
StatePublished - Feb 20 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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