Impact of c-MYC protein expression on outcome of patients with early-stage HER2+ breast cancer treated with adjuvant trastuzumab NCCTG (Alliance) N9831

Amylou C. Dueck, Monica M. Reinholz, Xochiquetzal J. Geiger, Kathleen Tenner, Karla Ballman, Robert B. Jenkins, Darren Riehle, Beiyun Chen, Ann E. McCullough, Nancy E. Davidson, Silvana Martino, George W. Sledge, Peter A. Kaufman, Leila A. Kutteh, Julie Gralow, Lyndsay N. Harris, James N. Ingle, Wilma L. Lingle, Edith A. Perez

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Abstract

Purpose: This study investigated the association between tumorMYCprotein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2+ trastuzumab breast cancer trial. Experimental Design: This analysis included 1,736 patients randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was determined in tissue microarray sections containing three biopsies per patient or whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor was considered positive for MYC protein overexpression (MYC+) if the nuclear 3+ staining percentage was more than 30%. Results: Five hundred and seventy-four (33%) tumors were MYC+. MYC+ was associated with hormone receptor positivity (χ2, P = 0.006), tumors 2 cm or more (χ2, P = 0.02), and a higher rate of nodal positivity (χ2, P < 0.001).HRs for DFS (median follow-up: 6.1 years) for Arm Cversus Awere 0.52 (P=0.006) and 0.65 (P =0.006) for patients with MYC+ and MYC - tumors, respectively (Pinteraction=0.40). For Arm B versus A, HRs for patients with MYC+ and MYC- tumors were 0.79 (P = 0.21) and 0.74 (P = 0.04), respectively (Pinteraction=0.71) . For Arm C versus B, HRs for patients with MYC+ and MYC- tumors were 0.56 (P=0.02) and 0.89 (P = 0.49), respectively (Pinteraction = 0.17). Conclusions: Our data do not support an impact of tumorMYCprotein expression on differential benefit from adjuvant trastuzumab.

Original languageEnglish (US)
Pages (from-to)5798-5807
Number of pages10
JournalClinical Cancer Research
Volume19
Issue number20
DOIs
StatePublished - Oct 15 2013

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dueck, A. C., Reinholz, M. M., Geiger, X. J., Tenner, K., Ballman, K., Jenkins, R. B., Riehle, D., Chen, B., McCullough, A. E., Davidson, N. E., Martino, S., Sledge, G. W., Kaufman, P. A., Kutteh, L. A., Gralow, J., Harris, L. N., Ingle, J. N., Lingle, W. L., & Perez, E. A. (2013). Impact of c-MYC protein expression on outcome of patients with early-stage HER2+ breast cancer treated with adjuvant trastuzumab NCCTG (Alliance) N9831. Clinical Cancer Research, 19(20), 5798-5807. https://doi.org/10.1158/1078-0432.CCR-13-0558