PMID- 21245420 OWN - NLM STAT- MEDLINE DCOM- 20110401 LR - 20220311 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 29 IP - 6 DP - 2011 Feb 20 TI - 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. PG - 651-9 LID - 10.1200/JCO.2010.30.2125 [doi] AB - 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 = 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 = 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. FAU - Perez, Edith A AU - Perez EA AD - Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA. FAU - Jenkins, Robert B AU - Jenkins RB FAU - Dueck, Amylou C AU - Dueck AC FAU - Wiktor, Anne E AU - Wiktor AE FAU - Bedroske, Patrick P AU - Bedroske PP FAU - Anderson, S Keith AU - Anderson SK FAU - Ketterling, Rhett P AU - Ketterling RP FAU - Sukov, William R AU - Sukov WR FAU - Kanehira, Kazunori AU - Kanehira K FAU - Chen, Beiyun AU - Chen B FAU - Geiger, Xochiquetzal J AU - Geiger XJ FAU - Andorfer, Cathy A AU - Andorfer CA FAU - McCullough, Ann E AU - McCullough AE FAU - Davidson, Nancy E AU - Davidson NE FAU - Martino, Silvana AU - Martino S FAU - Sledge, George W AU - Sledge GW FAU - Kaufman, Peter A AU - Kaufman PA FAU - Kutteh, Leila A AU - Kutteh LA FAU - Gralow, Julie R AU - Gralow JR FAU - Harris, Lyndsay N AU - Harris LN FAU - Ingle, James N AU - Ingle JN FAU - Lingle, Wilma L AU - Lingle WL FAU - Reinholz, Monica M AU - Reinholz MM LA - eng SI - ClinicalTrials.gov/NCT00898898 GR - U24 CA114740/CA/NCI NIH HHS/United States GR - CA114740/CA/NCI NIH HHS/United States GR - CA25224/CA/NCI NIH HHS/United States GR - U10 CA025224/CA/NCI NIH HHS/United States GR - R01 CA129949/CA/NCI NIH HHS/United States GR - CA129949/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110118 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*therapeutic use MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Agents/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Breast Neoplasms/drug therapy/*genetics/*metabolism MH - Chemotherapy, Adjuvant MH - Cyclophosphamide/administration & dosage MH - Disease-Free Survival MH - Doxorubicin/administration & dosage MH - Female MH - Gene Dosage MH - Genes, erbB-2 MH - Genes, myc/*genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Middle Aged MH - Paclitaxel/administration & dosage MH - Proportional Hazards Models MH - Randomized Controlled Trials as Topic MH - Tissue Array Analysis MH - Trastuzumab MH - Treatment Outcome PMC - PMC3056653 COIS- Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. EDAT- 2011/01/20 06:00 MHDA- 2011/04/02 06:00 PMCR- 2012/02/20 CRDT- 2011/01/20 06:00 PHST- 2011/01/20 06:00 [entrez] PHST- 2011/01/20 06:00 [pubmed] PHST- 2011/04/02 06:00 [medline] PHST- 2012/02/20 00:00 [pmc-release] AID - JCO.2010.30.2125 [pii] AID - 02125 [pii] AID - 10.1200/JCO.2010.30.2125 [doi] PST - ppublish SO - J Clin Oncol. 2011 Feb 20;29(6):651-9. doi: 10.1200/JCO.2010.30.2125. Epub 2011 Jan 18.