K. Takabe1, E. Katsuta1, L. Yan2, M. Nagahashi3 1Roswell Park Cancer Institute,Breast Surgery, Department Of Surgical Oncology,Buffalo, NY, USA 2Roswell Park Cancer Institute,Department Of Biostatistics And Bioinformatics,Buffalo, NY, USA 3Niigata University Graduate School Of Medical And Dental Sciences,Division Of Digestive And General Surgery,Niigata, , Japan
Introduction: Mutation of MYC that causes elevated expression of this oncogenic transcription factor is found in many cancers. This leads to the unregulated expression of many genes that result in cell proliferation and tumorigenesis. It has been reported that MYC amplification is associated with Triple Negative Breast Cancer (TNBC). However, clinical relevance of MYC amplification in breast cancer remains mostly unexplored. We hypothesized that high amplification of MYC is a prognostic biomarker that represent worse biology and poor survival.
Methods: Genomic and clinical data were obtained from the Cancer Genome Atlas (TCGA) through cBioportal. MYC amplification was defined based upon Genomic Identification of Significant Targets in Cancer (GISTIC) copy-number; GISTIC 2 was defined as tumor with amplification, remaining GISTIC -1, 0 and 1 were defined as tumor without amplification.
Results: Among 1080 patients with DNA copy-number data, 229 tumors (21.2%) showed MYC amplification which was the most common copy-number alteration in whole TCGA cohort of breast cancer. 156 patients (15.5%) were classified as TNBC based on ER, PgR, immunohistochemistry status and HER2 immunohistochemistry and FISH method. In agreement with previous report, there was greater proportion of tumors with high amplification of MYC in TNBC compared to non-TNBC (37% vs 18%, p<0.001). MYC mRNA expression was significantly higher in tumor with amplification compare to tumor without amplification in whole cohort as well as TNBC and non-TNBC (p<0.001, p=0.002 and p<0.001, respectively). There was no significant difference in overall survival (OS) between tumor with vs without amplification in whole breast cohort (p=0.112). To our surprise, tumors with high amplification showed significantly worse prognosis in non-TNBC patients (5-year OS rates: 80.2% vs 86.6%, p<0.037), whereas there was no significant difference in TNBC (p=0.68). These findings imply that altered MYC plays a role to promote cancer progression in non-TNBC. In non-TNBC cohort, there was greater proportion of higher AJCC Stage patients in tumors with MYC amplification group (Stage III/IV: 35.9% vs 24.8%, p<0.007).
Conclusion: Breast tumors with MYC amplification has worse prognosis in non-TNBC, but not in TNBC. MYC amplification may play different role between TNBC and non-TNBC.