51. Genomic landscape of ductal carcinoma in situ and association with progression
- Author
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Henning Stehr, Sushama Varma, Robert B. West, Sujay Vennam, Eric Y. Lin, Tina Seto, Allison W. Kurian, Megan L. Troxell, Natasha Purington, Summer S. Han, Chieh Yu Lin, Manisha Desa, and Nicholas J. Wang
- Subjects
0301 basic medicine ,Oncology ,In situ ,Cancer Research ,medicine.medical_specialty ,DNA Copy Number Variations ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Neoplasm Metastasis ,skin and connective tissue diseases ,neoplasms ,Exome sequencing ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Carcinoma, Ductal, Breast ,Chromosome ,Odds ratio ,Genomics ,Ductal carcinoma ,Middle Aged ,medicine.disease ,Tumor Burden ,body regions ,030104 developmental biology ,Carcinoma, Intraductal, Noninfiltrating ,030220 oncology & carcinogenesis ,Female ,business ,Fluorescence in situ hybridization ,Genome-Wide Association Study - Abstract
PURPOSE: The detection rate of breast ductal carcinoma in situ (DCIS) has increased significantly, raising the concern that DCIS is over-diagnosed and over-treated. Therefore, there is an unmet clinical need to better predict the risk of progression among DCIS patients. Our hypothesis is that by combining molecular signatures with clinicopathologic features, we can elucidate the biology of breast cancer progression, and risk-stratify patients with DCIS. METHODS: Targeted exon-sequencing with a custom panel of 223 genes/regions was performed for 125 DCIS cases. Among them, 60 were from cases having concurrent or subsequent invasive breast cancer (IBC) (DCIS+IBC group), and 65 from cases with no IBC development over a median follow-up of 13 years (DCIS-only group). Copy number alterations in chromosome 1q32, 8q24, 11q13 were analyzed using fluorescence in situ hybridization (FISH). Multivariable logistic regression models were fit to the outcome of DCIS progression to IBC as a function of demographic and clinical features. RESULTS: We observed recurrent variants of known IBC-related mutations, and the most commonly mutated genes in DCIS were PIK3CA (34.4%) and TP53 (18.4%). There was an inverse association between PIK3CA kinase domain mutations and progression (Odds Ratio [OR]=10.2, p
- Published
- 2019