Chromosomal copy number alterations for associations of ductal carcinoma in situ with invasive breast cancer
Year: 2015
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Screening mammography has contributed to a significant increase in the diagnosis of ductal carcinoma in situ (DCIS), raising concerns about overdiagnosis and overtreatment. Building on prior observations from lineage evolution analysis, we examined whether measuring genomic features of DCIS would predict association with invasive breast carcinoma (IBC). The long-term goal is to enhance standard clinicopathologic measures of low- versus high-risk DCIS and to enable risk-appropriate treatment. METHODS: We studied three common chromosomal copy number alterations (CNA) in IBC and designed fluorescence in situ hybridization-based assay to measure copy number at these loci in DCIS samples. Clinicopathologic data were extracted from the electronic medical records of Stanford Cancer Institute and linked to demographic data from the population-based California Cancer Registry; results were integrated with data from tissue microarrays of specimens containing DCIS that did not develop IBC versus DCIS with concurrent IBC. Multivariable logistic regression analysis was performed to describe associations of CNAs with these two groups of DCIS. RESULTS: We examined 271 patients with DCIS (120 that did not develop IBC and 151 with concurrent IBC) for the presence of 1q, 8q24 and 11q13 copy number gains. Compared to DCIS-only patients, patients with concurrent IBC had higher frequencies of CNAs in their DCIS samples. On multivariable analysis with conventional clinicopathologic features, the copy number gains were significantly associated with concurrent IBC. The state of two of the three copy number gains in DCIS was associated with a risk of IBC that was 9.07 times that of no copy number gains, and the presence of gains at all three genomic loci in DCIS was associated with a more than 17-fold risk (P = 0.0013). CONCLUSIONS: CNAs have the potential to improve the identification of high-risk DCIS, defined by presence of concurrent IBC. Expanding and validating this approach in both additional cross-sectional and longitudinal cohorts may enable improved risk stratification and risk-appropriate treatment in DCIS.
Source: Breast Cancer Research
Institutions: Stanford Medicine, Stanford University, VA Palo Alto Health Care System, Oregon Health & Science University, Cancer Prevention Institute of California, Dartmouth College, Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Health, Beth Israel Deaconess Medical Center, Harvard University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Breast Cancer Research Foundation, University of Southern California, National Institutes of Health, Centers for Disease Control and Prevention, National Cancer Institute, National Center for Research Resources, National Center for Chronic Disease Prevention and Health Promotion, National Center for Advancing Translational Sciences
Awards: G1516365345, G2089898225, G2238803135, Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, G2925750098, G3014186981, G3123501928, G3161224617, G3190882026, G3509688676, G4322373146, G4393609197, G4527459645, G480705112, G4861657729, CALIFORNIA'S PARTICIPATION IN THE NATIONAL CANCER PREVENTION AND CONTRO PROGRAM, G5333917095, G6246260791, G6795547015, G6906275629, G7195422766, G793654858
OpenAlex ID: W2133324883