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Genetic Link Confirmed Between DCIS And Invasive Disease

By LabMedica International staff writers
Posted on 28 Apr 2016
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Image: The Benchmark Ultra IHC/ISH staining instrument (Photo courtesy of Ventana Medical Systems).
Image: The Benchmark Ultra IHC/ISH staining instrument (Photo courtesy of Ventana Medical Systems).
Inherited genetic links have been confirmed between non-invasive cancerous changes found in the milk ducts, known as ductal carcinoma in situ (DCIS) and the development of invasive breast cancer, meaning that a family history of DCIS could be as important to assessing a woman's risk as a history of invasive breast cancer.

DCIS is a non-invasive form of early breast cancer, where cancerous cells are entirely contained within the milk ducts of the breast. In the UK, 5,000 women are diagnosed with DCIS each year with two thirds of these cases being diagnosed through routine breast screening, rather than symptomatic detection.

A large team of scientists led by those at King's College London (UK) pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of invasive ductal carcinoma (IDC) and 37,467 controls, all genotyped using the iCOGS chip. Women with all types of breast cancer were recruited. A total of 3,078 subjects were recruited following identification from local pathology reports in 97 UK hospitals.

After DNA extraction from peripheral blood, samples were genotyped on the iCOGS custom Illumina iSelect array (Illumina, San Diego, CA, USA), which contains 211,155 single nucleotide polymorphisms (SNPs). Data on grade of DCIS were available from histopathology reports for 828 cases. Information on cytonuclear grade of DCIS was available for 2,578 cases, mostly from the local histopathology reports. Estrogen receptor (ER) status from local histopathology reports was available for 1,086 cases. For the remaining 781 cases where the tumor block was available, immunohistochemistry was performed on 3-μM sections, which were incubated at 60 °C for one hour prior to automated staining using the VENTANA system, (Ventana Medical Systems, Inc, Oro Valley, AZ, USA).

Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near the Cyclin D1 (CCND1) gene were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC.

Elinor J. Sawyer, MD, PhD, a Clinical Oncologist and a senior author of the study, said, “This study provides the strongest evidence to date of a shared genetic susceptibility between DCIS and invasive ductal cancer, suggesting that both develop through a common pathway. This is a great leap in our understanding of DCIS, but it is also just the first step. We now hope to carry out a larger study assessing more genetic changes to discover whether there are any that predispose solely to DCIS, something that could help us predict whose non-invasive cancer is unlikely to progress.” The study was published on February 17, 2016, in the journal Breast Cancer Research.

Related Links:
King's College London
Illumina
Ventana Medical Systems
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