Translational Medicine

Translational Medicine
Open Access

ISSN: 2161-1025

DCIS in BRCA1 and BRCA2 mutation carriers: Prevalence, phenotype and expression of oncodrivers C-MET and HER3


14th Annual Conference on Translational Medicine and Oncologists Meet

November 28-30, 2016 San Francisco, USA

Rachel L Yang, Rosemarie Mick, Kathreen Lee, Holly L Graves, Katherine L Nathanson, Susan M Domchek, Rachel R Kelz, Paul J Zhang and Brian J Czerniecki

University of Pennsylvania, USA

Posters & Accepted Abstracts: Transl Med

Abstract :

Background: Studies report conflicting evidence regarding the existence of a (ductal carcinoma in situ) DCIS-associated premalignant pathway in BRCA mutation carriers. We aimed to examine the prevalence, phenotype and expression of oncodrivers in pure DCIS (pDCIS) and invasive breast cancer with concurrent DCIS (IBC+DCIS) in mutation carriers. Methods: A cohort of BRCA1 and BRCA2 mutation carriers >18 years old who underwent surgery for breast cancer at an academic hospital (1992-2011) and had pathology available for review were included for study. Invasive breast cancer (IBC) and DCIS were stained for ER, PR, HER1, HER2, and HER3, and C-MET. DCIS prevalence was evaluated. Correlation of IBC and DCIS phenotypes was evaluated in patients with IBC+DCIS. DCIS and IBC expression of tumor markers were examined by BRCA mutation. Results: We identified 114 breast tumors. Of all BRCA1-associated tumors, 21.1% were pDCIS and 63.4% were IBC+DCIS. Of all BRCA2-associated tumors, 23.3% were pDCIS and 60.5% were IBC+DCIS. In BRCA1 and BRCA2 mutation carriers with IBC+DCIS, there was a significant correlation in ER, PR, and HER3 expression between the DCIS and IBC components. Most BRCA1-associated DCIS did not express ER, PR or HER2, while most BRCA2-associated DCIS expressed ER and PR. BRCA1- as well as BRCA2-associated DCIS had expression of HER3 and C-MET. Conclusions: The majority of BRCA-associated tumors had DCIS present. Concordance of DCIS and IBC phenotypes was high, arguing for the existence of a DCIS-associated premalignant pathway. Oncodrivers HER3 and C-MET were expressed in the DCIS of mutation carriers, suggesting an opportunity for prevention strategies.

Biography :

Email: rlyang@stanford.edu

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