Molecular Genetic Basis of Invasive Breast Cancer Risk Associated With Lobular Carcinoma in Situ
LCIS) is a monoclonal pathologic entity which is subject to characterization at the
molecular genetic level, and that these molecular genetic alterations may be used to predict
the subsequent development of invasive breast cancer. Prophylactic mastectomy specimens from
women with multifocal LCIS, and invasive breast cancer specimens which display coexisting
LCIS, will be examined for X-chromosome inactivation patterns and loss of heterozygosity to
assess for monoclonality. If clonality is present, we will assess for microsatellite
instability, and a microarray-based comparative genomic hybridization (CGH) technique will
be used to identify genetic alterations present in LCIS. Lastly, LCIS biopsy specimens from
untreated patients who, after follow-up did or did not develop invasive breast cancer, will
be evaluated to determine whether the nature or extent of any identified genetic alterations
can be correlated with the subsequent development of invasive breast cancer. We hypothesize
that a fraction of LCIS lesions will reflect a monoclonal origin, that those lesions of
monoclonal origin will display evidence of specific molecular genetic alterations, and that
these specific alterations will correlate with the likelihood of the subsequent development
of invasive breast carcinoma.
Observational Model: Cohort, Time Perspective: Prospective
To perform analyses using microarray-based gene expression profiling to determine whether a unique mRNA and microRNA gene expression profile distinguishes LCIS from normal breast epithelium and from invasive carcinoma.
Tari King, M.D.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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