Absence of Histologic Differences between Benign Breast Tissue from BRCA Carriers and Controls Despite Differential Gene Expression.
Linda Feeley, Louise Bordeleau, Suzanne Richter, Frances O'Malley, Dushanti Pinnaduwage, Lucine Collins, Bruce Youngson, Gord Glendon, Melinda Musgrave, James Mahoney, Wey Leong, Joan Lipa, David McCready, Irene Andrulis, Anna Marie Mulligan. St Michael's Hospital, Toronto, Canada; University of Toronto, ON, Canada; Oncology, McMaster University, Hamilton, Canada; Cancer Care Ontario, Toronto, Canada; University of California, Los Angeles, Canada; Samuel Lunenfeld Research Institute, Toronto, Canada
Background: Prophylactic mastectomy (PM) is an effective risk reducing strategy in BRCA1/2 mutation carriers. The objective of this study was to compare histologic findings in PM specimens prior to the onset of breast cancer with those from healthy controls and to correlate these findings with gene expression profiles using microarray technology.
Design: We prospectively collected PM specimens from BRCA1/2 mutation carriers (n=21), and reduction mammoplasty (RM) specimens from healthy controls at population risk of breast cancer (n=13). Tissue samples were bisected with one half fresh frozen for molecular analyses to 1) enable global assessment of gene expression and 2) identify differences based on cellular function and biologic themes. The remaining half was fixed in formalin for histologic assessment.
Results: Invasive carcinoma was not identified. There were no significant differences in histologic findings between the 2 groups using Fischer exact test: PM: normal (n=8), non-proliferative breast disease (n=7), proliferative breast disease (n=6); RM: normal (n=5), non-proliferative breast disease (n=4), proliferative breast disease (n=2), lobular neoplasia (n=2). Class comparison identified differential gene expression between RM and PM tissues with overexpression of genes relating to proliferation and transcription specifically in the PM tissues. Immunohistochemistry to examine differences in protein expression is in progress.
Conclusions: We found differential gene expression between benign breast tissue from BRCA1/2 mutation carriers and healthy controls without identifiable morphologic correlates on routine histologic examination. These findings suggest that early molecular changes in patients with hereditary breast cancer precede the development of detectable histological precursor lesions.
Tuesday, March 1, 2011 8:45 AM
Platform Session: Section C, Tuesday Morning