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Association of radiotherapy with preferential depletion of luminal epithelial cells in a BRCA1 mutation carrier

Huai-Chin Chiang1, Sreejith J Nair1, I-Tien Yeh2, Alfredo A Santillan2, Yanfen Hu1, Richard Elledge2 and Rong Li1*

Author Affiliations

1 Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78245, USA

2 Department of Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78245, USA

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Experimental Hematology & Oncology 2012, 1:31  doi:10.1186/2162-3619-1-31

Published: 8 October 2012


Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among BRCA1 mutation carriers. However, the exact mechanism by which RT reduces incidence of BRCA1-associated cancer remains unclear. Here we studied fresh breast tissue from a BRCA1 mutation carrier who was initially treated with a lumpectomy and RT for a unilateral cancer and two years later chose a prophylactic bilateral mastectomy while remaining cancer-free. Flow cytometry analysis demonstrated a strikingly lower luminal cell population in the irradiated breast as compared to the non-irradiated breast, which was confirmed by immunohistochemistry. Furthermore, the irradiated breast tissue exhibited very low progenitor cell activity in vitro. Given the emerging evidence that BRCA1 tumors originate from luminal progenitor cells, our observations suggest that preferential and long-lasting elimination of luminal ductal epithelium may partly underlie the mechanism of RT-associated reduction in recurrence of BRCA1-associated cancer.

Radiation; Luminal progenitor cells; Cell of origin; BRCA1