| Summary: | <p>Abstract</p> <p>Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among <it>BRCA1</it> mutation carriers. However, the exact mechanism by which RT reduces incidence of <it>BRCA1</it>-associated cancer remains unclear. Here we studied fresh breast tissue from a <it>BRCA1</it> 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 <it>in vitro</it>. Given the emerging evidence that <it>BRCA1</it> 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 <it>BRCA1</it>-associated cancer.</p>
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