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Breast-conserving surgery for ductal carcinoma in situ (DCIS) is often combined with irradiation, reducing recurrence rates to 20% within 10 years; however, there is no change in overall survival. Evidence in the invasive breast indicates that breast cancer stem cells (CSCs) are radiotherapy-resistant and are capable of re-initiating a tumor recurrence; hence, targeting CSCs in high risk DCIS patient may improve survival. HER2 is overexpressed in 20% of DCIS and is known to be highly active in breast CSCs; we therefore investigated the effect of Lapatinib on DCIS CSC activity using 2 in vitro culture systems. Two DCIS cell lines DCIS.com (HER2 normal) and SUM225 (HER2 overexpressed) as well as DCIS cells from patient samples (n = 18) were cultured as mammospheres to assess CSC activity and in differentiated 3D-matrigel culture to determine effects within the non-CSCs. Mammosphere formation was reduced regardless of HER2 status, although this was more marked within the HER2-positive samples. When grown as differentiated DCIS acini in 3D-matrigel culture, Lapatinib only reduced acini size in the HER2-positive samples via decreased proliferation. Further investigation revealed lapatinib did not reduce self-renewal activity in the CSC population, but their proliferation was decreased regardless of HER2 status. In conclusion we show Lapatinib can reduce DCIS CSC activity, suggesting that the use of Lapatinib in high-risk DCIS patients has the potential to reduce recurrence and the progression of DCIS to invasive disease.

Original publication

DOI

10.4161/cc.27201

Type

Journal article

Journal

Cell cycle (Georgetown, Tex.)

Publication Date

01/2014

Volume

13

Pages

418 - 425

Addresses

Cancer Stem Cell Research; University of Manchester; Institute of Cancer Sciences; Manchester Academic Health Science Centre; Paterson Building; The Christie NHS Foundation Trust; Manchester, UK.

Keywords

Cell Line, Tumor, Humans, Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms, Quinazolines, Receptor, erbB-2, Antineoplastic Agents, Cell Proliferation, Female, Neoplastic Stem Cells, In Vitro Techniques