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NPJ Breast Cancer. 2019 Mar 21;5:10. doi: 10.1038/s41523-019-0105-y. eCollection 2019.

AKT1low quiescent cancer cells in ductal carcinoma in situ of the breast.

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1Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215 USA.
2Cancer Prevention and Control Program, Catalan Institute of Oncology (ICO), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.
3Department of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA 02215 USA.
4Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 USA.
5Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114 USA.
Contributed equally


Ductal carcinoma in situ (DCIS) of the breast precedes the development of invasive breast cancer and reflects the genomic changes and protein expression profile of invasive disease. AKT1low cancer cells (QCC) are a rare, drug-tolerant, epigenetically plastic, and quiescent cancer cell subset that we previously identified at a frequency of 0.5-1% in primary breast tumors using the marker profile: AKTlow/H3K9me2low/HES1high. Here we used quantitative immunofluorescence microscopy with computational image analysis to show that AKT1low QCCs are present in DCIS from patients with and without co-existing invasive breast cancer. These data suggest that a drug-resistant, quiescent cancer cell state is present in premalignant breast lesions prior to the development of invasive disease. These findings warrant further study of whether AKT1low QCCs contribute to invasive tumor development and recurrence, similar to their role in more advanced malignancy.

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