AKT1<sup>low</sup> quiescent cancer cells in ductal carcinoma in situ of the breast.

Overview

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. AKT1^low 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: AKT^low/H3K9me2^low/HES1^high. Here we used quantitative immunofluorescence microscopy with computational image analysis to show that AKT1^low 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 AKT1^low QCCs contribute to invasive tumor development and recurrence, similar to their role in more advanced malignancy.