36 Correlation Between Disseminated Cancer Cells and DCISionRT Predictor Score in Patients With Ductal Carcinoma in Situ

Background

Dissemination of metastasis-initiating cancer cells, also known as disseminated cancer cells (DCCs), from the primary tumor in patients with breast cancer leads to invasion of distant organs. DCCs serve as a source of overt metastasis and recurrence in patients with invasive breast cancer, but their presence and significance in patients with ductal carcinoma in situ (DCIS) is unknown. Local recurrence risk for DCIS can be evaluated by a 10-year radiation therapy predictor score using clinicopathologic features in combination with a 7-gene biosignature to generate a DCISionRT score (DRT). DRT scores classify patients as low risk, elevated risk, and residual risk (highest risk) for in-breast recurrence. We evaluated the relationship between isolated DCCs in patients with DCIS with DRT scores undergoing breast-conserving surgery.

Materials and Methods

This is an institutional review board–approved, single-institution, prospective study of patients undergoing breast-conserving surgery for newly diagnosed DCIS. After informed consent, a one-time 10 to 20 mL perioperative bone marrow (BM) aspiration was obtained. All patients had DCIS; cases with microinvasive disease at resection were excluded. All patients had a DRT score. A DRT score of 0 to 3 was classified as low risk and 3 to 10 signified an elevated risk of local recurrence (elevated- or residual-risk type). DRT scores were obtained from preoperative core biopsy or surgical resection specimens. BM aspirates were processed and analyzed for epithelial cell adhesion molecule–expressing (EpCAM+) DCC. Detectable DCCs were quantified as greater than 400 isolated cells/mL of BM. Clinical and pathologic data were collected, including estrogen/progesterone receptor status, HER2/neu status, and histologic grade.

Results

Forty-two patients with DCIS underwent BM aspiration and had DRT scores. Also, 71.4% of total patients had detectable DCCs (range, 513-10,063 EpCAM+DCCs/mL BM); patients classified as residual-risk type were shown to have significantly higher BM-DCCs compared with low risk DRT (P <.0494) and compared with elevated risk (P = .0274; Figure). One-hundred-percent of the 10 residual risk–type patients had detectable DCCs compared with low-risk patients (n = 9 of the 14 low risk; 64.3% cases had detectable DCCs) and elevated-risk patients (n = 11 of the 18 elevated risk; 61.1% cases had detectable DCCs). No statistically significant differences were observed in DCC levels across histologic grades, age, or receptor status.

Conclusions

We identified DCCs in the vast majority of patients with DCIS. These DCCs further correlated with a commercially available, gene expression–based radiation therapy predictor score. Interestingly, elevated DCC level was significantly correlated with the residual risk–type population, suggesting that the quantity and detection of DCCs are related to high-risk disease, even without evidence of invasion. Further investigation into the significance of DCC-driven recurrence risk in early breast cancer is warranted.