The prognostic significance of disseminated tumour cells in bone marrow in patients with operable breast cancer: An updated analysis

SUMMARY

The main cause of death in patients with breast cancer is the spread and outgrowth of tumour cells at distant sites. The presence of disseminated tumour cells (DTCs) in the bone marrow at diagnosis is a predictor for metastasis. This is an updated analysis of a prospective study in 100 patients with operable breast cancer on the long term-significance of bone marrow micrometastasis. The follow-up time ranges between one and 242 months, with a mean of 131 months and a median of 141 months. Bone marrow aspirates were analysed for the presence of DTCs by real-time polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and mammaglobin (MAM), as well as immunocytochemistry (ICC) for cytokeratin (CK). The aim of this study was to confirm the association between DTCs and disease-specific survival (DSS), as well as distant metastasis-free survival (DMFS).

CK19 positivity did not reach statistical significance for DSS (p=0.065) or DMFS (p=0.233). However, MAM positivity was significantly prognostic for DSS (HR: 5.583, p<0.001), but only borderline trending for DMFS (p=0.064). The combination of CK19 and MAM positivity, however, did confer a significantly increased risk for both DSS (HR: 3.073, p=0.003) and DMFS (HR: 3.150, p=0.023). ICC CK positivity significantly predicted DSS (HR: 3.868, p=0.040) or DMFS (HR: 3.868, p=0.040) when using a cut-off of ≥1 DTC. Stratifying the quantitative data also gave a significant result for DSS and DMFS (OR: 2.974, p=0.008). Combining both detection measurements using a cut-off of ≥1 DTC in immunochemical detection showed a significant association with DSS (HR: 3.213, p=0.089) and DMFS (HR: 4.984, p=0.015). Three negative parameters significantly predicted DSS (HR: 0.368, p= 0.017), but not DMFS. There was no statistically significant association of DTCs with organ-specific metastasis. This study supports the role of DTCs as a negative, prognostic factor in patients with operable breast cancer. The combination of multiple DTCs could be useful in identifying this increased risk.

(BELG J MED ONCOL 2023;17(3):71–84)