Disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: prognostic value and tumor phenotype

Objectives: Disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (BC) patients are a promising surrogate marker of micrometastatic spread and an independent predictor of poor prognosis for disease-free survival (DFS) and overall survival (OS). This study aims to analyze DTCs as an independent prognostic factor for disease free and overall survival in regard to the immunophenotype of the primary breast cancer.

Methods: 504 patients with operable primary BC and a medium observation time of 72 months have been included. DTCs were detected via immunohistochemistry as MUC-1 positive cells in the BM of 59.13% (298/504) of the patients.

Results: For Luminal A and Luminal B carcinomas, we observed a significant benefit of BM DTC negative patients with respect to DFS (Luminal A, p = 0.0498; Luminal B, p = 0.0224). In triple negative patients, DTC negative BM was associated with a longer OS (p = 0.0326).

We performed a multivariate Cox survival analysis in regard to DFS and OS with BM DTC status and luminal immunophenotypes as adjusted covariates. It implied DTC status (p < 0.0001) and Luminal A/B phenotype (p = 0.0071) as independent prognostic factors for disease free survival.

Conclusions: The findings of our multivariate analysis point out BM DTC positivity as an independent risk factor for disease free survival particularly in Luminal A/B BC patients. For this reason, luminal immunophenotype in combination with a DTC positive status might be a novel criterion for the identification of candidates most likely to benefit from additional adjuvant therapy, which might include extended adjuvant endocrine therapy.