Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study

Abstract

BackgroundDisseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer.MethodsBetween 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately.ResultsDTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63–2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09–8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples.ConclusionsThe detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.

St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up

“…The study cohort was based on patients included previously in a prospective observational study on the prognostic value of analysing disseminated tumour cells in bone marrow17. Briefly, women diagnosed with an unifocal breast cancer between 1999 and 2003 in the Southern Swedish Health Care Region were identified.…”

The combination of Ki67, histological grade and estrogen receptor status identifies a low-risk group among 1,854 chemo-naïve women with N0/N1 primary breast cancer

“…The original study included 569 consecutive patients diagnosed with primary breast cancer in the South Swedish Health Care Region and included patients diagnosed between 1999 and 2003. The purpose was to study the prognostic value of the presence of cytokeratin positive cells in bone marrow aspirates from the sternum (Falck et al 2012). …”

“…ER, PgR, Ki67, HER2, and histological grade were analyzed and evaluated as described elsewhere (Ahlin et al 2009; Rydén et al 2005; Chebil et al 2003; Borgquist et al 2008; Falck et al 2012). If previously defined cut-points were available, they were used in the present study.…”

Expression of epithelial-mesenchymal transition-related markers and phenotypes during breast cancer progression

“…The present study is based on a subset of breast cancer patients previously included in a prospective observational study originally evaluating the presence and prognostic value of disseminated tumor cells in bone marrow [25]. A total of 569 primary breast cancer patients diagnosed between 1999 and 2003 were included (South Swedish Health Care Region: Lund, Landskrona, Helsingborg), and the study will in the following be referred to as the Bone Marrow Metastases (BMM) cohort [25]. The study was approved by the Lund University ethics committee (LU699-09, LU75-02), and all patients included provided written informed consent.…”