Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Sep 11:12:403.
doi: 10.1186/1471-2407-12-403.

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

Anna-Karin Falck  1 , Pär-Ola Bendahl, Christian Ingvar, Jorma Isola, Per-Ebbe Jönsson, Pia Lindblom, Kristina Lövgren, Karin Rennstam, Mårten Fernö, Lisa Rydén
Affiliations

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

Anna-Karin Falck et al. BMC Cancer. .

Abstract

Background: Disseminated 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.

Methods: Between 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.

Results: DTCs 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.

Conclusions: The 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Cytokeratin staining of DTCs isolated from bone marrow by immunofluorescence.
Figure 2
Figure 2
Cytokeratin staining of DTCs isolated from bone marrow by immunocytochemistry.
Figure 3
Figure 3
Distant disease-free survival (DDFS) in relation to presence of DTC.
Figure 4
Figure 4
Breast cancer-specific survival (BCSS) in relation to presence of DTC.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sveriges kommuner och Landsting S. Open comparisons of health care quality and efficiency: comparisons between counties in 2009. 2009. www.skl.se/publikationer.
    1. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20(8):1319–1329. doi: 10.1093/annonc/mdp322. - DOI - PMC - PubMed
    1. Gebauer G, Fehm T, Lang N, Jager W. Tumor size, axillary lymph node status and steroid receptor expression in breast cancer: prognostic relevance 5 years after surgery. Breast Cancer Res Treat. 2002;75(2):167–173. doi: 10.1023/A:1019601928290. - DOI - PubMed
    1. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347(8):567–575. doi: 10.1056/NEJMoa020128. - DOI - PubMed
    1. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB. et al.Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337(14):949–955. doi: 10.1056/NEJM199710023371401. - DOI - PubMed

Publication types