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Detection of circulating cancer cells in peripheral blood as a prognostic factor in early breast cancer

Background

Approximately 30% of patients with localized breast cancer eventually develop distant metastases despite optimal surgery and adjuvant therapies. This fact has been attributed to early tumor seeding via the bloodstream. Therefore, identification of breast cancer cells in blood could enable early detection of micrometastases and could potentially be of prognostic significance. The aim of our study was to evaluate the correlation between circulating breast cancer cells and classical prognostic factors.

Methods

From February 1999 until April 2004 blood samples from 81 patients, aged 36–72, stages I and II, with or without metastases to regional lymph nodes, were collected every 3–6 months. All patients underwent therapeutic surgery and subsequent adjuvant therapies. Blood samples were screened for mRNA encoding hMAM, EGFR, CK-19 and β-hCG by nested RT-PCR. The result of the test was treated as positive when the expression of one or more mRNA markers was observed in at least two samples taken from the same patient. Clinical data, such as histological grade, pT-grade and pN-grade, menopausal status, estrogen receptor and progesterone receptor status, malignancy grade and others were available for analysis.

Results

We found that breast cancer cells were present in peripheral blood of patients even in very early stages of the disease. Any of the two-marker tests used in our experiments, hMAM/β-hCG, hMAM/EGFR or EGFR/β-hCG, allowed comparable detection of breast cancer cells: in 68–74% of lymph node-positive (N1) and 49–59% of lymph node-negative (N0) patients. Addition of a third marker did not significantly increase detection sensitivity. While analyzing the presence of cancer cells in blood samples collected before mastectomy, we found cancer cells in the blood of only 13% of N0 patients, but in 46% of N1 patients. Thirteen of the 81 patients (16%) experienced recurrence of the disease within a 4-year follow-up period. We did not find any correlation between the presence of cancer cells and recurrence or any other clinical prognostic factors except one: patients with premenopausal status had cancer cells in the blood in 37% of cases, in comparison with those with postmenopausal status who had cancer cells in 63% of cases.

Conclusion

We have shown that a two-marker RT-PCR assay for hMAM/β-hCG, hMAM/EGFR or EGFR/β-hCG may be used for detection of occult breast cancer cells in peripheral blood. Except for menopausal status, we did not find any correlation between the presence of cancer cells in the blood and classical prognostic factors. Our data may suggest a different mechanism of disease dissemination in premenopausal and postmenopausal women.

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Fabisiewicz, A., Kober, P., Koptyra, M. et al. Detection of circulating cancer cells in peripheral blood as a prognostic factor in early breast cancer. Breast Cancer Res 7 (Suppl 2), P5.01 (2005). https://0-doi-org.brum.beds.ac.uk/10.1186/bcr1182

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  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/bcr1182

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