CTCs Linked to Poor Early Breast Cancer Prognosis

The presence of circulating tumour cells in breast cancer patients is significantly associated with survival

medwireNews: Patients with early breast cancer who have circulating tumour cells (CTCs) before and after adjuvant chemotherapy are at increased risk of poor survival outcomes, German researchers say.

The 21.5% of patients in their study with CTCs before chemotherapy were more likely to have lymph node-positive disease than those without CTCs at this time point (22.4 vs 19.6%), although they did not significantly differ by tumour grade and size or hormone Receptor status.

And after a median of 35 months, patients with CTCs before chemotherapy had significantly poorer outcomes than those without CTCs in terms of disease-free survival (DFS), distant DFS (at 36 months), breast cancer-specific survival and overall survival.

Multivariate analysis confirmed that presence of CTCs at baseline was a significant predictor of poor DFS (hazard ratio [HR]=2.11) and overall survival (HR=2.18), with the poorest prognoses for patients with five or more CTCs per 30 mL of blood (HR=4.51 and 3.60, respectively).

Moreover, 22.1% of patients were positive for CTCs after completing chemotherapy and this was also an indicator of poorer DFS (HR=1.12) and overall survival (HR=1.16), say Brigitte Rack, from Ludwig-Maximilians University in Munich, and co-workers.

“Our data offer support for the clinical potential of CTCs to assess the individual risk of patients at the time of primary diagnosis and may be used for treatment tailoring in the absence of other strong quantitative markers”, the team writes in the Journal of the National Cancer Institute.

For the study, samples from 2026 patients with stage 1 to 3 breast cancer and N0 to N3 disease were analysed for cells expressing the epithelial-cell adhesion molecule, with CTCs defined as those without CD45 but with cytokeratin, the researchers explain.

They believe that further development of CTC analysis could allow phenotyping to identify cells associated with metastasis, as well as potential treatment targets or indicators of resistance, so that “the use of CTCs may considerably contribute to the personalization of breast cancer treatment”.

In an accompanying comment, Arnold Schwartz and Norris Nolan, from The George Washington University in Washington D.C, USA, say the study is “notable” for the large cohort size, the focus on early breast cancer and the use of both pre- and post-chemotherapy assessment.

They highlight the need to further develop CTC analysis to ensure all relevant cells are captured and that the tests are reproducible, allowing the development of decision analysis algorithms in the clinic.

“Additional studies and clinical experience will be needed to show that CTC assessment as a Biomarker will have a satisfactory cost–benefit ratio and provide useful information for the management of breast cancer patients”, they conclude.

References

Rack B, Schindlbeck C, Juckstock J, et al. Circulating Tumor Cells Predict Survival in Early Average-to-High Risk Breast Cancer Patients. JNCI 2014; First published online 15 May. DOI:10.1093/jnci/dju066

Schwartz A, Nolan N. Circulating Tumor Cells: What Goes Around, Comes Around.JNCI 2014; First published online 15 May. doi: 10.1093/jnci/dju108

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