Behind the Paper - Breast cancer: Circulating cell counts predict chemo response

Discover the story behind our paper, "The lack of increases in circulating endothelial progenitor cell as a negative predictor for pathological response to neoadjuvant chemotherapy in breast cancer patients", which was published in npj Precision Oncology

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Our article entitled "The lack of increases in circulating endothelial progenitor cell as a negative predictor for pathological response to neoadjuvant chemotherapy in breast cancer patients" was published in the journal npj Precision Oncology. The Nature Research team had a few questions for us about our article, which we have answered below.

What was the main aim of your research and why did you decide to investigate this?

The prediction and monitoring of therapeutic effect are important to improve treatment efficacy and to avoid unnecessary toxicity during neoadjuvant chemotherapy. It is well recognized that tumor proliferation is accompanied by angiogenesis. Therefore, we considered that tumor angiogenesis might be changed during neoadjuvant chemotherapy.

It has been reported that CEPs are involved in angiogenesis; however, the alteration and kinetics of CEPs during neoadjuvant chemotherapy was unknown. That is why this study was aimed at assessing CEPs during neoadjuvant chemotherapy.


Why study CEPs in relation to cancer?

New growth in the vascular network is essential for cancer proliferation because cancer cells require an adequate supply of oxygen and nutrients. CEPs are mobilized from bone marrow as needed to form new vascular network.

We considered that the number of CEPs could be a candidate for representing angiogenesis.


Do the CEPs have anything to do with tumor angiogenesis?

As mentioned above, CEPs promote vascular generation and repair vasculature.


What challenges did you face?

There has been no standard systems to identify CEPs. We tried to identify CEP population most useful for treatment monitoring using several different combinations of cell surface markers.  In addition, in order to prevent loss of CEPs, blood was treated immediately after blood collection.

What were the key findings from your research?

In this study, we found that the alterations of CEP counts were associated with pathological response to NAC in patients with breast cancer.  The increase in CEP counts was observed in patient with pCR while not in those with non-pCR.

CEP count could be a useful biomarker for monitoring chemotherapeutic response.


Could radiation therapy also affect CEPs in a similar way or is this specific to the response to chemotherapy/certain chemotherapy agents?

Yes, although the definition of CEP was different from our study (colony formation), there is a report showing dose-dependent decrease of CEPs by radiation in patients with hyperthyroidism or thyroid cancer. (Barbara Palumbo et al, Nuclear Medicine Review 2003, Vol. 6 )It is unclear whether the alteration of CEPs was associated with treatment response to radiotherapy. Thus, further studies are clearly needed to investigate the clinical usefulness of CEPs with different treatment modalities.


What next? What further research is needed in this area?

Angiogenesis plays essential roles in both normal and pathological conditions but the differences in CEP biology between normal and cancerous conditions are unclear. It will lead to better understanding of tumor angiogenesis and improved monitoring efficiency to clarify the molecular differences in CEPs induced by cancer and by physiological conditions such as menstrual cycle. Furthermore, it will lead to a new treatment strategy targeting angiogenesis. Thus, it is important to clarify molecular profiles of CEPs under different conditions.

Read the article in full

Takayuki Ueno

Director, Cancer Institute Hospital