A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer

Blau CA, Ramirez AB, Blau S, Pritchard CC, Dorschner MO, Schmechel SC, et al.

Journal of the National Comprehensive Cancer Network. 2016;14(1):8-17. DOI 10.6004/jnccn.2016.0003. PMID 26733551. PMCID PMC4970582.

How to cite

AMA

Blau CA, Ramirez AB, Blau S, Pritchard CC, Dorschner MO, Schmechel SC, et al. A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer. J Natl Compr Canc Netw. 2016;14(1):8-17. doi:10.6004/jnccn.2016.0003

APA

Blau, C. A., Ramirez, A. B., Blau, S., Pritchard, C. C., Dorschner, M. O., Schmechel, S. C., et al. (2016). A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer. Journal of the National Comprehensive Cancer Network, 14(1), 8-17. https://doi.org/10.6004/jnccn.2016.0003

BibTeX

@article{blau2016distributed,
  title   = {A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer},
  author  = {Blau, C. A. and Ramirez, A. B. and Blau, S. and Pritchard, C. C. and Dorschner, M. O. and Schmechel, S. C. and others},
  journal = {Journal of the National Comprehensive Cancer Network},
  volume  = {14},
  number  = {1},
  pages   = {8--17},
  year    = {2016},
  doi     = {10.6004/jnccn.2016.0003},
  pmid    = {26733551}
}

Judging whether a treatment is working in breast cancer that has spread to bone is hard. Standard imaging changes slowly, and a bone-marrow biopsy is a single snapshot of a moving target.

In this ITOMIC-001 report, a distributed network of 32 researchers from 14 institutions followed one patient with metastatic triple-negative breast cancer, sampling her circulating tumor cells 48 times over 9 months alongside whole-exome and RNA sequencing and a differential drug screen. The CTC counts — total cells, fragments and clusters — tracked her response to cisplatin, crizotinib and eribulin more sensitively than conventional blood markers.

A rise in CTC clusters preceded her death, and a drug screen run on her enriched CTCs pointed to vulnerabilities a single biopsy would have missed.

Key findings

  • Circulating tumor cells were monitored 48 times across 9 months in a single patient. A distributed network of 32 researchers from 14 institutions tracked total CTCs (about 1,500/mL at baseline), CD45−/EpCAM+/CK+ CTC fragments and CTC clusters as a longitudinal readout of response.
  • CTC dynamics tracked therapy response more sensitively than standard markers. Seven days after the first cisplatin dose, CTC fragments rose more than 100-fold; both CTCs and fragments then fell more than 650-fold and 3,500-fold respectively, ahead of changes in the CA15-3 blood marker.
  • A differential drug screen on enriched CTCs flagged BH3-mimetic sensitivity. Of 160 drugs tested on about 70 million CTCs enriched to roughly 12% purity, only the BCL-2 inhibitors ABT-263 and ABT-737 showed preferential activity, a signal reproduced across 20 triple-negative breast cancer cell lines (r=0.89).

RareCyte in the methods

“Assessments of circulating tumor cells (CTCs) were performed as described.”

— Blau et al., Journal of the National Comprehensive Cancer Network (2016), Methods, “Circulating Tumor Cell Assays”

Disclosure: RareCyte is listed as an author affiliation on the publication cited above.

Why it matters for RareCyte users

If you follow patients with rare circulating tumor cells, read this for what a repeated CTC measurement can carry. Here it caught response, resistance and relapse across 48 timepoints, when the standard blood marker lagged behind. One thing to be clear about as you weigh it. This paper does not name a CTC platform in its own methods; the assays were “performed as described,” pointing to an earlier protocol rather than to an instrument. What the record does add is that three of its authors work for RareCyte, noted in the disclosure below, and the method it cites is RareCyte’s own CTC-detection workflow. So take this as evidence for the kind of longitudinal rare-cell monitoring RareCyte is built around, not as a named-instrument benchmark. If that cadence fits your study — many timepoints from a single blood draw each — the value here is the time course, not any one count.