The European study follows a smaller prospective study in China and represents a “milestone” for CTC research, according to Massimo Cristofanilli, MD, of Thomas Jefferson University in Philadelphia, PA.10

The study’s authors also report that CTC counts 3 to 5 weeks after treatment initiation “clearly discriminated patients with indolent (treatment-sensitive) versus aggressive (treatment-resistant) disease,” Dr. Cristofanilli noted (median OS for patients with CTCs <5 per 7.5 mL at 3 to 5 weeks: 41.5 months [95% CI, 36.8-52.7 months] vs ≥5 CTCs per 7.5 mL: 13.1 months [95% CI, 9.4-16.4 months]).10,11


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“Taken together, these results confirm that CTCs are a powerful instrument for the personalized management of metastatic breast cancer, have strong clinical value, and are without any major limitations or contraindications,” Dr. Cristofanilli concluded.10

“Enumeration of CTCs was a better predictor of prognosis than the standard mucin-based serum biomarkers currently used for disease monitoring,” Dr. Cristofanilli noted.10

The new study means that CTC enumeration can help differentiate patients who will benefit from sequential standard treatments from those with intrinsically resistant disease who are unlikely to benefit from standard treatment, and those with refractory tumors, for whom alternative treatments should be developed—and that CTC measures should be incorporated into patient stratification for clinical trials, Dr. Cristofanilli believes.10

CTC measures might allow patients who are unlikely to benefit from standard treatment to forego unnecessary treatment-related side effects—and to confer with their clinicians about alternative treatments or enrollment in a clinical trial.

Technological advances for capturing and enumerating CTCs are proliferating.1,12 But for the time being, CTC detection outside clinical trials “should be limited to selected clinical situations,” such as risk stratification and assessment of likely treatment benefits among patients with increased treatment toxicities, advised Marianna Alunni-Fabbroni, MD, and colleagues at the University of Munich in Germany.13

Alongside promising developments in CTC enumeration, genetic, genomic, and proteomic analysis of CTCs—and even circulating tumor DNA14—have been proposed and are undergoing preclinical development.15

Such analyses are yielding new details about immune escape and tumor cell survival in metastatic processes—potential new targets for drug development that could one day result in agents that specifically disrupt metastasis.16 CTCs appear to be at center stage in drug resistance and the process of metastasis, with important roles in seeding of distant tumor sites, suggesting that their study can inform drug development for targeting specific subpopulations of CTCs, and ultimately, the metastatic process itself. CTCs appear to up- and downregulate specific gene pathways in a manner facilitating CTC immune escape and metastasis.16