Circulating tumor cells or CTCs are the roots of metastasis which is the main cause of death in metastatic breast cancer (MBC). These cells are shed from both primary and secondary tumors and have demonstrated to be a robust independent prognostic factor of progression-free and overall survival in patients with early and metastatic breast cancer.[1]

CTC and other circulating tumor markers have advantages over tissue biopsy, including ease of collection, serial evaluation, and interrogation of the entire tumor burden instead of just a limited part of the tumor. Reviews of CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate, and colorectal cancers. [2]

According to a meta-analysis, supported by Menarini Silicon Biosystems, presented at the 2020 San Antonio Breast Cancer Symposium, held December 8-11, 2020, early circulating tumor cell dynamics were associated with overall survival in patients with metastatic breast cancer.[3]

“With the increasing number of treatment options available to patients with metastatic breast cancer, being able to predict and monitor treatment responses rapidly will be critical to aiding treatment decisions,” noted Wolfgang Janni, MD, Ph.D. , a professor, and director of the women’s clinic at Ulm University Hospital in Ulm, Germany.

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Responses to breast cancer treatment are typically monitored by conventional imaging, but this method requires time—approximately three months, depending on the subtype—before changes can be detected,

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“We were interested in determining whether treatment response and prognosis could be predicted earlier using a simple blood test,” Janni explained.

In this study, Janni and colleagues investigated the potential of circulating tumor cells, which are shed from the primary tumor into the bloodstream, to predict overall survival. The investigators analyzed global pooled datasets from peer-reviewed and published studies of 4,079 patients with metastatic breast cancer, all of whom had undergone baseline and follow-up CTC measurements using the CellSearch® CTC test (Menarini Silicon Biosystems), a simple, actionable blood test designed to helps oncologists assess the prognosis of patients with metastatic breast.

The median time from baseline to follow-up was 29 days. Changes in CTC levels between baseline and follow-up were analyzed to determine whether they were associated with overall survival.

Study design
Of the 2,961 patients who were CTC-positive at baseline, 1,855 remained CTC-positive after initiating treatment (positive/positive), and 1,106 patients had converted to CTC-negative (positive/negative). Of the 1,118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), while 305 had become CTC-positive (negative/positive).

Wolfgang Janni, MD, Ph.D. , a professor, and director of the women’s clinic at Ulm University Hospital in Ulm, Germany. Photo courtesey: © 2020 Universitätsklinikum Ulm, Germany.

Median overall survival was greatest for patients who were negative/negative (47 months), followed by positive/negative (32.2 months), negative/positive (29.67 months), and positive/positive (17.87 months).

Compared to patients who were negative/negative, the risk of death was 215% greater for those who were positive/positive, 74% greater for negative/positive, and 52% greater for positive/negative. For patients who were CTC-positive at baseline, those who remained CTC-positive at follow-up had a 51% greater risk of death than those who converted to CTC-negative.

Similar trends were found when CTC dynamics were analyzed by breast cancer subtype, including for hormone receptor-positive, HER2-positive, and triple-negative breast cancers. CTC dynamics were associated with overall survival for all breast cancer subtypes.

Clinical benefit
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni.

“This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”

“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni noted

“This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”

Study limitation
A limitation of the study is that information about the type of treatment received was not available for many patients.

“A strength of our study is that we have individual patient data from around the world, but this is also a limitation because different sources provided varying levels of details regarding treatment,” Janni concluded.

The absence of these data precluded determining whether the predictive value of CTC dynamics varies by treatment.

Reference
[1] Paoletti C, Hayes DF. Circulating Tumor Cells. Adv Exp Med Biol. 2016;882:235-58. doi: 10.1007/978-3-319-22909-6_10. PMID: 26987538.
[2] Cabel L, Proudhon C, Gortais H, Loirat D, Coussy F, Pierga JY, Bidard FC. Circulating tumor cells: clinical validity and utility. Int J Clin Oncol. 2017 Jun;22(3):421-430. doi: 10.1007/s10147-017-1105-2. Epub 2017 Feb 25. PMID: 28238187.
[3] Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) – a global pooled analysis with individual patient data. San Antonio Breast Cancer Symposium. SABCS | December 11, 2020, 10:45 AM – 11:00 AM | Session GS4 – General Session 4. (GS4-08). [Abstract]

Featured image: Attendees during the San Antonio Breast Cancer Symposium being held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Photo courtesy © 2019 AACR/SABCS Todd Buchanan

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