Circulating Tumor Cells: Useful Tool in Metastatic Breast Cancer?

Zosia Chustecka

December 11, 2010

December 11, 2010 (San Antonio, Texas) — Measuring circulating tumor cells (CTCs) is a useful tool for managing patients with metastatic breast cancer, says one breast cancer expert, but another disagrees and says it adds nothing to the information that is already available clinically and from imaging.

This sharp difference in opinion emerged during a press conference here at the 33rd Annual San Antonio Breast Cancer Symposium, at which new data on CTCs from clinical trials in both metastatic and early breast cancer were being highlighted.

At present, there is only 1 CTC measuring system that is approved by the FDA: CellSearch (Veridex), which is indicated for use in metastatic breast cancer, as well as colorectal and prostate cancer. The approval was based on clinical trials that showed correlation between increases in CTC numbers and worse outcomes (both progression-free survival and overall survival).

Dr. Minetta Liu

Minetta Liu, MD, from Georgetown University, in Washington, DC, who moderated the press conference, says she uses this CTC system in her clinical practice as an additional tool, alongside imaging and clinical signs and symptoms, in the management of patients with metastatic breast cancer. For instance, a rise in a patient's CTCs could be seen as a "prompt" to consider changing treatment. It could also indicate that a closer look on imaging is needed, as "we may be missing something," she commented to Medscape Medical News.

As an example, Dr. Liu described a patient with stable metastatic breast cancer who was not displaying any new symptoms or headaches, but who suddenly showed an increase in CTCs. Imaging below the neck had already shown no new changes, but the CTC increase prompted Dr. Liu to scan the head, where she found brain metastases, which were treated with radiation. If it had not been for the CTC increase, she may not have looked there, she said.

However, another breast cancer expert at the press conference, Allison Stopeck, MD, from Arizona University, in Tuscon, declared that the technology was not useful clinically. Dr. Stopeck was involved in the development of the CellSearch system and in the clinical trials that led to approval, so she had the system in her clinic. However, she has since removed it, because she did not find it useful.

Dr. Allison Stopeck
"I don't need a number to tell me that a patient is progressing — this is not subtle in metastatic breast cancer," she said.

The main problem, Dr. Stopeck said, is that at present the CTC system is quantitative. The threshold is 5 CTCs/7 mL bood, above which patients have a poor prognosis, whereas if their CTC score is lower, they have a better prognosis. Dr. Stopeck says she has enough information from clinical signs and symptoms and imaging to determine prognosis without needing this extra bit of information.

In addition, she pointed out that about 30% to 40% of patients have no measureable CTCs, and yet their disease still progresses. "So having a zero score is not that informative," she said. In those cases, the cancer cells may be lying dormant in the bone marrow, she speculated.

"It's like looking for a needle in a haystack," she said.

Another reason for not using CTC measurement is that it costs $600 per test. "It may be something I would consider keeping on if it was $10 or $20 per test," she added.

She asserts that CTC measurement is "seldom used" clinically across the United States.

What she would like to see is qualitative information — for example, knowing that the CTCs express HER2+ or are hormone positive — as this information could be used to make treatment decisions, but such a system may be some way off as yet.

Dr. Leif Ellisen

Agreeing with this sentiment was Leif Ellisen, MD, PhD, from the Gillette Center for Breast Cancer at Harvard Medical School, in Boston, Massachusetts. It would be useful to have such qualitative information, as that could then direct treatment decisions, he commented to Medscape Medical News.

Dr. Ellisen uses CTC measurement in clinical trials, but not in clinical practice. He says that this technology is evolving and improving, but "still has some way to go." His team uses a CTC system developed at the Massachusetts General Hospital, which now uses a herringbone pattern CTC clip that is more accurate than the previous, column-based system.

Biggest Effect in Breast Cancer?

Dr. Ellisen predicted that the biggest effect of CTC measurement will be in early breast cancer. His team is conducting several trials in this patient population to see whether the number of CTCs, or changes in CTCs in the same patient, can be correlated with the likelihood of relapse.

There is an important question to answer here, he said. In a patient with early breast cancer who has finished therapy and appears to be doing well, should a sudden an increase in the number of CTCs prompt new treatment, and if so, what with?

This was also a question that came up in the press conference, where a German study of CTCs in patients with early breast cancer was presented by Briggitte Rack, MD, from the University of Munich, in Germany.

Dr. Rack and Dr. Liu both agreed that at present, CTC measurement in early breast cancer should be used only within a clinical trial setting.

They both pointed out that at this time, there is no evidence to support basing management decisions on CTC measurements in this patient population.

"It is not a tool to take home right now," Dr. Rack commented.

However, clinical trials are investigating this issue. At the meeting, Dr. Rack presented the latest data from a CTC analysis taken from ongoing study, the phase 3 SUCCESS trial.

This study is comparing different chemotherapy regimens, as well as extended adjuvant bisphosphonate treatment, in 2026 patients with early breast cancer. Efficacy results are expected to be released next year.

The data presented by Dr. Rack concern only the CTC portion of the trial, where patients were scored for CTC numbers (per 23 mL blood — a greater volume than in the metastatic setting, she noted). Patients with CTCs higher than 5 had a 4-fold risk for cancer recurrence and a 3-fold increase in risk for death from the disease compared with patients who had no CTCs, she reported.

However, CTCs were detected only in 21.5% of patients with early breast cancer before the start of adjuvant chemotherapy.

"Our study suggests that CTC testing may prove to be important to help individualize therapy for early-stage breast cancer where no measureable tumor is present," Dr. Rack said. "Patients who seem to be at high risk due to CTC may benefit from additional treatment options, and those that don't have CTCs may be spared the side effects of some treatments."

She emphasized, however, that this is still speculative. Prospectively randomized clinical trials are needed to show an improvement on survival based on CTC testing, and such trials are already in progress, both in the United States and in Europe, she said.

So for the time being, CTC testing remains in the realms of clinical trials for early breast cancer. The technology is now approved for use in metastatic breast cancer, but how useful it is clinically seems to be a matter of opinion.

Dr. Liu reported receiving research support from Veridex and Amgen. Dr. Stopeck reported acting as a consultant for Amgen and Novartis. Dr. Rack reported receiving research support from Veridex, Sanofi-Aventis, and Pfizer.

33rd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract 884. Presented December 10, 2010.


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