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SAN ANTONIO BREAST CANCER SYMPOSIUM: Circulating Tumor Cells Linked to Worse Prognosis in Breast Cancer Patients

Laino, Charlene

doi: 10.1097/01.COT.0000394942.69362.f9

New research presented at the CTRC-AACR San Antonio Breast Cancer Symposium adds to growing evidence that higher levels of circulating tumor cells (CTCs) are associated with an increased risk for recurrence and death in metastatic breast cancer patients.

Another study suggests that the presence of even one CTC in the blood is associated with a worse prognosis in women with early-stage breast cancer.

Shortly after the meeting, Veridex, LLC—maker of the only test approved for use in metastatic breast cancer by the Food and Drug Administration—announced a collaboration with Massachusetts General Hospital to develop and commercialize a next-generation CTC technology for capturing, counting, and characterizing the cells.

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Metastatic Disease

In the first study, French researchers found that patients with metastatic breast cancer who have five or more tumor cells circulating in their blood after the first round of treatment have disease progression sooner than those who have fewer CTCs.

The work builds on findings showing that the presence of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival times in patients with metastatic breast cancer (Cristofanilli et al: NEJM 2004;351:781-791).

The new study is the largest prospective series validating the prognostic value of CTCs in metastatic breast cancer, and the CTCs predicted prognosis even after taking other markers of survival into account, noted Jean-Yves Pierga, MD, PhD, Professor of the Medical Oncology Department at Institut Curie and Université Paris Descartes.

The study also suggests that CTCs can be used to monitor whether a patient is responding to treatment, he added.

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Study Details

The researchers tested blood samples from 267 patients with metastatic disease undergoing first-line chemotherapy with or without bevacizumab.

Before treatment, 65% of the women had one or more CTCs; 44% had five or more CTCs.

After two years, cancer had progressed in 95% of those with five or more CTCs, compared with 70% of those with fewer or no CTCs.

Looked at another way, that shows that women with five or more CTCs were 90% more likely to have their cancer progress and nearly two-and-a-half times more likely to die, even after other tumor markers were taken into account, Dr. Pierga said.

“CTCs had prognostic value independent of other tumor biomarkers, including carcinoembryonic antigen, CA 15.3, and lactate dehydrogenase,” he said.

Then the researchers compared patients’ CTC levels after their first round of treatment and the risk of progression.

At two years, cancer had progressed in about 70% of those with fewer than five CTCs, but in all of those with more CTCs. Over 90% of those with fewer than five CTCs were still alive, compared with less than half of the women with more CTCs.

The study also showed that after three rounds of treatment, CTCs dropped more in women who received bevacizumab plus chemotherapy, compared with those who received chemotherapy alone.

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Early Breast Cancer

Also reported at the meeting, a study by German researchers found that having even one CTC in the blood increases the risk of recurrence and death in patients with early-stage breast cancer.

The study involved 2,026 patients with high-risk node-positive and node-negative early breast cancer. Following surgery, all patients received fluorouracil, epirubicin, and cyclophosphamide, and were then randomized to receive docetaxel alone or in combination with gemcitabine.

After completing adjuvant chemotherapy, the patients were randomized again to receive zoledronic acid, alone or in combination with endocrine therapy.

The patients were followed for a median of 35 months, during which time 114 had a recurrence and 66 died of breast cancer.

Results showed that 88% of patients who tested positive for CTCs after surgery were alive and free of disease at three years versus 94% of patients with no CTCs in their blood.

In multivariate analysis, a positive CTC test was associated with a 1.9-fold increased risk of relapse.

“We don't have markers for prognosis or to tell us if a treatment is working in early breast cancer,” said Brigitte Rack, MD, Head of the Department of Gynecological Oncology at the Women's Hospital at the University of Munich. “If we had an early marker, it could help us to see if a different treatment might be better.

“Our study suggests that testing for circulating tumor cells may prove to be important to help individualize therapy for early-stage breast cancer. Patients who seem to be at high risk due to circulating tumor cells may benefit from additional treatment options, and those who don't have circulating tumor cells may be spared side effects of some treatments,” she said.

Still, CTC testing is not ready for prime time in patients with early breast cancer, Dr. Rack said. “We don't know what options to offer if a woman does have CTCs.”

Several studies looking at whether CTC testing can extend survival in early breast cancer are now ongoing in Europe and the United States, Dr. Rack added.

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Doctors Divided

Oncologists at the meeting, though, were divided about whether they considered CTC testing to be useful even for its approved use in metastatic disease.

Alison T. Stopeck, MD, Director of the Clinical Breast Cancer Program at the Arizona Cancer Center, said she doesn't use the CTC test at all: “More often than not, I know which of my patients with metastatic breast cancer are progressing just by examining them,” she said.

In addition, unlike HER2 or estrogen-receptor status, a high CTC count doesn't provide any information about what treatment might help, she added.

But Minetta C. Liu, MD, Director of Translational Breast Cancer Research at Georgetown Lombardi Comprehensive Cancer Center, said the test is very useful: “I use every tool I have,” she said, explaining that in some cases, knowing a patient has no CTCs vallows her to delay much more expensive imaging tests to track the progress of the cancer, while in other cases, a rise in CTCs indicates imaging is needed.

Dr. Liu offered as an example a patient with stable metastatic breast cancer who experienced a sudden rise in CTCs. The increase led to a scan of the head, where brain metastases were found and treated with radiation.

Both studies utilized Veridex's CellSearch technology, which is approved for use in metastatic breast cancer, as well as colorectal and prostate cancer.

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New Partnership

News of the Veridex-Massachusetts General Hospital partnership to develop and study a new type of CTC blood test made headlines nationwide last month. MGH offi - cials said afterward that the original media reports erroneously stated that the test involved microchip technology.

In fact, MGH has already developed a microchip-based CTC screen that will be tested at Mass General, Memorial Sloan-Kettering Cancer Center, the University of Texas MD Anderson Cancer Center, and Dana-Farber Cancer Institute.

The new partnership is relying on a different, and as yet undisclosed, technology.

Asked if the announcement was blown out of proportion in the way it was generally reported by the media, Minetta C. Liu, MD, Director of Translational Breast Cancer Research at Georgetown Lombardi Comprehensive Cancer Center, said, “It's exciting any time we can advance a test further. But these are early days and whether they'll hit a home run is still anybody's guess.”

© 2011 Lippincott Williams & Wilkins, Inc.
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