CTCs May Predict Breast Cancer Recurrence

For patients diagnosed with stage II to III ER-positive, HER2-negative breast cancer, the presence of circulating tumor cells (CTC) several years afterward may increase the likelihood of their disease making a late comeback, according to a prospective analysis. The findings were presented by Joseph Sparano, MD, of Montefiore Einstein Center for Cancer Care in New York, NY, during the 2017 San Antonio Breast Cancer Symposium in Texas, held December 5–9.

“Late recurrence is generally defined as occurring 5 or more years after the initial diagnosis,” Sparano explained. “It accounts for about half of all recurrences with this breast cancer subtype, and is considered a huge clinical problem that some in our field have dubbed the next frontier for research.”

Since 2003, Sparano and his colleagues had been monitoring long-term outcomes in a large study of 4,950 patients who received taxane chemotherapy and, for those with ER-positive disease, at least 5 years of endocrine therapy. “As we were following them anyway, we asked if they'd be willing to provide a blood sample for CTC analysis,” he said. Between 2013 and 2016, a total of 547 patients were enrolled and had their CTCs measured using CellSearch (Menarini Silicon Biosystems), an FDA-cleared assay.

Overall, the percentages of patients whose CTC assay turned out positive “weren't very different between ER-positive [5.1%] and ER-negative [4.1%] groups,” Sparano observed. After a median follow-up of 1.8 years, however, the investigators found that whereas 14 of 353 ER-positive patients saw their disease return—all at distant sites in the body—there was just one case of local/regional recurrence among 193 ER-negative patients.

“It confirmed what we'd already thought—that ER-positive breast cancer is associated with a higher risk of recurrence,” Sparano said. He also noted that “because there were no distant recurrences in our ER-negative group, we don't currently know what a positive CTC assay result may mean here.”

Delving deeper into statistical analyses of the ER-positive cohort, Sparano reported that the risk of recurrence among those with CTCs detected in their blood “increased by nearly 22-fold, which is highly significant.” Meanwhile, “if a patient was CTC-negative, we calculated that there was less than a 2% chance their disease would return within the next 2 years,” he said.

Kent Osborne, MD, director of Baylor College of Medicine's Cancer Center in Houston, TX, called the study “intriguing.” It's not practice-changing, however, because “we don't yet know what to do with the data,” he added. Osborne also encouraged the investigators to continue probing additional factors, besides the presence of CTCs, that could affect the likelihood of recurrence.

Sparano agreed that “we still have work to do, to really nail down what the clinical utility of our findings may be.” One possible implication, he said, is that even though extended adjuvant endocrine therapy (beyond the recommended 5 years) has been shown to decrease late recurrence of ER-positive breast cancer by about 2% to 4%, perhaps CTC-negative patients could be spared further, unnecessary treatment.

“We do think our evidence so far supports CTCs as a biomarker of late recurrence in this breast cancer subtype, providing a very high level of risk stratification,” he concluded. “It also supports the concept of having a second decision point—not at the time of diagnosis, but some years later—to tailor therapy for individual patients.” –Alissa Poh

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