LAS VEGAS – Although circulating tumor cells are prognostic in breast cancer, they aren’t likely to become a part of routine practice until they’ve been shown to improve outcomes, and that hasn’t happened yet, according to Anthony Lucci, MD, professor of breast surgical oncology at MD Anderson Cancer Center, Houston.
MD Anderson and other institutions have established that in breast cancer, from baseline through treatment follow-up, the presence of circulating tumor cells (CTCs) in the blood predicts worse outcomes in both metastatic and local disease, even among women who have a pathologic complete response to treatment.
Dr. Anthony Lucci
That knowledge has not yet translated into better outcomes. In a pivotal trial, survival was no better in metastatic breast cancer when women were switched to an alternative chemotherapy regimen after their CTC levels did not fall in response to first-line treatment, compared with women who remained on their initial agent despite persistently high CTCs (J Clin Oncol. 2014 Nov 1;32[31]:3483-9).
“When we tried to switch chemotherapy” based on CTCs, “it really didn’t make a difference, so no one is really quite sure yet what to do with this information. We can’t tell a patient that they are likely to have a much worse outcome, but there’s nothing we can do about it,” and “I don’t think payers will pay” for CTC testing in breast cancer until “we establish a predictive benefit, and show what agents will reduce CTCs and improve outcomes,” Dr. Lucci said at the American Society of Breast Surgeons annual meeting.
Even so, the promise of CTCs as a clinical tool is too great to abandon research, and work continues at MD Anderson and elsewhere. It’s thought that tumor cells in the blood aren’t simply a marker of disease, but rather microscopic disease in themselves that contributes to recurrence and progression. It’s possible that cells shed by tumors lie dormant in the bone marrow, then reactivate and reseed the original tumor site or give rise to distant metastases.
CTCs are similar to tumor cells that have been found in the bone marrow of women with apparently quiescent breast cancer, but finding them in the blood means “you don’t have to poke a needle in someone’s bone. You can just take a sample of their blood, and it tells you the same information,” Dr. Lucci said.
CTCs have been shown in breast cancer to rise and fall depending on tumor response. “In the future, I do think we will [use them] as a serial monitoring tool and a guide to therapy.” There might even be a role for breast cancer screening, he said.
Analyzing the blood for evidence of solid tumors – popularly called “liquid biopsy” – has shown benefits in a variety of cancers, particularly for identifying disease, and in some cases mutations, sooner than with conventional methods. Science is catching up to the old-school notion that cancer spreads through the blood.
Another approach is to look for circulating tumor DNA, which has been shown to be useful for early detection in gynecologic cancers. The idea is that a few tumor cells shatter and spill their genetic material into the blood early on. “In the majority of breast cancer patients,” however, “you don’t find actionable mutations” with circulating tumor DNA, especially in earlier-stage, nonmetastatic disease. “There’s not enough DNA released into the blood,” Dr. Lucci said.
But “we need to be monitoring the blood on a routine basis” for breast cancer clues. “That, I think, is the wave of the future. Just looking at x-rays and waiting for something to happen is too late,” he said.
Dr. Lucci had no disclosures related to his talk.