Doctors have long wondered why breast cancer patients are more likely to see their cancer spread within the first 18 months after a lumpectomy or mastectomy.
A new study suggests the wound healing that follows surgery may trigger this spread.
As the immune system works to heal the surgical scar, it stops restraining cancer cells that have wandered far from the tumor site, according to the study published Wednesday in Science Translational Medicine. Without this brake, those cancer cells are free to grow and become new, more dangerous tumors.
“It's not the actual surgery, but instead, it's the post-surgical wound response,” said Robert Weinberg, the paper’s senior author and a biologist at the Massachusetts Institute of Technology. “It is provoking already disseminated cells to begin to grow into clinically detectable metastases.”
The same study suggests there may be a simple solution: taking an anti-inflammatory drug.
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A few days of anti-inflammatory therapy kept the immune brake engaged in mice and prevented spread, according to the study. Research in people hinted at the same benefit, although more studies are needed to confirm it.
Michael Retsky, an oncology researcher at the Harvard T.H. Chan School of Public Health and University College London, said his own research in people isn’t definitive, but it has convinced him that the benefits are probably real.
In one small study, he showed that breast cancer patients who got the anti-inflammatory drug ketorolac for a few days around the time of surgery were five times less likely to have their cancer spread than people who didn’t get the prescription medication.
Sometimes surgeons don’t like to give anti-inflammatory medications during and after surgery because they can lead to bleeding problems — although those can largely be controlled, Retsky said.
Retsky hopes trials will begin soon in Nigeria to test the benefits of adding ketorolac, which is often used in lieu of opioid painkillers, to the surgical process.
That such drugs "might have an effect on cancer or cancer spread mediated on its effect on immune cells is very intriguing,” said Andrew Chan, a gastroenterologist who studies the relationship between cancer and aspirin.
Chan’s own research suggests that, in general, aspirin provides more anti-cancer benefit than other drugs in the same category, called non-steroidal anti-inflammatory drugs or NSAIDS. He’s not sure whether there would be any differences at the time of surgery. In animal models, he said, other NSAIDS seem to be more effective than aspirin at fighting cancer, but in people, aspirin seems to do better.
Studies are testing to see whether aspirin can cut down on cancer recurrence, but they are focused on long-term recurrence, not the first year after surgery, said Chan, a professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, both in Boston.
Almost everyone who dies from breast cancer is killed not by the initial tumor but by its spread to other areas of the body, noted Weinberg, who is affiliated with the Whitehead Institute for Biomedical Research in Cambridge, Mass. He has spent the past several decades trying to understand how that spread occurs. The immune system’s control on spreading cells is just one mechanism, he said. He continues to search for and study others.
To close an open wound, the immune system must trigger cells to move to new locations and divide and blood vessels to grow, said Hanna Dillekås, an oncologist at Haukeland University Hospital and a researcher at the University of Bergen, both in Bergen, Norway. This is precisely what goes on when cancers spread, she said, so the new study makes perfect sense to her.
“The pieces fit really well together — what we see in humans and what they have demonstrated in mice,” Dillekås said.
Although the data are not definitive in people, Dillekås said that if she got cancer surgery, she’d ask for an anti-inflammatory drug.
"I would definitely go for it,” she said.
PHOTO: U.S. Air Force photo/Airman 1st Class Andrew Lee