Studies show that breast cancer metastasis (cancer that has spread from the site of the original tumor) sometimes occurs 12 to 18 months following surgery, says Robert Weinberg, PhD, the senior author of the new study, a professor of biology at the Massachusetts Institute of Technology in Cambridge, and a member of the Whitehead Institute, which is affiliated with MIT. “Given the fact that it spikes and then goes down, that means it’s highly likely to have been caused by the surgery. It settles down at a really low rate for several years after that spike,” says Dr. Weinberg. “No one knows why metastatic relapse is provoked. One theory is the surgery itself scatters cancer cells into the blood, which may then seed at distant sites and cause metastasis.” But Weinberg and his coauthors are proposing that a different mechanism may be at play — the effects of inflammation due to wound healing.
The Immune System Dealt a Blow by Cancer Surgery
Weinberg and his colleagues used a mouse model of breast cancer to explore the impact of wound healing on cancer metastasis. They found that in mice with a transplanted breast cancer tumor, natural immune-system defenses, such as T cells, kept the tumor cells in a dormant state in which they did not divide or spread. In mice with a transplanted breast cancer tumor that were healing from an induced injury, however, the tumors metastasized at a much higher rate. The findings suggest that inflammation that develops during the wound-healing process interferes with the immune system, preventing it from keeping tumor cells dormant and inactive. “What we propose is that some of these disseminated cells are kept under control by the immune system,” Weinberg says. “What we find is, in a model of postsurgical wound-healing, it’s not the surgery itself but the subsequent wound-healing response that can act throughout the body to suppress certain kinds of immunological functions. When these immunological functions are suppressed, these disseminated cancer cells that had been under control can sally forth and generate.” “It’s a very important paper,” says Michael Retsky, PhD, a research associate at the Harvard T.H. Chan School of Public Health who has studied breast cancer surgery and relapse. “Surgeons have claimed for a very long time that surgery doesn’t cause cancer to spread. The simple answer is that it does. While cancer is a cellular disease, we are finding that most distant relapses in breast and probably other cancers result from systemic inflammation.” RELATED: When Breast Cancer Spreads: What to Expect
Something as Simple as an NSAID Reverses the Effect
One prior research study suggests that administering nonsteroidal anti-inflammatory drugs (NSAIDs) instead of opioids for pain relief following breast cancer surgery may reduce the risk of a cancer recurrence. As part of the experiment, the researchers gave the wounded mice the NSAID meloxicam. The mice that received meloxicam developed much smaller metastatic tumors compared with the untreated wounded mice. Giving breast cancer patients NSAIDs post-surgery could be a simple and helpful strategy to prevent cancer recurrence, Weinberg says. “Our paper is there to provoke the research community to examine this mechanism to see if it can be validated in women and might affect clinical practice,” Weinberg says. “A mouse is not a human, but there are similar mechanisms that seem to govern how the immune system functions.” Dr. Retsky is seeking funding to conduct a clinical trial using the NSAID ketorolac on surgical breast cancer patients in Nigeria where there are few resources to catch cancer early. Nigerian women also have high rates of a particularly dangerous form of breast cancer called triple-negative breast cancer. NSAIDs can be given safely to surgical patients, Weinberg says. “It depends on the dose of NSAIDs. In our mouse system, the NSAIDs did not have a negative effect on wound healing. NSAIDs have to be applied with caution. They can result in some bleeding, but it depends on what dose they are given in.” More study is needed to determine if the same mechanism may apply to surgery for other types of cancers, says Weinberg.
