Could surgery to remove breast cancer tumors actually increase the risk of a relapse?
A small group of respected researchers suspects that in a significant number of women, surgery itself may trigger the rapid growth of smaller tumors elsewhere in the body.
While many cancer experts are skeptical about the controversial theory, supporters say there is growing evidence for the idea.
"With [surgical] intervention, we may in some cases make things worse," says Michael Retsky, a researcher at Harvard Medical School and Children's Hospital in Boston.
Retsky argues that more than half of breast cancer relapses may be accelerated by surgery and says the phenomenon may apply to surgery for other types of cancer.
Proponents of the hypothesis emphasize that breast cancer patients should not reject or put off surgery. "I would not want to discourage women from having surgery because of a fear of spreading tumors," says Dr. Larry Norton, who nonetheless calls the hypothesis "intriguing."
The director of breast cancer research and treatment at Memorial Sloan-Kettering Cancer Center in New York, Norton is planning lab studies to examine the effects of surgery on secondary, unremoved tumors.
If breast cancer operations do turn out to stimulate tumors, researchers will have to develop techniques to counteract the effect, perhaps with drugs that blunt the body's response to surgery.
For decades, scientists have known surgery stimulates production of proteins and other chemicals to encourage healing.
Retsky and others argue that the process also appears to promote development of small breast cancer tumors scattered around the body -- growths that had been either dormant or slow-growing.
Known as metastases, these tumors occur in many cancers. Most are tiny, sometimes just a few cells.
"When you operate on someone, you trigger a cascade of genetic signals that lead to healing. These same signals are just what a dormant cancer needs to proliferate," says Dr. Michael Baum, a respected cancer surgeon and researcher at University College in London. He is one of the theory's most enthusiastic advocates.
The hypothesis ties into another hot area of cancer research. In recent years, scientists have focused on the idea that tumors need a surrounding network of blood vessels to grow and spread. Many cancers persuade the body to construct these networks, allowing the tumors to thrive.
Several recent blockbuster drugs, including Genentech's Avastin, work by shutting off the cancer's ability to create this complex of vessels.
Baum and others believe that surgery can also spur this blood vessel growth, which is known as angiogenesis. Ironically, they say, in ramping up the body's wound-healing machinery, an operation may also send growth signals and nutrients to tumors.
The phenomenon may have causes in addition to angiogenesis. Dr. Judah Folkman, a Harvard researcher famed for his work on angiogenesis, says that some large primary tumors may secrete substances to inhibit the growth of smaller secondary tumors.
"One tumor can suppress another one," Folkman says. "The large tumor controls the others." Once a large tumor is removed, this suppression wanes.
"The brakes are off," he says.
Experiments have shown that this process occurs in mice, and Folkman suspects it also takes place in humans, too. But no studies have been conducted.
The evidence for a surgical role in cancer growth is credible but not overwhelming. In a paper last year in the International Journal Of Surgery, Retsky and several colleagues mined data from a long-running study of 1,173 Italian women with breast cancer.
Retsky noted that deaths from cancer recurrence rose sharply two years after tumor removal, sooner than might otherwise be expected. He argued that the only plausible explanation for this early jump in mortality was the surgical stimulus given to the distant tumors.
And last year, researchers at the Indiana University School of Medicine in Indianapolis added some animal evidence when they surgically removed tumors from a group of mice with breast cancer. Six weeks later, almost three-quarters of the animals had significant breast cancer metastases in their lungs.
Dr. Susan E. Clare, the surgeon who led the study, notes that human physiology differs significantly from that of mice, but says the results should lead to further research in humans. "If this hypothesis is right, we could save a lot of lives," she says.
About 211,000 women were diagnosed with breast cancer last year in this country, and more than 40,000 died from the disease.
Retsky says his research indicates that surgery-induced tumor growth may occur in over half of those deaths. "Twenty-five thousand women a year die earlier than they otherwise would have," he says. "This is a huge effect."