Some women in their 40s who undergo surgery to treat breast cancer may actually increase their risk of a near-term relapse, according to a controversial Harvard Medical School study that suggests cancer surgery itself may "awaken" dormant tumor cells in other parts of the body.
The Harvard researchers found that, for about 20 percent of women in their 40s whose breast cancer has spread to their lymph nodes, cancer surgery seems to cause tiny tumors in other parts of their body to grow. Roughly 1 in 10,000 of these women would die early as a result. But the heightened risk of relapse was not seen in women 50 and older, and it seems to largely disappear for younger women after 18 months.
The researchers believe that their study, based on a computer analysis of past cancer cases rather than laboratory work, could mark the beginning of a new way of understanding why cancer spreads.
"Our results suggest most young women benefit from early detection of breast cancer, but a small percentage will relapse and die early of metastatic disease," said Dr. Michael Retsky, lead author of the study. He said there may be treatments to make surgery safer for the minority of women who are at highest risk of relapse, but "young women need to be advised of the risk of accelerated tumor growth and early relapse before giving informed consent for mammography" since surgical removal is a common treatment for tumors detected by the mammogram.
The study, published in this week's International Journal of Surgery, is likely to fuel the already-heated debate over the life-saving value of early detection of breast cancer. Monday, advocates of mammograms for women as young as 40 called the new study seriously flawed, and said it threatens to undermine a 25 percent drop in breast cancer death rates over the past 15 years.
"If we discourage women from getting breast cancer screening, significant gains that we have made will go down the tubes," said Dr. Daniel Kopans, a radiologist at Massachusetts General Hospital who has been a leading advocate for early breast cancer screening.
Dr. Patrick Borgen, chief of the breast service in the surgery department of Memorial Sloan-Kettering Cancer Center in New York, said the Harvard study is mostly "theory and hypothesis" that could scare people from getting mammograms out of fear that the treatment will kill them.
Retsky, who works in the laboratory of cancer research pioneer Dr. Judah Folkman at Children's Hospital Boston, based his findings on the long-term fate of 1,173 breast cancer patients who underwent surgery in Italy before 1980, when most patients started receiving chemotherapy after surgery to reduce the risk of cancer relapse. As a result, the researchers could focus on how the body responds to surgery alone. However, they argue their findings apply also to women who get chemotherapy, noting that recent studies show that women in their 40s don't get as much life-saving benefit from breast cancer treatment as older women.
The researchers found that more than one-quarter of premenopausal women whose lymph nodes tested positive for cancer suffered a relapse of cancer in the first 10 months after surgery. By comparison, women over 50 whose lymph nodes tested positive for cancer had a relapse rate of only 12 to 18 percent. The Harvard team, working with researchers from the Italian National Cancer Institute, concluded that the younger women whose cancers had already spread were at greater risk because removal of the breast cancer triggers chemical changes in their bodies that signal cancer cells elsewhere to form blood vessels so that they can grow.
Retsky said the theory helps to explain what he calls the "mammography paradox" in which women in their 40s don't benefit as much from cancer detection as older women. For example, a large-scale 2002 Canadian study showed that women in their 40s who received annual mammograms don't have a better chance of surviving breast cancer than women of the same age who skipped the mammogram.