Surgery May Unleash Breast Cancer Growth
By Daniel J. DeNoon
Can removing a breast cancer cause rapid growth of tumors elsewhere in the body?
Yes, according to indirect evidence from a new analysis of clinical trial data. The controversial theory comes from Michael Retsky, PhD, of Children’s Hospital/Harvard Medical School in Boston, and colleagues.
“We say this is indirect evidence; we think this is a key to understanding the biology of breast cancer,” Retsky tells WebMD. “We certainly do not suggest any changes in clinical practice based on this. We hope this will entice clinical and experimental people to test these hypotheses.”
However, the theory is extremely controversial. A spokesman for the American Cancer Society says the findings are based on a misreading of existing data.
Big Tumors Fighting Little Tumors
Retsky and colleagues looked at long-term data on breast cancer patients treated in Italy. They saw two peaks in breast cancer relapse among premenopausal women whose cancer had spread to their lymph nodes. One relapse peak came very early — just 18 months after cancer diagnosis. The other started nearly five years after diagnosis.
This led them to a hypothesis. Cancers that relapse five or more years after cancer surgery, they suggest, come from single cancer cells in the body that grow slowly over time. Early relapses, they suggest, come from tiny, dormant cancers about 1 millimeter in size.
What makes these tiny cancers grow?
Animal studies show that big tumors give off chemical signals that keep smaller cancers from growing. When these big tumors are removed, the smaller cancers quickly grow blood vessels and become deadly.
The same thing may happen in some women after breast cancer surgery, Retsky says. And it’s seen only in younger women, he suggests, because reproductive hormones boost the cancer-enhancing effect.
Breast Cancer Screening Paradox
For more evidence, Retsky’s team looked at what some call the breast cancer screening paradox. It comes from observations in clinical trials comparing regular mammogram screening with no screening. In the first few years, women in their 40s who have mammograms — but not those in their 50s — have a higher risk of death than those not offered screening.
Over time, breast cancer screening shows a benefit for all women. But why the early increase in risk? Could it be due to women with node-positive breast cancer who suffer early relapses after surgery? Retsky suggests that it is.
Looking at data from studies of breast cancer screening, Retsky and colleagues saw about one excess death per 10,000 screened young women in the third year of screening. That, he says, is just what one would expect if his hypothesis is correct.
“It looked like surgery accelerated the disease by two years on average, which is the usual dormancy of this [blood vessel-free] tumor state,” Retsky says. “All the data show this.”
Even so, Retsky stresses, younger women with breast cancer still need surgery. He strongly advises women to continue to seek breast cancer screening — and, when a cancer is found, to have it removed.
“We don’t have all the answers,” Retsky says. “We think our work has pointed out that the mammography paradox is real. We are confident we understand what causes it. We have identified a problem — a mechanism that is testable. We have not found a solution. But identifying the problem is a major step in the right direction.”
Retsky and colleagues report their findings in the current issue of the International Journal of Surgery.
American Cancer Society Says It Isn’t So
Don’t believe any of this, says Robert A. Smith, PhD, director of cancer screening for the American Cancer Society.
“The data don’t add up to Dr. Retsky’s conclusion,” Smith tells WebMD. “The idea that surgical interruption of the tumor bed will cause death this rapidly just does not make sense.”
Smith, a strong proponent of early and regular breast cancer screening, says the apparent screening paradox does not exist.
“You do not expect mammograms to be instantly beneficial,” he says. “When you first invite women to screening, you get some with tumors that are already advanced. And not all of the women will respond to the invitation to screening. They may die next year or the year after, and because they were invited, they will be counted as a death in the screening group. So you really can’t look at this pattern and make any sense out of it.”
Young women, Smith says, tend to get more aggressive breast cancers.
“So the idea these women became worse after surgery may stem from the fact that their prognosis may have been poorer to begin with,” he says.
And Smith notes that Retsky’s data are based on observations from long ago, when breast cancer screening was in its infancy.
“The interesting thing is how beneficial modern, high-quality mammography can be,” he says. “Mammograms are quite a bit better today than in the clinical trials that proved they saved lives.”
SOURCES: Retsky, M.W. International Journal of Surgery, published online, Sept. 12, 2005. Michael Retsky, PhD, Children’s Hospital/Harvard Medical School, Boston. Robert A. Smith, PhD, director of cancer screening, American Cancer Society.