Breast surgery gets blame for induced angiogenesis

The merits of screening mammography are yet again being debated in the U.S., thanks to research suggesting that breast cancer surgery speeds up disease progression in young women. The study's authors are recommending that the risk of accelerated tumor growth and early relapse be included on breast screening consent forms.

This latest claim, published online in the International Journal of Surgery [doi:10.1016/j.ijsu.2005.08.002], is based on data from 1173 women who underwent mastectomy alone as treatment for breast cancer at the Milan Cancer Institute between 1964 and 1980. On examining the historic data, researchers noted a significant relapse peak eight to 10 months after surgery. The peak affected 20% of premenopausal patients with node-positive disease. A second, broader relapse peak across the group occurred after five years.

The team posits that the first peak's surprising sharpness is due to a sudden awakening of dormant cancer cells. In other words, the surgical treatment had induced angiogenesis. They support the theory with additional calculations that show their model fits mortality figures and relapse patterns in screening trial data.

"We originally thought that the two different peaks represented two different states of tumors - one dormant and one growing," said lead author Michael Retsky, Ph.D., an investigator in the vascular biology program at Children's Hospital Boston. "The surprise to us was that the first peak represented patients who actually had their cancers accelerated by surgery."

Options for testing the hypothesis include further data analysis and clinical trials into the impact of anti-angiogenic drugs or hormone-based therapy when performing breast surgery, Retsky said.

"If what we say is correct, then there should be ways of intervening around the time of surgery to prevent this induced angiogenesis," he said.

The new theory is likely to revive discussion of an apparent paradox: Women aged 40 to 49 who undergo breast cancer screening increase their risk of dying from the disease. At the very least, young women should be informed of the phenomenon when signing an informed consent form, Retsky said. But the notion that the young women may do themselves more harm than good by undergoing screening mammography remains hotly contested.

"This is just one in a series of myths about screening women in their 40s that have been promulgated over the years," said Dr. Daniel Kopans, director of breast imaging at Massachusetts General Hospital. "The apparent 'paradox' is the result of a failure to understand randomized control trials and misinterpretation of the data."

There is no reason to believe that breast tumor removal promotes metastatic cancer growth, according to Kopans. While this does occur for some tumors in certain animal models, it is a transient, short-lived phenomenon, and mortality is not accelerated.

While invasive breast cancer has been observed to grow more quickly in very young women than in older women, this is more likely due to a straightforward model of breast cancer growth than surgery, Kopans said. So women in the Milan study group who relapsed early simply died from their preexisting metastatic disease.

Kopans is adamant that women in the 40 to 49 age group should have no qualms about screening mammography.

"The data clearly show that screening saves lives among women who begin screening by the age of 40," he said. "I would challenge anyone who suggests that the age of 50 is anything but an arbitrary threshold to provide ungrouped data to support that contention."

For more information from the Diagnostic Imaging archives:

Is 'mortality paradox' real or chance finding?

Digital mammography finds more cancers than film in women under 50

Mammographically detected tumors display better survival prognosis

Study questions gains in 'real world' breast cancer screening