Breast cancer typically spreads first to the underarm lymph nodes. In the study, published in the British journal The Lancet ( Vol. 354, No. 9182), researchers re-examined lymph node specimens from 736 breast cancer patients that were classified as disease-free by a routine detection method. Using the first new method, serial sectioning, researchers found the cancer had spread to the lymph nodes in seven percent of the patients, while another new detection method, immunohistochemical staining for cytokeratins, detected spread to lymph nodes in 20 percent of the patients.

The routine method examined a few slices of each lymph node under a microscope. For the serial sectioning method, the researchers examined 12 slices, thereby increasing the odds of finding small tumor deposits that were missed by the routine method. The immunohistochemical method used special antibodies to identify cytokeratins – a type of protein found in breast cancer and normal breast tissue but not in lymph nodes. This method causes cells containing cytokeratins to change color so that even very tiny tumor deposits can be recognized.

The researchers concluded the immunohistochemical method is a reliable, valuable, and simple way to detect hidden breast cancer cells in lymph nodes. "While our routine methods are good, they are insensitive compared to the immunohistochemical method," said Richard Cote, MD, lead author of the study and professor of pathology at the University of Southern California Medical School and the Norris Comprehensive Cancer Center in Los Angeles. "[The] immunohistochemical method allows us to see metastases long before we can see them by routine analysis. The test distinguishes breast cancer cells from normal cells of the lymph nodes and it specifically marks the cells so that we can see the breast cancer cells when they are low in number or when they look like cells that are normal in the lymph nodes."

Most importantly, finding very small tumor deposits, called micrometastases, in lymph nodes by serial sectioning or immunohistochemistry can help predict the risk of a patient's cancer recurring and may be useful in selecting treatments.

"Currently, we cannot tell the difference between high- and low-risk patients for disease progression," Dr. Cote added. "This test allows us to specify our treatment to these patients while giving us one more very important piece of information to understand the behavior of the tumor in the individual patient."

However, Cynthia Cohen, MD, director of immunohistochemistry at Emory University School of Medicine in Atlanta, said more large studies need to be done before the method could be considered the standard of care. "There is no doubt immunohistochemistry will pick up more cases with [cancerous] cells in the lymph nodes. The big issue is whether this makes a difference to patients," she said. "It's not going to be something we do all the time because it's not been proven in enough studies to be of significance."