New test can better uncover hidden breast cancer

September 10, 1999

Study by USC Scientists and Colleagues Points to Better Detection, Treatment

A new test appears to discover hidden cancer cells in women with breast cancer more effectively than current detection methods, better indicating which women need aggressive anti-cancer treatments and which can be spared the side effects of chemotherapy, according to a study by scientists at USC/Norris Cancer Center and the International Breast Cancer Study Group.

The findings, published in the Sept. 11 issue of The Lancet, point the way to more advanced, customized treatments suited to meeting the medical needs of individuals with breast cancer. Doctors may be able to gather information about the characteristics and extent of a patient's cancer far better than ever before.

"Our findings may help to identify those patients with breast cancer who are at greatest risk of developing metastases, and who thus need treatment beyond surgery, particularly chemotherapy. The findings may also be used to help identify those women with breast cancer who can be spared the side effects and expense of chemotherapy," said Richard Cote, M.D., professor of pathology at the University of Southern California's Keck School of Medicine, who authored the paper with colleagues at USC and the International Breast Cancer Study Group. The group includes investigators from the Ludwig Institute for Cancer Research, Harvard University and cancer institutes in Europe, Australia and New Zealand.

According to the American Cancer Society, about 180,000 new cases of the breast cancer are diagnosed and about 44,000 women die from it annually in the United States.

During most breast cancer surgeries, surgeons remove several lymph nodes, called axillary nodes, to see if the cancer has spread, or metastasized, beyond the original tumor in the breast. The presence of cancerous cells in the lymph nodes indicates that the tumor has metastasized. But under the current way of examining those lymph nodes (slicing the nodes and staining them with two dyes called haematoxylin and eosin) about 25 percent of patients who show no sign of cancer in the nodes end up developing cancer in other places in their bodies.

In current methods, pathologists look for cancer in slices of lymph nodes that have been stained and magnified under the microscope. They can spot cancer cells by looking at the shape of cells and the way they are clustered. While this technique is sensitive and reliable, if cancer cells do not have a typical shape or architecture or if there are very few such cells in a lymph node, the cancer might go unnoticed.

The new test significantly improves on the standard methods to detect cancer in the lymph nodes. It requires a mix of two substances, called antibodies. "These antibodies detect, with a high degree of accuracy, proteins that are present in breast cancer cells, but not present in the normal cells of the lymph node," Cote said. The antibodies are placed on the lymph node tissue, and if breast cancer cells are present, they will react with the antibodies - - producing a color change in the cancer cells that a pathologist can detect under the microscope. Even very small numbers of cancer cells, which usually are extremely difficult to identify by conventional methods, can be detected through this new technique.

To study the effectiveness of the new procedure, scientists examined lymph node tissue from 738 breast cancer patients. These patients were considered to have no evidence of metastases in their lymph nodes by conventional analysis. The lymph nodes were then tested with the antibody mixture to look for signs of occult, or hidden, cancer. Scientists found occult nodal metastases in 20 percent of the patients using the antibody technique. Occult metastases were more commonly found in lymph nodes from women with large breast cancer tumors, which have a higher risk of developing metastases. However, in some cases, metastases were even found in patients who had small tumors in the breast.

On a long-term basis, the study found that the presence of occult cancer metastases in the axillary lymph nodes detected by the antibody technique identified women with a greater chance of developing overt metastases and dying of breast cancer. This effect was strongest in older (post-menopausal) women, the group with the highest incidence of breast cancer. However, in younger (pre-menopausal) women with breast cancer, the presence of occult lymph node metastases did not appear to have a significant effect on overt metastases or survival.

Scientists said the findings indicate cancers may spread differently in older women. Further study is needed to understand the differences in breast cancer spread and behavior between older women and younger women.

The study findings point to better ways to treat each cancer patient individually, Cote said, based on the specific characteristics of their cancer. Finding occult metastases in the lymph nodes would be one factor. Cote and colleagues also have found that occult metastases can be detected in the bone marrow of patients who otherwise have no evidence of metastases by conventional methods. Combined with other information, such as age, the presence of hormone receptors in a cancer cell, and the status of other genes and proteins known to be important in breast cancer treatment such as HER2/neu proteins, therapies can be tailored to fit the needs of each individual patient. Currently, a general recipe of surgery, radiation and chemotherapy is considered for everyone with early stage breast cancer.

"Once you get this information, you get a better idea of the nature of the tumor," Cote said. "The ability to identify those patients who need treatment, and the specific type of treatment that would most benefit the patient, would certainly represent a major advance in the management of breast cancer."

Additionally, some women who ordinarily would receive chemotherapy might even be able to avoid the uncomfortable, costly and potentially risky process because it is unnecessary for them, Cote said.

Cote said the antibody detection method holds promise for other types of cancer as well, including melanomas, colon carcinoma, non-small-cell lung carcinoma and esophageal carcinoma. The new testing technique is already in use at the USC/Norris Cancer Center and Hospital.
EDITOR: See R.J. Cote, H.F. Peterson, B. Chalwun, R.D. Gelber, A. Goldirsch, M. Castiglione-Gertsch, B. Gusterson and A.M. Neville, "The role of immunohistochemical detection of lymph-node metastases in management of breast cancer," Lancet, vol. 354, mo. 9182, pp. 896-900.

University of Southern California

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