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Revised classification system is effective for predicting breast cancer outcome in some patients

University of North Carolina Health Care

CHAPEL HILL -- A revised and commonly used system for classifying the seriousness of cancer is effective for predicting relapse and survival in women with breast cancer who receive chemotherapy prior to surgery, according to research from the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center.

The findings may provide information that will help doctors shape subsequent treatment, researchers said.

The new study, appearing today (Aug. 3) in the Journal of the National Cancer Institute, is the first to examine the ability of the revised (2003) American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system to predict breast cancer outcome after neoadjuvant chemotherapy.

"Neoadjuvant" refers to treatment given to help the subsequent primary treatment proceed more successfully.

This type of therapy is being used increasingly in breast cancer while the tumor is still in place. Typically used for locally advanced breast cancer, or tumors three centimeters or larger in diameter, neoadjuvant chemotherapy may shrink malignancies, making them easier to remove surgically, said Dr. Lisa Carey, associate professor of medicine in the UNC School of Medicine's Division of Hematology/Oncology and the report's lead author.

"You can actually measure the response of the tumor to the chemotherapy, and we have found it may improve the likelihood of having a lumpectomy instead of mastectomy," she added.

Carey, also a member of UNC Lineberger, said the amount of residual tumor remaining after the chemotherapy has important implications for survival.

"A woman whose tumor is obliterated, where none remains after the chemotherapy, has a better outcome five years later than a woman who still has cancer left in the breast."

However, debate has focused on the best way to measure that residual amount, Carey added.

"So our study looked at the revised AJCC TNM classification system to determine if it was helpful for predicting outcome. And using the same data set, we also compared the system with several other classification methods that have been used in clinical trials."

The TNM system was developed as a tool for doctors to stage different types of cancer based on certain standard criteria. In breast cancer, it is based on the extent of the tumor in the breast, the extent of spread to axillary (armpit) lymph nodes, and the presence of metastasis. The "T" category describes the original, or primary, tumor.

Once the criteria are determined, they are combined, and an overall "stage" of I, II, III or IV is assigned. Sometimes these stages are subdivided as well, using letters such as IIIA and IIIB. In general, the lower the number, the less the cancer has spread. A higher number means a more serious cancer. Stage I cancers are the least advanced and often have a better prognosis, or outlook for survival. Higher stage cancers are often more advanced, but in many cases can still be treated successfully, according to the American Cancer Society.

The UNC study included 132 patients with locally advanced breast cancer who had been diagnosed with clinical stage II or III disease, according to the 1988 AJCC TNM system. All had been treated at UNC in neoadjuvant chemotherapy clinical trials followed by surgery from January 1992 through December 2000.

Using surgical tissue samples from each patient's breast and axillary lymph nodes, the researchers measured the pathologic, or disease, stage of the patients' residual tumor with the revised AJCC TNM staging system. They then looked at the association between tumor stage in the surgical specimens and five-year disease outcome.

After a median of five years, residual tumor stage as measured by the revised TNM was strongly associated with both distant disease-free survival and overall survival, the report said. A higher stage of residual tumor after neoadjuvant chemotherapy was associated with a statistically significant lower rate of disease-free survival.

"Before the revisions, the AJCC system didn't take into account the number of nodes that had cancer left in them very well," Carey said. "It didn't emphasize the difference in prognosis between a person with one lymph with cancer and women who have 10 lymph nodes with cancer.

"There were other changes to the system, but that was the most relevant for our study. The new system has been widely adopted, and now we know that it can give us very useful information about how to assess the response to neoadjuvant chemotherapy."

Funding for the study came from a UNC Breast Cancer SPORE Award from the National Cancer Institute, the Breast Cancer Research Foundation and the National Institutes of Health.

Carey's UNC co-authors include Dr. Richard Metzger, research assistant; Dr. E. Claire Dees, assistant professor of medicine; Dr. Frances Collichio, assistant professor of medicine; Dr. Jan S. Halle, associate professor of radiation oncology; Dr. Carolyn Sartor, assistant professor of radiation oncology; Dr. David Ollila, associate professor of surgical oncology; Dr. Nancy Klauber-Demore, assistant professor of surgical oncology; Dr. Dominic T. Moore, biostatistician; Lynda Sawyer, research assistant; and Dr. Mark Graham, now in private practice, formerly at UNC.

UNC Lineberger is one of 39 National Cancer Institute-designated Comprehensive Cancer Centers and two Specialized Programs of Research Excellence (SPORE) in breast cancer and in gastrointestinal cancers.


Note: Contact Carey at 919-966-4431 or
UNC Lineberger contact: Dianne Shaw, 919-966-7834 or
School of Medicine contact: Les Lang, 919-843-9687 or

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