Breast Cancer Clues: Better Biopsies

Reported April 16, 2010

(Ivanhoe Newswire) -- Researchers say they have found clues to molecular markers on breast tumors that may predict which cancers will metastasize to the lymph node system.

Predicting breast cancer spread from a sentinel lymph node removed during surgery can be a hit or miss affair, and false negatives are a problem. When a node is analyzed under a microscope, even though it appears clean of cancer cells, metastasis can still occur in the patient. The sentinel node is the first lymph node in the axilla to which the cancer spreads.

In a pilot study comparing genomic alterations in both breast cancer cells and sentinel lymph nodes removed from 15 patients whose cancer had spread to the lymph nodes, researchers found genes that were altered in both samples. These alterations affected genes that function as either oncogenes or tumor suppressors. The goal is to be able to determine, when a patient has a routine biopsy of her tumor at the time of the diagnosis, who is at higher risk for developing lymph node metastasis, according to Luciane Cavalli, Ph.D., assistant professor of oncology at Lombardi.

"To our knowledge, very few studies have looked specifically for genomic alterations in sentinel nodes in comparison to the primary tumor from the same patient," Dr. Cavalli was quoted as saying. "If we find markers that can be significantly associated with patients who develop axillary metastasis, we can check for these markers at an early stage of the cancer management, before axillary lymph node metastasis develops. That will give physicians a chance to treat what is otherwise an unseen metastasis."

Currently, a sentinel lymph node is removed at the time the patient undergoes surgery to remove breast tumors, and the node is examined for evidence of cancer cells while the operation is in progress. If malignant cells are seen, additional nodes in the axilla are removed, explained Dr. Cavalli. "This procedure is performed during the surgery, and the methods currently used to look for tumor cells in these nodes are not ultra sensitive, and may therefore miss these malignant cells especially in the case of micrometastasis."

Dr. Cavalli and her team first screened the genomes of cells from both tumors and nodes from the same patient using comparative genome hybridization (CGH), and found that most of the genomic regions affected were similar in both of the samples. They used microarray technology (array-CGH) to identify the genes altered in these regions and found several that were altered in patient lymph nodes and tumors. Some of these genes are well known, such as the growth promoting gene her2neu, and the tumor suppressor BRCA1.

"It differed between patients -- in some, BRCA1 was missing in both samples, in others, her2neu or other genes were amplified," said Dr. Cavalli.

"If we can use these genomic markers to identify tumor cells in the sentinel lymph node to reduce the false negative rates that now exist in sentinel node biopsy,” said Dr. Cavalli, “we can advance one step forward in patient care."

SOURCE: Presented at the American Association for Cancer Research (AACR) Annual Meeting, April 18, 2010