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Breast Cancer Detection Made Easier

By Monday Paper
University of Cape Town, South Africa

April 24, 2005

One in ten women will die of breast cancer according to current statistics

One in ten women will die of breast cancer according to current statistics. While health and awareness campaigns have improved early detection rates of the disease, researchers like University of Cape Town's (UCT) Dr. Sahar Abdul-Rasool, of the clinical laboratory science department, are working on the clinical side to provide women with a more sensitive diagnostic test, one that allows for earlier intervention.

An Iraqi, Abdul-Rasool came to South Africa three years ago to begin her PhD in hematology at the university’s molecular biology laboratory.

Abdul-Rasool qualified with a bachelor’s degree in medicine and surgery from the University of Baghdad, College of Medicine in 1987 and obtained her master’s degree from Nahrain University Medical College in 1995, her thesis on the quantitative histochemical study of skeletal muscle fiber. She has also lectured at universities in Yemen and Libya.

Abdul-Rasool is part of a collaborative team of researchers from UCT's clinical laboratory sciences, surgery and anatomical pathology departments who are conducting an important study to develop a more sensitive diagnostic test for breast cancer that will provide earlier staging and testing.

According to the researcher, if diagnosis and treatment of breast cancer are delayed until the primary tumor has metastasized (spread) and the lymph nodes are palpable; the five-year survival rate for women is 45% to 50%.

Much of the current research into the disease concerns the sentinel lymph nodes in the cancerous breast tissue. A sentinel node is the first lymph node in the axilla (the armpit) to receive drainage from a cancer-containing area in the breast. This is what doctors try to remove, sparing the wholesale removal of tissue in the axilla (which contains fat, lymph nodes, lymph and blood vessels as well as nerves), to prevent any cancerous cells from spreading.

New insights have shown that wholesale removal of the axillary tissue does not necessarily prevent breast cancer from spreading. It also often causes numerous side effects like chronic pain and lymphedema (chronic swelling of the arm due to blockage of the lymph vessels).

Sentinel lymph node biopsy, however, provides doctors with a far more accurate way of isolating the cancer.

"It is the likely site for lymphogenic metastases [cancer cells spreading through the lymphatic vessels]," Abdul-Rasool explained. Sentinel lymph node biopsy involves a more delicate technique, and by lessening side effects in this way the procedure is less complicated for the patient in the short and long term, she said.

However, it is known that breast cancer patients with no clinically-apparent signs of metastases may already harbor nodal micro metastases; cancerous spread at a molecular level.

Staging involves histopathological examination of the sentinel node to detect cancerous spread to the surrounding or axillary nodes

"If you can detect and more accurately stage the cancer at this point, treatment is more likely to be effective as the tumor burden is small and the host is still immune-competent. Currently, staging involves histopathological examination of the sentinel node to detect cancerous spread to the surrounding or axillary nodes.

The sentinel node is the most likely site for spread among the lymph glands and can be identified with a 98 percent accuracy using radio-guided surgery.

"We're already using this surgical technique at Groote Schuur Hospital (GSH)," Abdul-Rasool added.

But the method of examining the sentinel node is still costly and labor-intensive. The team of researchers has now developed a specific and reproducible molecular assay that can accurately detect the spread of cancerous cells in the sentinel nodes.

The team evaluated the gene expression patterns of 73 molecular markers in sentinel node biopsy specimens gathered from patients at GSH.

Most of these are cancer-testis antigens (CTAs); antigens normally present in testis tissue but abnormally expressed by cancerous cells.

"Breast cancer has its own unique CTA profile and our aim was to find the perfect combination of markers to ensure 100 percent detection and specificity."

The results have been very encouraging. The researchers found that immunohistochemical analysis in the lab resulted in a 77 percent detection rate, compared with 37 percent for histopathological examination.

"Immunohistochemical analysis is considered essential in order not to miss sentinel node micrometastases. Molecular analysis of breast tissue with breast tumor markers MAM-A (mammaglobin-A) and MAGE-A3 (Melanoma antigen, family A, 3) were found to allow specific and sensitive detection of breast cancer micrometastases with a 90 percent detection rate.

"However, the clinical value of histologically negative but molecular positive sentinel nodes can only be determined with long-term follow-ups with patients.

"This work can revolutionize breast cancer diagnosis and staging, allowing for earlier treatment, better prognoses and prolonged patient survival."

Abdul-Rasool took her findings to Sydney where she presented her work at the prestigious Leura V International Breast Cancer Conference in November 2004.

Her supervisor, senior medical scientist Dr Gideon Hanekom, considers this asignificant achievement. It also vindicates Abdul-Rasool's initial thoughts about choosing to train at an institution in Africa's southern-most tip.

"UCT is a university with outstanding research capacity. Here I can fulfill my hopes and ambitions regarding my scientific work," she said.

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