Pharma Business Week , 24 March 2008
Breast Cancer; Test can reduce recurrence of breast cancer
2008 MAR 24 - (NewsRx.com) -- A new test that examines large sections of the sentinel lymph node for genes expressed by breast cancer could reduce the risk of recurrence and multiple surgeries, doctors say (see also Breast Cancer).
The GeneSearch Breast Lymph Node Assay, manufactured by Veridex, L.L.C., a Johnson & Johnson company, is being used at the Medical College of Georgia to examine half of the tissue in the sentinel lymph node, the first place breast cancer typically spreads. The sample represents more than 10 times the amount of tissue examined in traditional biopsies.
And because the test examines the tissue with molecular tools, it is more sensitive, says Dr. Zixuan (Zoe) Wang, molecular biologist and scientific director of MCG's Georgia Esoteric and Molecular Diagnostic Labs, L.L.C.
"When we look at the tissue with the GeneSearch test, we are looking for excessive amounts of mamoglobin and cytokeratin 19, both genes that are expressed more in breast cancer tissue," Dr. Wang says. "If those genes are present in excessive amounts, we know the cancer has metastasized."
MCG is the first place in Georgia to offer the test, which Time Magazine named one of the top-10 medical breakthroughs of 2007.
Done during a lumpectomy, the GeneSearch test uses molecular diagnostic methods to examine more tissue than traditional sentinel node biopsies, reducing the chance of false negative results, says Dr. Stephen Peiper, chair of the MCG Department of Pathology and Georgia Cancer Coalition Distinguished Cancer Clinician and Scientist.
The sentinel node, located in the armpit, filters fluid from the breast.
"During a traditional sentinel node biopsy, a surgeon would remove a node, then the pathologist would cut that section in half and cut that section to a quarter of the original sample size," Dr. Peiper says. "They then would cut wafer-thin slices from those sections, freeze and stain them, and look for cancer cells under a microscope. This technique, called frozen section, would be done during the lumpectomy surgery. If the tissue is positive for cancer cells, the surgeon removes more nodes from the patient, but if it is negative, the surgery is over."
The problem with that type of test, he says, can come when pathologists review more tissue slices during a confirmatory second test, called a permanent section and done a day later.
Permanent section tests are done the day after surgery because the tissue is set with a fixative that causes proteins in cells to harden for better examination.
"The cancer cells may not have been present in the part of the node that we looked at the day before in the frozen section," Dr. Peiper says. "But on the second day, we may find them in the other section. We perform both the traditional test and the new GeneSearch molecular test in parallel to provide the best care for our patients."
The larger the sample, he says, the better the chance of catching the cancer during the intraoperative test.
"If there are small amount s of cancer cells in the whole node, we may or may not see those with the traditional tests, because we only examine a small section of tissue," he says. "With this technology, we increase the chance of detecting them."
Nearly 20 percent of women with negative nodes confirmed by a traditional biopsy end up having a recurrence and metastasis, Dr. Peiper says.
"There is a higher false-negative rate with traditional sentinel node biopsies," says Dr. Scott Lind, professor and chief of the MCG Section of Surgical Oncology. "If that happens, the patient has to come back in for another surgery to take out more lymph nodes that have likely harbored the breast cancer cells."
In clinical trials, the new test correctly identified more than 95 percent of patients whose cancer had spread to their lymph nodes, according to Veridex, L.L.C.
"This will help us provide better care to patients and better overall treatment," Dr. Lind says.Pharma Business Week, 24 March 2008
Breast Cancer; Weill Cornell team identifies potential new drug targets against hormone-dependent breast cancer
2008 MAR 24 - (NewsRx.com) -- NEW YORK (Feb. 27, 2008) -- The identification of two cellular receptors that likely contribute to the genesis of hormone-dependent breast cancer points the way to new, highly targeted therapies against the disease, says a team led by scientists at Weill Cornell Medical College in New York City (see also Breast Cancer).
The finding also helps explain how daily use of medicines such as aspirin might help keep these breast tumors at bay.
"These two receptors, called EP2 and EP4, form key links in a biochemical pathway that boosts estrogen production in fat and breast cancer cells -- this, in turn, may increase a woman's risk for developing hormone receptor-positive breast cancer. Finding ways to interrupt this pathway in a manner that causes few side effects is the ultimate goal of this research," explains the study's senior author Dr. Andrew Dannenberg, director of the newly established Cancer Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and the Henry R. Erle, M.D.–Roberts Family Professor of Medicine at Weill Cornell Medical College.
The new findings were published recently in the online edition of the Journal of Biological Chemistry.
About 75 percent of all breast malignancies are "estrogen receptor-positive," meaning that their cells carry receptors attuned to estrogen. In the presence of the hormone, these cancer cells will divide and grow. For this reason, anti-estrogen drugs such as tamoxifen and aromatase inhibitors have come to the forefront in the fight against hormone-dependent breast cancer.
"Aromatase, an enzyme, boosts the amount of estrogen made by both fat cells and breast cancer cells," explains the study's lead author, Dr. Kotha Subbaramaiah, recently appointed the Jack Fishman Associate Professor of Cancer Prevention at Weill Cornell. "Cancer researchers have for years been exploring the pathway by which aromatase is regulated. We know that if you reduce aromatase activity that you also reduce levels of cancer-causing estrogen in breast tissues."
In 2006, researchers led by Dr. Dannenberg discovered that cyclooxygenase (COX) protein-derived prostaglandin E2 (PGE2) could turn on the gene that expresses aromatase. More recently, the healthy form of the BRCA1 tumor-suppressor gene was found to quiet the aromatase gene -- performing its duty in keeping breast cancer risk low.
"Maintaining this BRCA1-aromatase relationship in a healthy balance may help to keep patients free of hormone-dependent breast cancer," Dr. Dannenberg explains.
Studies have shown that use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) can also dampen PGE2 production and aromatase activity. COX-2 inhibitors (which include Vioxx and Celebrex) may do the same. However, these drugs also suppress a prostanoid that helps protect the heart, and in 2004 Vioxx was withdrawn from the market due to an excess of cardiovascular events noted in long-term users.
"So, we are always looking for other points in the prostaglandin -- aromatase -- estrogen pathway that can shield women from breast cancer without raising risks in other areas," Dr. Dannenberg says.
That's one of the reasons the results of the new study are intriguing. Using experiments conducted in cell culture and in the mammary tissues of mice, the Weill Cornell team discovered that two cellular receptors -- EP2 and EP4 -- switch on a complex biochemical pathway that activates the aromatase gene.
"It appears that PGE2 binds to these receptors and that this causes a downregulation of BRCA1," Dr. Subbaramaiah says. "As we already know, less BRCA1 means more aromatase activity to produce estrogen, and that could mean a higher risk for estrogen-receptor positive cancer."
The team found that EP2 and EP4 performed in this way in both adipocytes (fat cells) and in breast cancer cells. This could be important for both the development and growth of breast cancer.
"We also validated the presence of this pathway in an animal model, the first time that's ever been done," Dr. Dannenberg notes.
The finding has many implications going forward. First of all, it adds valuable new information to the study of hormone-dependent breast cancer generally. "Pinpointing the role of these receptors is like adding two important new parts to the tumor's 'instruction kit.' You have to understand all the players involved if you hope to uncover weaknesses to fight or prevent the disease," Dr. Dannenberg says.
Finally, the receptors offer brand new targets for pharmaceutical research. "In fact, drugs that work against EP2 and EP4 ('antagonists') are already in development by pharmaceutical companies," Dr. Subbaramaiah says. "Our confirmation of the receptors' key role in regulating aromatase activity supports the further development of this form of targeted therapy."
This article was prepared by Pharma Business Week editors from staff and other reports. Copyright 2008, Pharma Business Week via NewsRx.com.