New tests for Lung Cancer

The latest advance in personalized medicine promises to benefit thousands of lung-cancer patients. Under the current standard of treatment, people in the early stages of lung cancer undergo surgery to remove the tumor, followed by observation. Chemotherapy isn’t offered, nor covered by most health insurers. Yet, for a third of these people, the disease will return and is fatal.

Now, Duke University medical researchers say they have devised a test that predicts, with up to 90% certainty, which early-stage patients would suffer a recurrence. Those patients could then be given chemotherapy. In a study published in New England Journal of Medicine, the researchers say that the test, involving microscopic examination of thousands of individual genes, could save lives by bringing chemotherapy to patients who are currently advised against it.

Later this year, Duke will begin a clinical trial, funded by the NIH, of 1,200 early-stage lung-cancer patients in the United States and Canada.

The researchers’ findings herald the significant shift in cancer treatment known as personalized medicine, in which doctors tailor treatment to the genetic characteristics of each person’s cancer.

Joan Schiller, chief of the division of hematology oncology at University of Texas Southwestern Medical Center in Dallas, and the president of the National Lung Cancer Partnership, an advocacy group founded by physicians and researchers, called the Duke findings “a sign that we may be getting closer to personalized medicine where we look at a tumor and based on the molecular characteristics decide upon patients’ treatment.” She isn’t connected to the Duke study.

Assessing Breast Cancer Risk

Breast cancer strikes one in eight women. Mammograms or manual breast exams can find a tumor while it is still small and chances of survival are greatest. The new device aims to take early diagnosis one step further: predicting elevated risk before cancer even exists.

The “Halo system” device, which recently went on sale to gynecologists from NeoMatrix LLC of Irvine, Calif., is intended for use in addition to regular mammograms. The device works by extracting fluid from the nipple, using a warming technique and small suction cups. The fluid, called nipple aspirate, is then sent to a laboratory to be tested for “atypical,” or abnormal, cells. These cells are benign, but are believed by many scientists to be a precursor to cancer.

Doctors say the procedure is somewhat uncomfortable but not painful. However, aspirate can be extracted in only about 40% to 50% of women. It’s particularly hard to get adequate fluid in women over 55 — so the test is less likely to be useful in that group.

The company estimates that atypical cells will be found in about 1% of the total number of women who undergo testing. NeoMatrix, citing published literature from independent sources, says that the presence of such cells in nipple fluid increases the risk of breast cancer as much as fivefold. If a woman also has a family history of breast cancer, NeoMatrix says, the presence of atypical cells gives her as much as 20 times the average risk.

However, Mayo Clinic scientist Lynn C. Hartmann, a well-known researcher in the field, says those estimates of increased risk are too high — particularly in women with family history.Her work, including a study of 9,087 women published last year in the New England Journal of Medicine, has found that family history doesn’t add additional risk of cancer in women who have atypical cells.

The potential of nipple aspirate in assessing breast-cancer risk has long been recognized, but the test isn’t widely performed in part because of the difficulty in extracting the fluid. Some women at high risk for the disease have chosen to get a minor surgery called ductal lavage, in which a catheter is inserted into the milk ducts to collect a cell sample.

NeoMatrix’s test is noninvasive and takes only about five minutes, compared with 40 minutes or more for ductal lavage. If you test positive, NeoMatrix suggests you be seen at a center that specializes in breast cancer. Your options would include getting more frequent mammograms than normal, and possibly adding breast MRI or ultrasound, which can find tumors missed by standard mammograms. You could also consider taking preventive medications such as the anticancer drug tamoxifen.

Victor G. Vogel, a professor of medicine at the University of Pittsburgh , says the new test is a good idea for women at increased risk for breast cancer, including those whose mother or sister had the disease and women who have never had children, or had their first child after the age  of 30.

In women without other significant risk factors, Dr. Vogel says, the test may not be needed since a positive result is less likely to spur preventive action.

You may also want to visit www.yourdiseaserisk.com that was created by the Harvard Center for Cancer Prevention, stands out as one of the best health-oriented sites on the Web. Most Internet sites give users general health information, but the Harvard site has found a way to provide customized information to help patients better understand their personal health and risk for disease.

More important, it also spits out a tailored action plan on ways to lower risk for health problems.  It does all this using colorful graphics and charts that allow users to grasp how their health  stacks up against the rest of the population and how small changes in lifestyle can lower their health risks.

Another site, www.cancer.gov/bcrisktool from the National Cancer Institute, allows women to calculate their risk for breast cancer. The downside of the NCI calculator is that it uses only a few basic questions and doesn’t include the variety of factors that influence breast-cancer risk.

Update on Dec 18, 2006 — Earlier Treatment may help Prostate Cancer:

Older men with early stage, localized prostate cancer live longer if the disease is treated with radiation or surgery instead of simply waiting and watching as is often recommended, a study said.

Researchers at the University of Pennsylvania in Philadelphia said they found that patients whose cancer was treated had a 31% lower risk of death during the 12 years they were tracked than those who did nothing.

Even though the disease is considered a slow-developing one, the study “suggests a reduced risk of mortality associated with active treatment for low and intermediate risk prostate cancer in the elderly … population examined,” concluded the report published in the latest issue of the Journal of the American Medical Association.

The report was based on the medical records of more than 44,000 men 65 to 80 who were diagnosed with the disease in 1991 to 1999 and who had survived more than a year past diagnosis. The study ended at the end of 2002. In an editorial in the same issue commenting on the study, Mark Litwin and David Miller, two physicians at the University of California, Los Angeles, noted that the  findings are preliminary.

Update on Dec 19, 2006 — Abortion Drug RU-486 blocks breast cancer in Mice:

Scientists used the abortion drug RU-486 to keep tumors at bay in mice bred with a gene that makes them susceptible to breast cancer.

While no one is suggesting women use the abortion pill that way, the provocative experiment helped illustrate how the notorious breast cancer gene BRCA1 does its dirty work, by spurring a
hormone called progesterone that RU-486 happens to block.

If researchers could create a safer hormone blocker, it might offer a long-awaited alternative for women with the bad gene. They have few good options today to prevent breast cancer.

“All of us have to be cautious,” said cell biologist Eva Lee of the University of California , Irvine , who led the research published in the journal Science. “But I do think if there is a better
anti-progesterone available, hopefully there will be other options in the future for these women.”

Cancer specialists not involved with the experiment praised the work, even as they cautioned women not to get their hopes up yet.

“This is an avenue worth pursuing on a research level,” said Dr. Claudine Isaacs, an oncologist at Georgetown University Hospital who works closely with carriers of BRCA1 and a related
gene. “This is work in a mouse,” she said. “It’s clearly too early to start recommending use of this agent.”

Dr. Len Lichtenfeld, the American Cancer Society’s deputy medical chief, said researchers and patients will “take interest in this topic and explore it further.” He called the paper “elegant
research,” but stressed “it would not be appropriate in any way, shape or form that women start taking RU-486 for this purpose.”

Long-term use of RU-486 could suppress the immune system and cause other side effects.

Some 212,000 women in the U.S. will be diagnosed with breast cancer this year. Only 5% to 10% will have a hereditary form. Women who inherit mutations in the BRCA1 gene are at far greater
risk of cancer than the average woman. By age 70, more than half of those gene carriers develop either breast or ovarian cancer.

Their options today include: frequent cancer screening, in hopes of catching it early; removing both breasts while they are still healthy; taking the anticancer drug tamoxifen,
which helps some women; or removing the ovaries before age 50, cutting the risk of both cancers.

These anxiety-provoking options are propelling the push to determine exactly how BRCA1 triggers tumors, so doctors and women have better options.

Particularly puzzling, BRCA1 mutations occur in every cell of the body, raising questions about why the defect would trigger cancer just in reproductive organs.

In their research, Ms. Lee and colleagues created mice whose mammary glands only harbor the BRCA1 mutation.

The scientists found that the bad gene caused breast tissue to have too-high levels of progesterone receptors. That means the hormone sticks around longer than it should, in turn
sparking excess cell growth. In fact, the mice’s breast tissue looked like it should have during pregnancy, when temporarily high progesterone levels cause breast growth as the gland prepares
to make milk.

The final evidence came from RU-486, also called mifepristone. It causes human abortions by suppressing progesterone, a hormone crucial to sustaining pregnancy.

Instead of a human pill, Ms. Lee implanted some of the cancer-prone mice with an RU-486 pellet designed to slowly emit the drug into their bodies over two months.
By eight months of age, each of the untreated gene-defective mice had developed tumors. But none of the mice given RU-486 had developed tumors by 12 months, when the study stopped.

Ms. Lee cautioned that RU-486 isn’t a good candidate for such long-term use in people. She said more targeted progesterone blockers already are being developed.

Update on Dec 19, 2006:

Two patients taking a drug commonly used to treat cancer and rheumatoid arthritis died from a rare brain infection, the Food and Drug Administration of U.S. and the drug’smakers warned yesterday, raising questions for a promising drug.

The patients who died were receiving the drug, Rituxan, as a treatment for lupus. Rituxan, sold by Genentech Inc. and Biogen Idec Inc., isn’t approved for lupus, though doctors are
allowed to prescribe medications as they see fit. The patients contracted a viral brain infection known as progressive multifocal leukoencephalopathy, or PML.

In a preliminary public safety alert to doctors, the FDA warned that PML may be a risk for patients taking Rituxan for any reason, and they should carefully
watch patients taking the drug. In a letter to health-care professionals, Genentech said that doctors prescribing Rituxan should be on alert, particularly in patients
with lupus or certain cancers.

Update on May 29, 2007: Test for metastatic cancers:

Cancer patients often don’t realize the disease has spread until a secondary tumor grows big enough to show up on a x-ray or CT scan. Battelle Medical Device Solutions now has a
patented test that could detect a recurrence much sooner using only a routine blood sample. Battelle says its approach, developed by Thomas Haubert of its Columbus (Ohio) research lab and Dr.
Stephen Wardlaw of Yale University School of Medicine, can find a single cancerous cell in as little as 10-cc’s of blood. The system doses the sample with a fluorescent tag that sticks
to abnormal cells, which are then separated out in a centrifuge for identification.

Update on Sep 23, 2007: Promising test for Lung cancers:

A simple blood test that identifies early lung cancer before it has had a chance to spread could save lives by alerting doctors to the need for treatment, researchers say. The blood test looks for a telltale protein that is linked to tumour growth. In preliminary tests the process correctly identified 99% of patients with lung cancer at various stages of development.

Mark Semenuk, a researcher at Panacea Pharmaceuticals in Gaithersburg, Maryland, US, says a simple blood test could provide a much simpler and more effective way to screen people at high risk of developing lung cancer, such as smokers.

Semenuk and colleagues developed the test, which measures levels of a protein called human aspartyl beta-hydroxylase (HAAH) in the blood. If a person has more than 3 nanograms of HAAH per millilitre of blood, that is considered to be abnormal. This would give the clues to the doctors about the cancer.

Read more about this in New Scientist.

Update on Dec 18, 2008: Prevention of cancer using proteins

Ovarian-cancer patients who have low levels of two proteins die much sooner than women with high levels of the proteins, a finding that researchers say is a major development in the search for new treatments for the often deadly and hard-to-detect disease.

The proteins identified by researchers at the M.D. Anderson Cancer Center in Houston play a key role in two types of RNA interference, which is the mechanism by which genes are turned on or off. By targeting that process, researchers hope they will be able to silence the cancer-causing genes. In addition, measuring protein levels may eventually allow doctors to better tailor treatment plans.

In a study published in this week’s New England Journal of Medicine, the Anderson researchers said women with high levels of proteins known as Dicer and Drosha survived four times as long — or eight years — as women who had low levels of the proteins. The researchers said it is likely that low levels of the proteins allow some genes to continue functioning when they should be silenced.