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June 6, 2002 Not knowing which tumors will respond to chemotherapy is a major concern for breast cancer patients and their doctors, but a new test may take some of the guesswork out of these treatment decisions. Researchers now say they’ve developed a test that can predict with 100% accuracy which women will respond to chemotherapy.

According to researchers, resistance to chemotherapy is the biggest cause of treatment failure in breast cancer patients. Up to half of untreated cancers are resistant to chemotherapy, and resistance is acquired later in treatment by up to 75% of women.

The laboratory tests currently used to help determine which patients will respond well to chemotherapy are not very reliable.

But the study, which appears in the June issue of The Journal of Nuclear Medicine, shows that researchers were able to accurately make this determination using a technique known as scintigraphic imaging.

The method involves injecting the patient with a radioactive substance, which accumulates in the targeted organ in this study, the breast. The patient is then scanned with a special gamma camera that picks up signals from the substance and produces an image that shows how the organ is functioning.

Using this information, study authors Rosa Sciuto, MD, and colleagues at the Regina Elena Cancer Institute in Rome, were able to predict 100% of the time which of 30 untreated women with breast cancer would respond to chemotherapy and 83% of the time which of them would not.

The test works by measuring how quickly the radioactive substance is washed out of the breast. If the substance washes out quickly, this is a sign that chemotherapy alone will not work. If the substance stays in the breast, however, then it looks like the chemotherapy will work 100% of the time, according to the results of this study.

If the test shows that chemotherapy alone is unlikely to work, that doesn’t mean all hope is lost. The researchers say knowing which tumors are not likely to respond to chemotherapy alerts them to use drugs to increase the body’s response to chemotherapy.

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Scientists have discovered six more abnormal genes that can increase the chance of developing breast cancer. The new findings may one day lead to new drugs that are more effective than the treatments currently available.

And the finding, appearing in the June 13 online edition of the journal Science, may lead to more tests that are able to screen for inherited breast cancer.

“Just as women today can be tested for BRCA1 and BRCA2 [gene] mutations to determine if they have an inherited predisposition for breast cancer, testing for mutations in these other six genes may soon become a routine part of gauging inherited breast cancer risk,” says study author Alan D’Andrea, MD, of the Dana-Farber Cancer Institute in Boston, in a news release. “Women and their doctors can then use the information in deciding how to keep that risk at a minimum.”

BRCA1 and BRCA2 are the names given to the first two genes discovered to be linked to breast cancer.

Prior research has found that between 50% and 85% of women with abnormal BRCA1 or BRCA2 genes will develop breast cancer by age 70, compared with the roughly 11% lifetime risk that the average American woman faces. But these genetic markers only explain a small number (about 5% to 10%) of all breast cancer cases.

The study shows that a defect or mutation in any of the half-dozen genes involved in causing a rare childhood blood disease known as Fanconi anemia can increase a person’s chance of developing breast cancer.

Fanconi anemia is an extremely rare condition in which the bone marrow fails to produce enough blood cells to meet the body’s needs.

Children born with the condition often require a bone marrow transplant to survive into young adulthood, and they are at risk for developing a variety of cancers including leukemia and tumors of the brain, breast, head and neck, colon, or other parts the body.

Researchers say the six abnormal genes that cause Fanconi anemia can trigger a chain reaction that hampers the normal activity of the BRCA1 and BRCA2 genes, which are responsible for repairing damaged DNA. If either of these genes isn’t working properly or becomes damaged, DNA damage accumulates in cells and increases the chance that cells will become cancerous.

Researchers say by identifying the link between genetic mutations for Fanconi anemia and breast cancer, scientists may be able to develop new tests to determine who is at risk for inherited breast cancer and possibly create new treatments to correct the flawed genes.

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A simple new test may help determine which prostate cancer patients have a tumor that’s more likely to spread to other organs and help doctors give the best treatment. And the test may eventually be able to predict the aggressiveness of other types of cancer.

Currently, the degree to which prostate tumors have progressed is determined by looking at the shape and appearance of the cancer cells under a microscope. The tumor is then given a score between 2 and 10 (with 10 being the most advanced cancer) called a Gleason score.

Men with a higher score have tumors at a more advanced stage of the disease, but the grading system does not take into account how fast the tumor is growing or spreading.

“That means that within any score, there are biologically aggressive and less aggressive forms of cancer,” says study author Akhouri Sinha, PhD, professor of genetics and cell biology at the University of Minnesota Cancer Center, in a news release. “This makes it more difficult to predict outcomes for individual patients.”

The new test, which Sinha developed along with the creator of the Gleason score, Donald Gleason, MD, PhD, takes into account two biological factors that help determine which tumors are more likely to spread.

To grow and break through surrounding healthy tissues, tumors produce an enzyme known as cathepsin B (CB), which destroys the proteins in the tissue that hold the cells in place. But at the same time, the cells also produce substances called stefins that act as CB’s natural enemies and inhibit the destructive enzyme.

After analyzing tumor samples from 97 men with prostate cancer and eight men with noncancerous enlargement of the prostate, researchers found that the ratio of how much CB the tumor had in relationship to how much of the stefin it contained predicted whether the cancer had spread to one or more of the pelvic lymph nodes.

If the tumor had more CB than stefin, it was more likely to be aggressive and spread. But if the tumor had more stefin, it was less aggressive.

“The ratio of CB to stefin A reveals differences in tumors that are not visible under the microscope,” says Sinha. “If this test were done on tumors of newly diagnosed patients, we would have an indication of which cancers were most aggressive, and we could give those patients aggressive treatment.”

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Women with early breast cancer may soon have an alternative to the standard treatment with tamoxifen. Data from the largest study to date evaluating a highly anticipated new hormone therapy show the drug Arimidex to be slightly better than tamoxifen for preventing cancer recurrence and cancer deaths.

The results suggest that Arimidex and two other drugs in the class known as aromatase inhibitors could one day replace tamoxifen as the hormonal treatment of choice for most breast cancers. But experts say it is too early to make the change.

“Our feeling is that there would be greater risk associated with a widespread switch from tamoxifen to the aromatase inhibitors than there would be benefits at this point, but this is something we will have to monitor as more data come in,” says Eric Winer, MD. Winer is director of the Breast Oncology Center at Boston’s Dana-Farber Cancer Institute, and he led a panel of experts who weighed in last month on the Arimidex vs. tamoxifen debate.

Currently, postmenopausal women with small breast cancers that haven’t spread outside the breast are offered tamoxifen in addition to surgery to remove the tumor. Tamoxifen is a form of hormone therapy that blocks the ability of the hormone estrogen to promote cancer growth. The drug does have risks, however, namely hot flashes, vaginal bleeding, and increased risk of cancer of the uterus, stroke, bone-thinning osteoporosis, and blood clotting.

Arimidex and the other aromatase inhibitors block estrogen in a different way. Early studies show it may be safer than tamoxifen. In fact, its already replacing tamoxifen as the treatment of choice for many women with advanced breast cancers that have spread outside the breast.

In this ongoing international trial, approximately 9,000 postmenopausal women with early, localized breast cancer are being treated with tamoxifen alone, Arimidex alone, or a combination of the two drugs.

Women taking Arimidex alone had an improved disease-free survival rate at three years of approximately 90% (women on tamoxifen had a disease-free survival rate of 87%). No benefit over tamoxifen alone was seen in women taking the combination regimen.

Patients taking Arimidex alone had fewer of the treatment-related complications associated with tamoxifen use. But they have also reported more osteoporosis and related bone fractures than tamoxifen-treated patients. The interim findings from the first three years of the five-year trial were published in the latest issue of the journal The Lancet.

Breast cancer patients are at increased risk of having a tumor occur in the nontreated breast. Lead researcher Michael Baum, MD, tells WebMD that the Arimidex group has experienced significantly fewer of these so-called contralateral breast cancers than the women treated with tamoxifen.

“This is one of our most interesting findings,” he says. “We know that tamoxifen reduces the risk of breast cancer [in the other breast] by 50%. Patients on Arimidex had a 60% reduction compared with tamoxifen.”

Your snacking habit is safe for now. A group of international health experts says there is not enough evidence to prove that a substance found in many carbohydrate-rich foods such as potato chips, french fries, cookies, and cereals can cause cancer in humans.

But the group says recent findings about high levels of acrylamide a substance known to cause cancer in animals in common snack foods is a “major concern,” and more research is needed.

“After reviewing all the available data, we have concluded that the new findings constitute a serious problem,” said Dieter Arnold, director of Germany’s Federal Institute for Health Protection of Consumers, in a statement. “But our current limited knowledge does not allow us to answer all the questions which have been asked by consumers, regulators and other interested parties.”

Arnold led the three-day meeting on the issue of acrylamide in food, which was hosted by the World Health Organization (WHO) and the United Nations Food and Agriculture Organization in Geneva, Switzerland.

Two months ago, a group of Swedish researchers announced that laboratory tests showed that baking or frying starchy foods such as potatoes, breads, and cereals at high temperatures created levels of acrylamide in these foods that are higher than those allowed by the WHO.

For example, they found a bag of potato chips may contain up to 500 times more of the substance than allowed in drinking water by the WHO. Those safety recommendations permit one microgram (one-millionth of a gram) of acrylamide per liter of drinking water.

But the expert panel says that although acrylamide is known to cause cancer in laboratory animals, no studies of the relationship between acrylamide and cancer in humans have been done. And the theoretical models used to predict whether humans may also develop cancer from average intake levels of the substance are not reliable enough to draw firm conclusions about risk.

The group says research has shown acrylamide’s potency is similar to that found in other known cancer-causing substances such as certain types of hydrocarbons formed in meats when grilled or fried.

But although the average daily intake of acrylamide for most people is likely to be higher (around 70 micrograms a day from all food sources), experts say the range would still be lower than that shown to cause nerve damage in laboratory animals.

“The claim that acrylamide, found in common foods such as potatoes and bread, after cooking, poses a human cancer risk is based exclusively on high dose studies in laboratory animals,” said Elizabeth Whelan, MD, president of the American Council on Science and Health, in a statement released after the Swedish study was announced in April. “There is no evidence whatever that humans who eat the observed levels of acrylamide are exposed to any risk of any cancer.”

Parkinson’s disease and depression often go together, and
depression is often untreated in Parkinson’s patients, a new study shows.

Doctors and patients may mistake depression symptoms as part of Parkinson’s
disease, note the researchers.

They included Barnard Ravina, MD, MSCE, of the neurology department at New
York’s University of Rochester, and Richard Camicioli, MD, of the neurology
department at Canada’s University of Alberta.

“It is crucial for health care professionals to make an effort to
detect, diagnose, and properly treat depression in Parkinson patients,”
says Camicioli in a University of Alberta news release.

Parkinson’s and Depression Study

The researchers followed 413 newly diagnosed Parkinson’s disease patients
for nearly 15 months.

When the study began, the patients hadn’t started taking Parkinson’s disease
drugs, since they were still in the early stages of Parkinson’s disease.

Parkinson’s disease is a brain disease that develops gradually. It affects
certain brain cells that make a chemical called dopamine, which the brain uses
to coordinate the body’s movements.

As dopamine-making brain cells die, Parkinson’s symptoms develop, including
tremor, difficulty walking, and problems with balance.

In the new study, Parkinson’s patients completed surveys about their
depression symptoms every six months.

Overall, more than a quarter of the patients nearly 28% were depressed
during the study. Among the depressed patients, 40% of those patients didn’t
get depression treatment (antidepressants or referral for further psychiatric
evaluation).

Depressed Parkinson’s Patients

When the study started, about a quarter of the patients reported a history
of depression and almost 14% of all patients were currently depressed.

During the study, 57 patients became depressed.

Depressed patients were more likely to report having problems with daily
tasks and to start taking Parkinson’s disease drugs sooner than patients who
weren’t depressed.

Depressed patients also reported lower quality of life than patients who
weren’t depressed. But depression didn’t appear to aggravate movement problems
over time.

Typical depression cases were mild but still hampered the patients’ lives.
Severely depressed patients were more likely to get depression treatment.

The results “suggest that depression, particularly mild depression, is
common early in [Parkinson's] disease and is associated with increased
disability,” write the researchers.

They write that some depressed patients remained depressed despite
depression treatment and may have needed more intensive psychiatric care.

Some doctors may have attributed depression symptoms to Parkinson’s disease,
the researchers also suggest.

They call for further studies on recognizing and treating depression in
Parkinson’s disease patients.

There’s no doubt that new drugs called SERMs can prevent breast cancer. The problem is that nobody’s quite sure how to use them yet.

The drugs are tamoxifen (sold as Nolvadex) and Evista. They are drugs that act like estrogen on some cells in the body and in other cells block the action of estrogen. Clinical trials show that both drugs can prevent breast cancers that need estrogen to grow. So far, the FDA has approved only tamoxifen for breast cancer prevention. Evista is FDA approved for treating bone loss after menopause.

Eli Lilly and Company, the maker of Evista, is a WebMD sponsor.

A team of distinguished breast cancer experts took a look at all clinical trials of the two drugs. Their report upon which the U.S. Preventive Services Task Force will base its official recommendations appears in the July 2 issue of Annals of Internal Medicine. Lead author Linda Kinsinger, MD, MPH, is co-director of the prevention program at the University of North Carolina School of Medicine in Chapel Hill.

“The bottom line is that these medicines offer some promising opportunities,” Kinsinger tells WebMD. “The target group is still small, no more than 10% of women in general. The drugs are not for everyone. But for one group women generally in their 40s to 50s with increased risk of breast cancer but who don’t have increased risk for the drugs’ side effects these women should talk with their doctors about them.”

European studies failed to find a prevention benefit for tamoxifen. While Kinsinger and her fellow experts can’t entirely explain this, they suggest that too few women in these studies took the drug long enough for maximum effect. Also, these studies may have had too few women with estrogen-sensitive breast cancer.

A large U.S. study got much different results. It looked at more than 13,000 women age 35 or older with a relatively high risk of breast cancer. It showed that tamoxifen cut breast cancer risk in half. To prevent one case of breast cancer, the study showed, 47 women would have to take tamoxifen for five years.

There’s been only one large study of Evista’s ability to prevent breast cancer. It looked at a different group of women: 7,705 postmenopausal women with osteoporosis. In this group, Evista cut breast cancer risk by 76%. To prevent one case of breast cancer, 126 women would have to take Evista for 40 months.

Both tamoxifen and Evista have side effects. Both increase the risk of blood clots in the legs and lungs, Kinsinger says. But she’s quick to point out that this risk is no greater than the risk of taking estrogen-containing hormone-replacement therapy. Unlike Evista, tamoxifen increases a woman’s risk of uterine cancer. Each drug also has other annoying but less drastic side effects.

where the cancer had not spread outside the prostate, but the cancer cells were aggressive. The men received radiation therapy alone or radiation plus male hormone suppression treatment, at medical centers throughout Europe.

Hormone suppression was achieved with the drug Zoladex, which decreases the amount of testosterone in the body. Zoladex was given while the men received radiation and for three years afterward.

More than five years after treatment began, 78% of the men who received male hormone suppression were still alive compared with 62% of those given radiation alone. In addition, 74% of the men who got the combination treatment had no sign of prostate cancer recurrence, compared with 40% of the men treated solely with radiation.

The study appears in the July 13 issue of the medical journal The Lancet.

Study leader Michel Bolla, MD, notes that male hormone suppression appears to improve outcome in men who also receive radiation by promoting tumor cell death. He adds that improvements in radiation treatment since this study was conducted should mean even better outcomes with the combination approach in the future.

Fogel tells WebMD it is not yet clear how long men need to be treated with hormone suppression. In this study, the men were treated for three years, but many doctors give the treatment for a year or less. Hot flashes, muscle loss, and bone loss are common side effects of treatment. Fogel is a spokesperson for the American Cancer Society and is with the Coastal Radiation Oncology Group in Santa Maria, Calif.

“There are still many unanswered questions here,” he says. “There is no consensus on which patients should receive this therapy or how long it should be given. But this long-term follow up shows that it does improve both overall and disease-free survival.”

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The number of people who die of cancer each year may actually be much higher than thought. A new report claims that if all deaths from cancer were properly categorized, overall cancer death rates would rise by about 1%, or about 5,500 deaths.

Researchers and government agencies often rely on information about cancer death rates to measure progress in the fight against the disease. But researchers say deaths from cancer treatments are often not listed as “cancer deaths.”

Currently, researchers consider deaths that happen within 30 days of surgery to be caused by the surgery rather than the cancer that prompted it.

Researchers say that has created a system in which more than two out of five deaths that occur within a month of cancer surgery are considered treatment related and not attributed to cancer. The study is published in the July 17 issue of the Journal of the National Cancer Institute.

When the researchers looked at more than 4,000 deaths in people with cancer, they found that 41% were attributed to a cause other than cancer. The proportion of deaths not attributed to cancer ranged from 13% among cervical cancers to 81% among laryngeal cancers.

Study researchers H. Gilbert Welch, MD, and William C. Black, MD, of Dartmouth Medical School say that this trend of misclassifying deaths is particularly common among cancers that are now being detected and treated much earlier, such as breast and prostate cancers. The study found 59% of breast cancer deaths and 75% of prostate cancer deaths that occurred within one month of cancer-related surgery were not attributed to the underlying cancer.

The researchers say that the current system of classifying cancer deaths does not allow us to best use the information to make judgments about progress against cancer. A broader system of classification should be adopted that includes all deaths within one month of surgery, radiation therapy, or chemotherapy as attributable to the cancer that initiated the treatment.

But in an editorial that accompanies the study, Colin B. Begg, PhD, and Deborah Schrag, MD, of the Memorial Sloan-Kettering Cancer Center in New York, say changing the way cancer-related deaths are classified may create more inaccuracies.

The editorialists argue that deaths occur suddenly and unpredictably, especially among older patients, and many deaths have multiple causes. Therefore, they write, attributing the cause of death to one disease does not recognize the complexity of the issue.

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Taking folic acid supplements may reduce the risk of colon cancer in people who are most likely to get the disease. A new study shows regular supplementation of folic acid (found naturally in foods as folate) can reduce abnormal cell activity in the colon, which is an early sign of colon cancer.

The importance of a healthy diet in preventing colon cancer has been debated a lot lately due to the results of several conflicting studies. Previously, it had been thought that fruits and vegetables helped reduce colon cancer risk by virtue of their fiber content alone. But some newer studies have suggested that fiber intake has little effect on preventing colon cancer.

However, researchers say not getting enough fruits and vegetables in your diet has also been found to increase the risk of colon cancer. That means there may be other ways in which the nutrients in fruits and vegetables, such as folate, protect against the disease.

That prompted a group of Irish researchers from the Institute of Clinical Science at Royal Victoria Hospital in Belfast to measure the effects of folate supplementation on a cell proliferation process that is believed to be a precursor to colon cancer. Their findings are published in the July issue of Gut.

For the study, 11 people who had a history of recurrent precancerous growths were divided into two groups. One group was given 2 mg of folic acid per day for three months and the other a placebo.

At the start of the study, there was no difference between the two groups. But at the end, researchers found that abnormal cell activity dropped significantly in the group that received a daily dose of folic acid. But these potentially dangerous activity levels remained unchanged in the group that did not receive supplements.

When the supplements were stopped, the cellular activity began to return to pre-study levels in the folic acid group. Researchers say these findings suggest that folate seems to reduce the risk of colon cancer in susceptible people by repairing cellular damage after it has occurred.

The study authors say if more studies confirm these results, folic acid supplementation may be a valuable new way to lower the risk of colon cancer in people at high risk for the disease. But they caution that folic acid supplements may be harmful for people who have advanced cancer, are taking drugs for epilepsy, or are vitamin B-12 deficient.

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