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Cancer Newsletter
February 4, 2008


In This Issue
• Protein Linked With Poor Prognosis in Early-Stage Breast Cancer
• High-Dose Chemo Helps Beat Rare Brain Cancer
• Sex Hormones Don't Seem to Affect Prostate Cancer Risk
• MicroRNAs May Predict Colon Cancer Prognosis
 

Protein Linked With Poor Prognosis in Early-Stage Breast Cancer


WEDNESDAY, Jan. 30 (HealthDay News) -- High levels of a protein called Ki-67 are associated with poor prognosis in women with early-stage breast cancer, but this protein may not be useful in identifying patients who would benefit from additional chemotherapy, an Italian study suggests.

Some studies have suggested that breast tumors with a high percentage of tumors cells expressing Ki-67 are more responsive to chemotherapy. This study looked at whether Ki-67 levels predicted responsiveness to chemotherapy in women who'd had surgery for breast cancer.

Researchers at the University of Milan in Italy assessed Ki-67 expression in tumor samples from women in two randomized clinical trials comparing the use of endocrine therapy alone to endocrine therapy after chemotherapy.

They found that Ki-67 expression didn't predict which women would benefit from chemotherapy prior to endocrine therapy, but they did find that having a high percentage of tumor cells expressing Ki-67 was associated with poorer disease-free survival.

"In this study, Ki-67 [expression] was a prognostic factor, not a predictive factor," the study authors wrote.

The findings were published in the Jan. 29 issue of the Journal of the National Cancer Institute.

These results support the position of the American Society of Clinical Oncology Tumor Markers Expert Panel that Ki-67 shouldn't be used to make decisions about chemotherapy, Matthew Ellis, of Washington University in St. Louis, wrote in an accompanying editorial.

"Biomarker studies with negative results can be just as important to publish as those with positive results, because clinging to a long-favored but incorrect hypothesis in the face of negative evidence impedes scientific and clinical progress," Ellis wrote.

More information

Breastcancer.org has more about breast cancer treatment  External Links Disclaimer Logo.


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High-Dose Chemo Helps Beat Rare Brain Cancer


WEDNESDAY, Jan. 30 (HealthDay News) -- Most people suffering from a rare brain cancer appear to benefit from high doses of the chemotherapy drug methotrexate, a small study finds.

Primary central nervous system lymphoma (PCNSL) is a type of non-Hodgkin lymphoma that affects the brain. Although it is typically very difficult to treat, it can be cured or sent into long remissions. Current treatment is often a combination of radiation and chemotherapy. Newer approaches involve giving chemotherapy first, and waiting on radiation until the results of chemotherapy are seen.

However, "A subset of these patients with a rare form of non-Hodgkin lymphoma appeared to be cured by chemotherapy alone," explained lead researcher Dr. Tracy Batchelor, from the Massachusetts General Hospital Cancer Center in Boston.

Batchelor, who is executive director of the Stephen E. & Catherine Pappas Center for Neuro-Oncology at the hospital, noted there are about 1,500 new cases of PCNSL diagnosed in the United States each year.

In the study, Batchelor's group treated 25 adults with newly diagnosed PCNSL with a high dose of methotrexate every two weeks for four months, or until there were no signs of the brain tumor. The patients were followed for a minimum of 6.5 years.

The report appears in the Jan. 29 issue of Neurology.

Batchelor's team found that 52 percent of the patients had a complete remission of their cancer and 40 percent had not had a relapse after seven years. Average survival of all patients who received methotrexate was 4.5 years, compared with one year among patients who had radiation therapy.

It's clear that methotrexate is the best drug to treat this tumor, Batchelor said. "The drug attacks cells that are dividing. Other drugs don't have as high a response rate," he explained.

Batchelor noted that it is unusual for a single drug to achieve remission in cancer.

More studies are needed to find the most effective dose of methotrexate and to find a combination therapy that will produce even better results, Batchelor said. "The question is whether adding other drugs will make patients do better," he said.

"We are looking for drugs that act against lymphoma and actually get into the nervous system," Batchelor said. "We have a new trial where we will be adding three additional drugs to methotrexate. We hope we are going to see even more patients achieve long-term remission."

One expert believes that, based on these findings, methotrexate could save many patients from having to undergo harmful brain radiation.

"Methotrexate is to date the most effective reported drug in primary central nervous system lymphoma," said Dr. Paul Graham Fisher, an associate professor of neurology and the Beirne Family Director of Neuro-Oncology at Packard Hospital at Stanford University.

This is encouraging because in some rare instances patients may not need radiation treatment, Fisher said. "As a cautionary note, the numbers of patients are small, and we need to see greater extension of this work, and also with monitoring patients for leukoencephalopathy (destruction of fibers covering nerve cells), apparently seen more widely when used in children with leukemia," he said.

Methotrexate is commonly used in chemotherapy and is also used in treating autoimmune diseases such as Crohn's disease, psoriasis and arthritis.

More information

For more on primary central nervous system lymphoma, visit the U.S. National Cancer Institute.


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Sex Hormones Don't Seem to Affect Prostate Cancer Risk


TUESDAY, Jan. 29 (HealthDay News) -- A man's risk of prostate cancer is not related to the amount of sex hormones circulating in his bloodstream, a new British analysis suggests.

The conclusion was based on a review of 18 studies -- representing 95 percent of all available research -- that looked into potential links between the disease and blood hormone levels, the study authors said.

"There has been a long interest in whether or not natural variations in hormone levels in a man's blood are related to future disease risk," said study author Andrew Roddam, of the Cancer Research UK Epidemiology Unit at the University of Oxford. "What we have shown in this collaboration is that these natural fluctuations in levels of androgens [and estrogens] do not appear to be related to subsequent risk [for] the disease."

The findings were published online in the Jan. 29 issue of the Journal of the National Cancer Institute.

Prostate cancer is the most common type of cancer in American men, other than skin cancer. An estimated 220,000 new cases of prostate cancer were diagnosed in the United States in 2007, and about 27,000 men died from the disease, according to the American Cancer Society.

Although there's no single known cause of prostate cancer, risk is higher for those over the age of 50, black men, and those with a family history of the disease.

High levels of male sex hormones, known as androgens, have long been believed to be a risk factor for prostate cancer. To explore a possible hormone-cancer risk connection, Roddam and his colleagues analyzed data from studies that involved more than 10,000 men with and without prostate cancer. The research had been conducted between 1961 and 2001, and most study participants with prostate cancer had been diagnosed after the age of 60.

After compensating for other factors -- such as age, body-mass index, marital and educational status, smoking history and alcohol consumption -- the study authors found no statistical correlation between pre-diagnosis sex hormone concentrations in the bloodstream and the risk for developing prostate cancer.

Similarly, no hormone level combination -- such as a very high concentration of one sex hormone and a very low concentration of another -- was associated with prostate cancer risk.

In an accompanying editorial, co-author Dr. Paul A. Godley, an associate professor of medicine at the University of North Carolina School of Medicine, said the "impressive" findings could push prostate cancer research in a new direction.

"Researchers should redirect their attention toward investigations of potentially modifiable nutritional, lifestyle or environmental risk factors," he suggested, rather than target unchangeable factors -- such as blood hormone levels -- that do not appear to affect risk.

But, Dr. Peter T. Scardino, chairman of the department of surgery at Memorial Sloan-Kettering Cancer Center in New York City, cautioned that it would be wrong to conclude that male hormones have nothing to do with prostate cancer.

"This study asks if the amount of male or female hormones in your bloodstream can predict whether you will get prostate cancer, and the answer is no," he said. "But the prostate is like a sponge for hormones that sucks them out of circulation and converts them to even more powerful forms that can go to work in the prostate. So blood hormone levels may not have any connection with the amount of hormone in the prostate gland itself.

"The point is," he added, "I would not want people to think that altering the male hormone environment in the prostate has no effect. It certainly will. So if you take drugs like finestaride to shrink your prostate to urinate better, or Propecia to prevent balding, these drugs are working directly on hormone levels in the prostate, not the bloodstream. And these drugs work very well."

More information

For additional information on prostate cancer risk, visit the American Cancer Society  External Links Disclaimer Logo.


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MicroRNAs May Predict Colon Cancer Prognosis


TUESDAY, Jan. 29 (HealthDay News) -- Knowing whether or not a particular cancer will be aggressive allows doctors to more effectively treat their patients, and a newly found class of molecules called microRNAs may help doctors do just that.

Recent research has honed in on a particular microRNA, designated miR-21, that may predict outcomes in people with colon cancer. Tumor cells with high levels of miR-21 were associated with more than twice the risk of poor survival, according to a study in the Jan. 30 issue of the Journal of the American Medical Association.

"Progress is being made that is going to eventually lead to better diagnosis and predicting prognosis," said one of the study's authors, Dr. Curtis Harris, chief of the lab of human carcinogenesis at the U.S. National Cancer Institute in Bethesda, Md. "This is a new area of research that may develop exciting new therapies, but we're very early in the discovery phase. It's only been about five years since we've known about microRNA."

Colon cancer is the third most common type of cancer in the United States, and the second-leading cause of cancer death, according to background information in the study. Surgical removal of colon cancer is currently the only curative form of therapy, according to the study.

MicroRNA molecules are an attractive research target because they help control many cell functions -- from division to proliferation to apotosis (programmed cell death). They have also been implicated in the development of cancer. MicroRNA expression has been found to be altered in other malignancies, such as leukemia, lung cancer, and pancreatic cancer, the researchers said.

The researchers theorized that microRNA production was probably altered in colon cancer as well, and if they could isolate which microRNA was associated with poorer prognosis, this could eventually help clinicians decide who needs more aggressive treatment and who would likely do well with a less aggressive regimen.

For the study, the researchers examined colon cancer tumors and non-tumorous tissue from 84 people in the United States, looking specifically at microRNA expression. To validate the U.S. findings, Hong Kong researchers also examined tumors and non-tumorous tissues from 113 Chinese adults.

The scientists found that 37 microRNAs were expressed in different levels in the tumor tissue. However, only one -- miR-21 -- was statistically significantly associated with poorer outcome. MiR-21 was also found in precancerous tissues.

Tumors that expressed high levels of miR-21 were associated with a 2.5 times increased risk of poor survival in the U.S. group, and 2.4 times increase in the risk of poor survival outcomes for the Hong Kong group.

"These are two different clinical cohorts [groups of patients] that found a single microRNA could have prognostic significance," said William Phelps, scientific program director in the research department of the American Cancer Society.

"The association was not only associated with a less favorable outcome, but was also associated with a poorer response to therapy, independent of the stage of the tumor. This seems to suggest that miR-21 is a very early marker that predicts a poorer prognosis," Phelps said.

However, both Harris and Phelps said this study's findings need to be duplicated in a larger group and in different populations before they could be applied in practice to help predict how a particular cancer might behave.

More information

To learn more about colon cancer, visit the U.S. National Library of Medicine.


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