31 replies to this topic

[kevin]

Link: http://www.eurekaler...c-ddm091503.php
Date: 09-15-03
Author: Lindsey Spindle
Source: Georgetown University Medical Center
Title:Diabetes drug may be new tool in treating breast cancer

---

Public release date: 15-Sep-2003

Contact: Lindsey Spindle
las46@georgetown.edu
202-687-7707
Georgetown University Medical Center

Diabetes drug may be new tool in treating breast cancer

Washington, D.C – Researchers at Georgetown University's Lombardi Comprehensive Cancer Center have decoded the step-by-step process by which a class of popular anti-diabetes drugs inhibits cancerous tumor growth. With the discovery of this molecular chain of events, as reported in the September 2003 issue of Molecular and Cellular Biology, the Georgetown researchers are now studying whether these anti-diabetes drugs, called glitazones, could one day be effective anti-cancer drugs.

Glitazones are taken by more than two million people with Type 2 diabetes. They are marketed under the names AvandiaTM and ActosTM, by SmithKline Beecham and Eli Lilly, respectively. Glitazones bind to a particular target on a cell, and in diabetics, they work by reducing insulin resistance at the sites of insulin action in the muscle and liver. Previous studies have also shown that glitazones also have the ability to inhibit tumor growth. However, until this study no one understood how this process worked.

"This study shows for the first time a direct link between a gene causing breast and other cancers and a gene linked to diabetes and the production of fat cells," said Richard Pestell, M.D., PhD, director of Lombardi Comprehensive Cancer Center. "The link between these cellular components may be a lynchpin in some cancers – linking some cancers and metabolism directly. Potentially, we could be on the way to finding new therapeutic leads that would improve both diseases."

Pestell and his colleagues describe a complex relationship between a cancer causing gene, Cyclin D1, and a cancer-blocking receptor called PPAR gamma, which is involved in fat cell development. They are respectively found in breast cancer tissue and normal breast tissue. When PPAR is "turned on" by glitazones, tumor growth is inhibited. Conversely, when Cyclin D1 is activated in cells, it causes cancer cells to divide uncontrollably and excessively.

The new study reports that the anti-tumor effects of the PPAR gamma receptor are actually controlled by the cancer-causing Cyclin D1. In short, too much Cyclin D1 trumps the PPAR gamma receptor, turning off its ability to inhibit tumor growth.

Based on these findings, the Georgetown researchers believe that reduction in PPAR expression coupled with the increase in Cyclin D1 may represent a key genetic alteration underlying the transition from normal breast tissue to breast cancer. These findings suggest that drugs that block the effects of Cyclin D1 may be useful in stopping the conversion of normal tissue to malignant tissue.

The discoverer of the human Cyclin D1 gene, Andrew Arnold, M.D., professor and Director of the Center for Molecular Medicine at the University of Connecticut School of Medicine, agrees with the Georgetown researchers.

"This link between Cyclin D1 and PPAR gamma biochemical pathways is fascinating and clearly worthy of further exploration, including the potential for yielding new treatment modalities for cancer," said Dr. Arnold.

The study published in Molecular and Cellular Biology was funded by the National Cancer Institute.


###
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area. For more information, go to www.georgetown.edu/gumc.

The Nina Hyde Center for Breast Cancer Research promotes and supports the diverse breast cancer research conducted at the Lombardi Cancer Center. Named in honor of the acclaimed Washington Post fashion editor who died of breast cancer in 1990 at the age of 57, the center was founded in 1990 by her longtime friends Ralph Lauren and former Washington Post owner Katharine Graham. The breast cancer researchers affiliated with the Nina Hyde Center are internationally recognized in an elite class of scientific innovators.

[chubtoad]

http://www.scienceda...31010072141.htm
Source: NIH/National Cancer Institute
Date: 2003-10-10

New Treatment Improves Long-term Outlook For Breast Cancer Survivors
October 9, 2003 -- A Canadian-led international clinical trial has found that post-menopausal survivors of early-stage breast cancer who took the drug letrozole after completing an initial five years of tamoxifen therapy had a significantly reduced risk of cancer recurrence compared to women taking a placebo. The results of the study appear in today's advance on-line edition of the New England Journal of Medicine.

The clinical trial has been halted early because of the positive results and researchers are notifying the 5,187 women worldwide who have participated in the study. Women on letrozole will continue taking the drug and those on the placebo can begin taking letrozole, if they wish.

"This very important advance in breast cancer treatment will improve the outlook for many thousands of women," said Andrew von Eschenbach, M.D., director of the National Cancer Institute which led the study in the United States. "This is one more example of the ability to interrupt the progression of a cancer using a drug that blocks a crucial metabolic pathway in the tumor cell."

Study researchers found that letrozole, when taken after five years of tamoxifen therapy, substantially increased the chance of remaining cancer free. In total, 132 women taking the placebo had their disease recur compared to 75 on letrozole. Overall, letrozole reduced the risk of recurrence by 43 percent, so that after four years of participating in the trial, 13 percent of the women on the placebo, but only seven percent, of those on letrozole had recurred. Deaths from breast cancer were also reduced. Seventeen women taking the placebo died of breast cancer compared to nine taking letrozole.

While tamoxifen is widely used to prevent breast cancer recurrence in post-menopausal women, it stops being effective after five years because, researchers believe, tumours become resistant to it.

"More than half of women who develop recurrent breast cancer do so more than five years after their original diagnosis," says Paul Goss, M.D., of Princess Margaret Hospital in Toronto. "For years, we have thought that we had reached the limit of what we could do to reduce the risk of recurrence with five years of tamoxifen. Our study ushers in a new era of hope by cutting these ongoing recurrences and deaths from breast cancer after tamoxifen by almost one half." Goss, a leading expert in novel hormone therapies for the treatment and prevention of breast cancer, conceived and chaired the international trial with letrozole.

A form of hormone therapy for the treatment of breast cancer, letrozole works by limiting the ability of an enzyme called aromatase to produce estrogen, a major growth stimulant in many breast cancers.

Mayo Clinic medical oncologist James Ingle, M.D., says, "Based on our findings, all post-menopausal women with hormone-receptor positive tumours completing about five years of tamoxifen should discuss taking letrozole with their doctors to reduce their risk of breast cancer recurrence." Ingle, from Rochester, Minn., led the research study in the United States.

With Canadian Cancer Society funding, the clinical trial was coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queen's University, in partnership with the U.S. National Cancer Institute and its Clinical Trials Cooperative Groups. Novartis, which manufactures letrozole, also known as Femara®, provided the drug for the trial.

Women participated in the study for an average of 2.4 years and for as long as five years. The study found that women taking letrozole had a reduction in the number of recurrences of cancer in their previously affected breast, a reduction in the number of new cancers in their opposite breast, and a reduction in the spread of the cancer outside their breast.

The side effects of letrozole, a pill which is taken once a day, are very similar to those experienced by women undergoing menopause. They were generally mild in study participants. Women in the study will continue to be followed to more thoroughly assess any effects of long-term use of letrozole on bone strength or other organs. Until these are known, patients should be monitored closely.

"The Canadian Cancer Society is pleased to have made a key contribution to this study," says Barbara Whylie, M.D., director of Cancer Control Policy for the Canadian Cancer Society. "We estimate that more than 20,000 Canadian women will be diagnosed with breast cancer this year and just over half of those are going to be eligible for this drug. That means these women will have a significantly improved hope for a future without cancer."

"This large trial only began in 1998 and we already have important results that will change clinical practice," says Jeffrey Abrams, M.D., coordinator of the U.S. National Cancer Institute's Cooperative Group breast cancer treatment trials. "This is a tribute to the patients and physicians who participated since their efforts will now have a positive impact on so many lives."

Participants in the clinical trial were enrolled through hospitals, cancer centers and institutes throughout Canada, the United States, England, Belgium, Ireland, Italy, Poland, Portugal and Switzerland. The European Organization for Research and Treatment of Cancer and the International Breast Cancer Study Group coordinated the European component of the trial.

[chubtoad]

http://www.scienceda...31016063250.htm
Source: University Of Pittsburgh Medical Center
Date: 2003-10-16

Use Of Statins May Prevent Breast Cancer, Say University Of Pittsburgh Researchers
PITTSBURGH, Oct. 16 – Cholesterol-lowering medications may help to prevent breast cancer in older women, according to study findings published by University of Pittsburgh researchers in the October issue of the Journal of Women's Health.

"While scientists have known for years that cholesterol inhibition serves to inhibit tumor cell growth, our analysis is one of the first to look exclusively at the relationship between lipid-lowering medications and the development of breast cancer, and our findings are dramatically positive," said study author and lead investigator Jane Cauley, Dr.P.H., professor of epidemiology at the University of Pittsburgh Graduate School of Public Health.

The Pittsburgh-led study found that older women who took statins and non-statin lipid-lowering drugs experienced a 60 to 70 percent reduction in their risk of breast cancer over approximately seven years.

Researchers reviewed data on 7,528 white women age 65 years and older who participated in the Study of Osteoporotic Fractures at sites in Pittsburgh, Baltimore, Minneapolis and Portland, and followed them for seven years.

A total of 234 (3.3%) cases of breast cancer were reported among the 6,952 participants who reported no use of lipid-lowering drugs; six cases (2.1%) among the 284 women who used statins; and four cases (1.3%) among the 292 who used nonstatin lipid-lowering drugs. The combined group of lipid-lowering drug users had a 68 percent reduction in the risk of breast cancer.

Investigators adjusted for body mass index and other risk factors for breast cancer such as the age at menarche, age at first birth, parity, physical activity and alcohol consumption. The results were essentially the same in all cases.

"There is a significant difference in the percentage of breast cancer events between women who used lipid-lowering drugs and those who did not, and these findings have important public health implications given the widespread use of these medications today," noted Dr. Cauley. "Our findings need confirmation by other, larger studies involving more women and randomized clinical trials before we can recommend therapeutic interventions to prevent breast cancer with these agents."

The hypothesis that reduction in total fat will result in a decreased risk of breast cancer is being tested in a separate study that is part of the Women's Health Initiative (WHI), an ongoing set of clinical trials involving 161,000 women, testing preventive measures for heart disease, osteoporosis and cancer of the breast and colon. Results are expected in 2006. WHI is sponsored by the National Heart, Lung and Blood Institute, one of the National Institutes of Health.


Co-investigators on the current study include other researchers from the University of Pittsburgh, the University of California San Francisco and Kaiser Permanente Center for Health Research in Portland. The study was supported by Public Health Service research grants.

[chubtoad]

http://www.niehs.nih...ews/4brcent.htm

NIH-Funded Centers to Seek Early Environmental Exposures That May Lead to Breast Cancer
National Institutes of Health Director Elias A. Zerhouni, M.D., today announced the funding of four new Breast Cancer and the Environment Research Centers to study the prenatal-to-adult environmental exposures that may predispose a woman to breast cancer.

The centers are funded jointly by the National Institute of Environmental Health Sciences and the National Cancer Institute, both agencies of the National Institutes of Health, at a total of $5 million a year over seven years, or $35 million.

One in eight women in the U.S. can expect to have breast cancer in her lifetime. The causes of most of these cases are not known.

"Although diagnosis and treatment are improving, breast cancer is the leading cancer in women," NIH Director Zerhouni said. "To improve this picture, we need to better understand the elusive environmental piece of the breast cancer puzzle. If we can understand the early events that can set the stage for breast cancer, we can do more to prevent this disease."

The new centers are the University of Cincinnati; Fox Chase Cancer Center, Philadelphia, PA; University of California, San Francisco; and Michigan State University, East Lansing.

They will work collaboratively on several fronts. Using animals, they will study the development of mammary tissue and the effects of specific environmental agents. In the second collaborative project, they will enroll different ethnic groups of young girls and study their life exposures to a wide variety of environmental, nutritional and social factors that impact puberty. Early puberty has been shown to increase breast cancer risk later in life.

The four centers will interact as a single program, though with some specialization at each center. The University of Cincinnati, for example, will explore the factors influencing the decline in age of onset of menstruation in the U.S. and identify improved early markers for cancer susceptibility. They will examine a population of white and African-American students to test the role of diet in the development of adipose tissue and in alteration of hormonal control of sexual maturation. The center will also carry out complementary studies in rodents.

The Fox Chase Cancer Center investigators also plan to study a series of rodent models of mammary gland development. In addition, the researchers will work to understand how environmental exposures may affect the development of puberty in young African-American and Latina girls in East Harlem, N.Y. Such changes in pubertal development may contribute to premenopausal breast cancer, which is more common in African-American women.

The center at University of California, San Francisco, will study the impact of environmental agents on the interactions between epithelial and stromal (connective tissue) cells in normal and cancer-prone mice. An epidemiology study will follow through puberty a multiethnic group of seven- and eight- year-old girls.

Michigan State University researchers will examine environmental exposures that affect the expression and function of estrogen and progesterone receptors in mouse models.

All the centers will work with advocacy groups to add their insight and experience to the research effort. These breast cancer and other advocates also will play a part in outreach activities to translate the results of the research into improved understanding, diagnosis and prevention of breast cancer. These partnerships are unique in breast cancer research.

"Understanding the development of normal mammary tissue is important in understanding what environmental factors might cause susceptibility later in life," NIEHS Director Kenneth Olden said. "These four centers will work in close cooperation, bringing all of their expertise to bear upon these questions. This will be a united effort among the centers, not four centers working in isolation."

NCI Director Andrew von Eschenbach said, "Discovery, development, and delivery are the keys to eliminating suffering and death due to cancer. Our hope is that these new centers will help us discover possible environmental causes of breast cancer so that, based on these discoveries, we can develop and deliver effective treatments to fight this disease. The National Cancer Institute and the National Institute of Environmental Health Sciences will play an active part in managing and supporting these new centers." He noted that October is Breast Cancer Awareness Month, making this an especially appropriate time to announce the funding of the new centers.

[chubtoad]

http://www.washingto...ve/k102303.html


Study pinpoints high rate of cancer among people with genetic mutations; but date of onset can be delayed by exercise and healthy weight in adolescence
Women who carry inherited mutations in the genes BRCA1 or BRCA2 have a lifetime risk of breast cancer of more than 80 percent, as well as a high risk of ovarian cancer, according to the most comprehensive study to date of these women and their families.

The study, published by The New York Breast Cancer Study Group in the Oct. 24 edition of Science, also found that many women with these inherited mutations come from families with few if any reports of breast or ovarian cancer.

The good news from the study is that even among women at very high risk, exercise and healthy weight as an adolescent delayed the onset of breast cancer.

“It was a surprise, but a source of hope, to learn that factors over which we have some control made a difference in the age at which these highest-risk women developed breast cancer,” said the lead author, Mary-Claire King, Ph.D. King is American Cancer Society Professor of Genome Sciences and Medicine in the University of Washington School of Medicine in Seattle and a pioneer in the study of the link between inherited genetic alterations and disease. “Women with inherited mutations were at extremely high risk, but exercise and appropriate weight during their adolescent years clearly delayed the onset of breast cancer.”

“The possibility that lifestyle changes such as increased exercise and weight control could modify the impact of genetic risk has very intriguing implications, not only for BRCA-related cancers but for other breast cancers as well,” said Dr. Larry Norton, head of the Division of Solid Tumor Oncology and Norna S. Serafim Chair in Clinical Oncology at Memorial Sloan-Kettering Cancer Center.

The research was conducted with financial support from The Breast Cancer Research Foundation of New York.

Previous studies had suggested widely varying estimates of breast cancer risk – ranging from 25 percent to 80 percent – among women with BRCA1 and BRCA2 mutations. In order to resolve these discrepancies and accurately calculate risk, the team determined the BRCA1 and BRCA2 genotypes of more than 2,000 people from families each identified through one woman with breast cancer, in the most extensive study of its kind.


What they learned:


Women with the BRCA1 or BRCA2 mutation had a 20 percent chance of developing breast cancer by age 40, a 55 percent chance by age 60, and more than 80 percent by age 80. Overall, they had an 82 percent chance of developing cancer in their lifetime. (The overall risk for all women is about 10 percent.)

The cancer rate varies depending on whether the women were born before or after 1940, the median birth year in the study. This suggests that even when there is a strong genetic risk present, environmental factors play a vital role in determining when cancer occurs. Women born before 1940 had a 24 percent chance of developing breast cancer by age 50; women born after 1940 had a 67 percent chance.

Regardless of what year a woman was born, if she exercised during her teenage years, she was likely to develop cancer later in life than women who did not exercise. That was also true for weight: women who were not obese during their teenage years developed cancer at similar rates, but later in life.

Half the women in the study who carried BRCA1 or BRCA2 mutations and developed cancer did not have a family history of breast cancer. In most cases, that’s because they inherited the mutation from their fathers.
The study involved more than 1,000 women with invasive breast cancer recruited at 12 major cancer centers in the New York City area between 1996 and 2000. The women were Ashkenazi Jewish patients, because the historical demography of this population led to a limited number of different mutations in BRCA1 and BRCA2, facilitating the analysis.

Of the 1,008 index cases with breast cancer, 104 had a mutation in BRCA1 or BRCA2. Exactly 50 percent of these 104 women did not have a history of breast cancer in their immediate family. In nearly all those 52 cases, the mutation had come from the father. “Mutations in BRCA1 and BRCA2 are inherited from fathers as often as from mothers, although fathers are rarely affected with breast cancer. So if a family is small, there may be no warning that a mutation is present,” King said.

"It is appropriate for health-care providers to consider referring breast or ovarian cancer patients for genetic counseling, even if the patient does not have an extensive family history of cancer and particularly if the cancer arises early in life," said Jessica Mandell, certified genetic counselor and the research coordinator of the study. "Genetic counselors can draw upon the results of this study to help women make medical decisions that best suit their and their families' needs related to cancer risk assessment and cancer prevention."

All patients were provided genetic counseling at no cost to them during the study. Co-author Joan H. Marks of the Human Genetics Program at Sarah Lawrence College said the study was unique because "it combined the most current approaches to decoding the information in our genes with the most advanced concepts of psychological counseling and sensitivity toward patients at risk of carrying a breast cancer gene."

The researchers determined the genotypes of adult female relatives of the original breast cancer patients with mutations. The researchers also queried women about environmental factors that might have influenced their breast cancer risk. Of those factors, the ones that appeared protective were normal weight during adolescence as well as exercise (sports, dance, or simply walking a lot). King said researchers should continue to study how environmental factors can modify powerful genetic predispositions toward cancer.

BACKGROUND ON THE BRCA MUTATIONS AND CANCER

Women have about a 10 percent chance of developing breast cancer during their life. Women have about a 1.8 percent risk of developing ovarian cancer, but it’s one of the most deadly cancers.

Between 5 and 10 percent of women who develop breast cancer have inherited a genetic mutation in BRCA1 or BRCA2 that predisposes them to the condition. It’s believed that when BRCA1 and BRCA2 are functioning properly, they help to repair cell damage and prevent cancer. Women whose BRCA1 or BRCA2 genes are affected by mutation thus have an impaired repair mechanism against cancer.

Any woman with a family history of breast cancer is advised to consult a health care provider for a thorough evaluation and careful discussion of all options. Not all women with a family history of breast cancer have an increased risk of developing the condition.

THE BREAST CANCER RESEARCH FOUNDATION

Founded in 1993 by Evelyn H. Lauder, senior corporate vice president of The Estée Lauder Companies, The Breast Cancer Research Foundation is the first and largest organization dedicated to funding clinical and genetic research on breast cancer. Since its inception, the foundation has raised over $70 million for research and awareness. In October 2003, the foundation awarded more than $14.5 million in research grants to 80 scientists at medical institutions across the United States and abroad. More information is available at http://www.bcrfcure.org/.

CLINICAL IMPLICATIONS

The following comments on the clinical implications of the Science paper are from Dr. Julie Gralow, associate professor of medicine in the Division of Medical Oncology at the University of Washington and associate member at Fred Hutchinson Cancer Research Center, and Dr. Elizabeth Swisher, assistant professor of medicine in the Department of Obstetrics and Gynecology, director of the Breast and Ovarian Cancer Prevention Program in the UW School of Medicine and affiliate investigator at Fred Hutchinson. At the Seattle Cancer Care Alliance, Gralow is a breast cancer oncologist and Swisher is a gynecological oncologist.

Both physicians stressed that the findings of the paper are important, but for context it is important to realize that only a small proportion of women in the population have inherited mutations in the BRCA1 or BRCA2 genes. The direct findings of the paper apply only to those women with BRCA1 and BRCA2 mutations.

Most women have a much lower risk of developing breast and ovarian cancer than the women in the study. Most breast and ovarian cancers apparently arise from a complex combination of genetic, lifestyle and environmental factors. Women with BRCA1 and BRCA2 mutations often are diagnosed with breast cancer at a young age, and have a family history of breast and/or ovarian cancer.

This paper shows that women with BRCA mutations have a very high lifetime risk of breast cancer (more than 80 percent) and ovarian cancer (54 percent for BRCA1 mutations and 23 percent for BRCA2 mutations) even when the woman did not have many family members with cancer. This very high cancer risk makes it important to identify those women who have BRCA1 and BRCA2 mutations so preventive measures can be offered, Swisher said.

This is the first time a study has shown that exercise and weight control can influence the onset of cancer in women who have a genetic predisposition to cancer. “Living a healthy lifestyle, getting regular physical activity and maintaining a healthy body weight are important for all aspects of health and well-being in all women, but it is reassuring to know that a healthy lifestyle can help postpone cancer onset in women with a strong inherited predisposition to this disease,” Gralow said.

Another finding of the paper is that many of the women did not necessarily have the strong family history of cancer that tips a woman off that she is high risk. In many of these cases, the mutation came from the father. “There is a misperception out there, even among physicians, that the mutation is always passed down by the mother, but it can also come from the father,” Gralow said.

“It’s very important that a woman try to get as much information as she can about her father’s side of the family when gathering a medical history,” Swisher said. “It’s wise for a woman to ask all her older relatives if they remember anyone in the family with cancer. These questions are becoming more challenging because in the United States, people are now having smaller families, so there are fewer relatives to provide any warning of the mutation.”

Any woman with a family history of two or more breast or ovarian cancers is advised to consult a health-care provider for a thorough evaluation and careful discussion of all options, Swisher said. At places such as the University of Washington/Seattle Cancer Care Alliance Breast and Ovarian Cancer Prevention Program, staff help examine the person’s individual risk assessment, along with lifestyle factors, to determine a prevention and screening plan.

A team of health-care providers – a gynecologic oncologist, surgeon, genetic counselor, medical geneticist, and medical oncologist – may meet with a patient first one-on-one and then all together as a group.

“A multidisciplinary team like this can help each woman develop a plan to lower and manage her risk for breast or ovarian cancer,” Swisher said.

There are a number of ways that women with a genetic risk of breast and ovarian cancer can decrease cancer risk. Women may participate in aggressive monitoring programs that try to detect any cancer as soon as possible. A number of medications to prevent cancer (such as tamoxifen) are being evaluated in high-risk women. Surgery to remove the ovaries can reduce the risk of both breast and ovarian cancer. Risk-reducing prophylactic breast surgery is another option for women at extremely high risk of breast cancer.

[kevin]

Link: http://cme.ucdmc.ucd...R/reversed.html
Date: 11-20-03
Author: -
Source: UCDavis
Title: BREAST CANCER CAN BE REVERSED IN LABORATORY MICE, SCIENTISTS REPORT

---

CONTACT: Claudia Morain
UC Davis Cancer Center
Pager: (916) 762-9855
BREAST CANCER CAN BE REVERSED IN LABORATORY MICE, SCIENTISTS REPORT
Findings provide new molecular drug targets, validate transgenic mouse models

(SACRAMENTO, Calif.) — Breast cancer researchers have demonstrated for the first time that it is possible to block genetic switches in mice that turn cancer on and off — thus preventing and even reversing breast cancer in the animals. The findings, reported Sunday morning at the 24th Congress of the International Association for Breast Cancer Research, suggest potential new molecular targets for drugs to prevent and potentially eradicate breast cancer in humans.

“It’s enormously gratifying,” said conference director Robert Cardiff, professor of pathology at UC Davis School of Medicine and Medical Center and an author of the research. “Our findings suggest paths forward that may help us alter the biological path of breast cancer and more successfully treat — and even potentially prevent — this cancer in humans.”

In new research reported by a team of scientists from Canada, Switzerland and UC Davis, investigators demonstrated that removing a single gene known as beta-1 integrin prevented or halted breast cancer growth in laboratory mice. Beta-1 integrin is a principal regulator of normal breast tissue growth and survival, but if the gene malfunctions, it can directly initiate breast tumors. The new work demonstrates that knocking out the beta-1 integrin gene prevents cancer-prone mice from developing breast tumors, and halts further tumor growth in mice that have already developed breast cancer.

“This study shows that it is absolutely essential to have the beta-1 integrin gene present in order for mammary gland tumors to develop. We now have a good target for biological drug development, and the challenge is to develop an agent that can block its activity,” said William J. Muller, professor of biochemistry at McGill University in Montreal and a lead investigator of the study.

In a related presentation, researchers from the University of Pennsylvania reported on a series of experiments using a novel mouse model of human breast cancer, one that enables scientists to turn oncogenes — genes that can cause cancer — on or off at will. A triggering agent, in this case the antibiotic doxycycline, throws the switch on or off. Scientists used the approach to test four oncogenes: c-myc, Neu, Wnt1, and v-Ha-Ras. When any one of the oncogenes was turned on, the transgenic mice developed extremely aggressive mammary tumors; in many cases, the tumors metastasized to the lungs. When the gene was turned off, many of the breast tumors — including many of the most aggressive and advanced cancers — regressed to the point that they no longer could be detected by physical examination, magnetic resonance imaging (MRI) or positron emission tomography (PET) scans.

“We’re extremely encouraged that we have been able to demonstrate in laboratory animals that we can make mammary cancers essentially disappear by reversing just one mutation,” said Lewis A. Chodosh, associate professor at the Abramson Family Cancer Research Center at the University of Pennsylvania and lead author of the study.

“This suggests that, with appropriate therapies that target the genes used in this study, we might be able to cause tumors to regress and improve substantially, even those that are quite advanced.”

However, even though many of the tumors in the transgenic mice went into complete remission, a substantial number of the cancers spontaneously recurred over periods of up to a year, Chodosh reported.

This finding is important since it replicates the natural history of human breast cancer — many women, after apparently successful treatment, harbor residual tumor cells that eventually give rise to tumor recurrences that ultimately may result in death. Some of these residual cells can remain for decades. No previous laboratory mouse model has successfully replicated this feature of human breast cancer cells.

“The next critical step is to figure out the mechanisms that some tumors use to escape these treatments,” Chodosh said. “We believe these mouse models will help us to do exactly that.”

Founded in the mid 1950s, the International Association for Breast Cancer Research is an international community of scientists focused on the important issues in modern breast cancer research. The 24th IABCR Congress, focused on preclinical research using mouse models of human breast cancer, is sponsored by UC Davis Cancer Center, the Office of Women’s Health of the U.S. Department of Health and Human Services, the California Breast Cancer Research Program, and the National Cancer Institute’s Mouse Models of Human Cancers Consortium and Specialized Programs of Research Excellence.

For more information about the meeting, visit the conference Web site at http://cme.ucdmc.ucdavis.edu/iabcr.htm.


# # #

Copies of all news releases from UC Davis Cancer Center are available on the Web at http://news.ucdmc.ucdavis.edu

[chubtoad]

http://www.scienceda...31121070843.htm
Source: University Of Minnesota
Date: 2003-11-24

Imaging Technique May Diagnose Breast Cancer Without Biopsy

MINNEAPOLIS / ST. PAUL -- A technique that combines high-level magnetic resonance imaging (MRI) with a new spectroscopic method may result in an accurate, non-invasive way to make breast cancer diagnoses. In this technique, MRI is used to detect breast lumps, while spectroscopy measures molecules known to accumulate in cancer cells.

According to a study in the Nov. 21 online version of the journal Magnetic Resonance in Medicine, researchers at The Cancer Center at the University of Minnesota have developed a magnetic resonance spectroscopy (MRS) method that quantifies breast tissue levels of choline (tCho) compounds, which the study found to be elevated in malignant lesions. Previous investigations of the diagnostic utility of MRS did not quantify tCho levels in breast masses, which limited the ability to differentiate between benign and malignant lumps detected by MRI.

"We found tCho concentrations to be significantly higher in malignancies than in benign lumps and normal breast tissues using this quantitative method," said lead investigator Michael Garwood, Ph.D., professor of radiology and Cancer Center member. "Using high magnetic fields and this spectroscopic technique may produce a powerful way to diagnose breast cancer and to monitor its response to treatment. We hope this technique will eventually be used to avoid unnecessary biopsy."

The application of MRS to breast cancer has unique technical demands. The problem lies in the composition of the breast, whose irregular distribution of fatty and glandular tissue makes it difficult to establish reference points against which to measure tCho levels. This method accounts for these tissue variations, using water as a reference compound and a mathematical approach to help "fit" or see choline levels relative to other compounds. This technique also exploits the increased sensitivity of a high magnetic field MR scanner, available only at a few locations in the world, including the University of Minnesota's Center for Magnetic Resonance Research (CMRR).

So far the study has enrolled 105 subjects and measured tCho levels in normal breast tissue and in benign and malignant lesions. The study remains open to women who have a suspicious breast lump; however, MRI and MRS scanning must occur before a biopsy or surgery on the lump has been performed. To determine the accuracy of the test, tCho concentrations will be compared with the pathologic findings in the excised tissues. Women interested in participating in the study can call 612-273-1944.

[chubtoad]

http://www.scienceda...31212074727.htm
Source: Johns Hopkins Medical Institutions
Date: 2003-12-12

Combining Various Magnetic Resonance Imaging Techniques May Help Improve Breast Cancer Detection

Researchers at Johns Hopkins say that combining various types of magnetic resonance (MR) imaging techniques more accurately sorts cancers from benign masses in breast tissues than any single imaging techniques. Their findings are presented in the October issue of Radiology.

Magnetic resonance imaging scanners can be calibrated to take images that highlight a specific type of human tissue. For example, so-called T1-weighted imaging sequences are best at imaging fatty tissues, while T2-weighted sequences best show fluids, like those found inside cysts. Additionally, 3-dimensional MR imaging can help define the size and shape of tumors. Contrast agents, dyes injected into patients prior to imaging to concentrate in the tumor and make it more visible, further enhance MR images similar to the way dye in water helps highlight the "veins" in celery stalks.

In their study, Hopkins researchers combined T1, T2 and 3-D imaging techniques, with and without contrast agents, on 36 subjects. Eighteen already had been diagnosed with benign breast lesions, and 18 with breast cancer. The researchers reviewed the results of the combined images without knowing which images came from which patient.

The combined, or multiparametric MRI technique, was able to identify and characterize breast lesion tissue clusters in all 36 patients, revealing which were benign and which were malignant. In addition, the multiparametric technique was even more powerful when used with contrast agents, providing more precise differentiation between the cancerous and non-cancerous tissue than the same images without contrast.

"Each individual imaging modality has its advantages," says Michael Jacobs, Ph.D., the lead researcher for the study at the Hopkins Department of Radiology. "When all these techniques are combined into one data set, you can achieve an approach that shows the characteristics of a lesion not normally available using just one imaging technique."

Jacobs notes that while his study appears to demonstrate the feasibility of using a combined imaging approach to identifying breast tumors, larger studies are needed to determine if the approach might be useful for studying the molecular dynamics of breast cancer tumors.

"It's known that certain compounds, such as choline and sodium ions, tend to concentrate in cancer cells," Jacobs says. "We are now investigating whether multiparametric MR imaging might be effective in imaging intracellular compounds within breast tumors. If so, this will enable a comprehensive assessment of the tumor environment."

[chubtoad]

http://www.scienceda...31223065655.htm
Source: Journal Of The National Cancer Institute
Date:
2003-12-26

Oral Drug Showing Promise For Breast Cancer Prevention In A Mouse Model
The oral drug ZD1839, also known as gefitinib, prevented the development of estrogen receptor (ER)-negative breast cancer in a mouse model, which raises the possibility that the drug could be a preventive agent for ER-negative breast cancer. The results appear in the December 17 issue of the Journal of the National Cancer Institute.

ER-negative breast cancers are not dependent on estrogen to grow and do not respond to antiestrogen drugs such as tamoxifen and raloxifene. ZD1839, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, blocks the cellular signaling pathway that contributes to tumor survival and growth, and studies have shown that ZD1839 is effective at inhibiting the growth of various types of cancer cells, including breast cancer cells.
To test whether ZD1839 can inhibit the growth of ER-negative breast cancer cells, Chunhua Lu, M.D., Ph.D., and Powel H. Brown, M.D., Ph.D., of the Baylor College of Medicine in Houston, and their colleagues treated ER-negative normal, immortalized (i.e., precancerous), and cancerous breast cells with ZD1839. They also examined the effect of ZD1839 on the development of ER-negative breast tumors in transgenic mice.

Treatment with ZD1839 suppressed the growth of ER-negative normal, immortalized, and cancerous breast cells. Moreover, ZD1839 treatment of transgenic mice that normally develop breast tumors in approximately 230 days delayed the formation of ER-negative tumors to more than 310 days. ZD1839 also reduced proliferation of normal breast cells by 20.3% and of tumor cells by 42%.
In an accompanying editorial, Dennis J. Slamon, M.D., Ph.D., of the University of California at Los Angeles Jonsson Comprehensive Cancer Center, and his colleagues commend the new findings, but caution that long-term safety data are not available for ZD1839. They point out that some patients taking ZD1839 for non–small-cell lung cancer have developed interstitial lung disease, a rare but potentially dangerous side effect, particularly if ZD1839 is used as a chemopreventive agent in healthy women.

In addition, they say, the effectiveness of ZD1839 and other EGFR inhibitors may be limited to a subpopulation of patients in whom EGFR is involved in tumor formation or growth. "Before we develop gefitinib as a chemopreventive agent, further research is needed to find and validate predictive factors that can be used to identify patients and healthy women likely to respond to gefitinib as a therapeutic and chemopreventive agent," they conclude.

[chubtoad]

http://www.scienceda...40116074620.htm
Source: European Space Agency
Date: 2004-01-16

Space Technology In New Technique To Fight Breast Cancer

A novel non-invasive system for cancer treatment is being developed with technology from the European space industry. The first target for this new treatment, which could be ready as early as 2006, is breast cancer.

Results Reported For New Breast Cancer Therapy

Initial Results Promising For MIT Breast Cancer Treatment

Dutch entrepreneur Hugo Brunsveld van Hulten has come up with a solution to help physicians in their fight against breast cancer that combines two techniques: magnetic resonance imaging (MRI) to locate and diagnose cancerous tissue and high-intensity focused ultrasound (HIFU) to 'burn' malignant cells.

This invention, named ActiveFU, is being developed by Brunsveld van Hulten at the new European Space Incubator (ESI) facility at ESTEC, ESA’s European Space Research and Test Centre in the Netherlands. By using space technologies and expertise from ESA's space research teams several challenges have already been overcome.

"HIFU is a proven intervention technique for the ablation of cancer cells in the human body," explains Brunsveld van Hulten. "This technique combined with the recent advances in MRI capabilities that can provide a proper real-time view of the area during treatment, will give the ActiveFU operator highly-sophisticated control of the hyper-thermal tumour-targeting procedure".

This innovative system will offer cancer patients a new non-invasive treatment option that is more patient-friendly and without the negative side effects associated with chemo and radiation therapies.

"Benefits will also include savings to the public health care sector because it is an outpatient treatment," adds Brunsveld van Hulten.

Originally a mathematician, Brunsveld van Hulten started working in remote sensing but since the early nineties he has been involved in the use of MRI to carry out biopsies for breast cancer and in studying the use of ultrasound for medical treatment.

"I got the idea when I looked into the MRI market, which today is still limited to diagnostics. I could see that the logical next step for the use of MRI would be for interventional therapy," explains Brunsveld van Hulten. “I came to the conclusion that the use of a dedicated HIFU system with a quality imaging MRI-breast-coil - the device that actually generates the image - could be a major breakthrough."

"The chosen imaging coil also allows for non-invasive MRI diagnostics or performance of magnetic resonance spectroscopy for chemical analysis and biopsies for pathology, which completes a competitive toolset for diagnostics and intervention in the MRI room."

To gain another competitive advantage, Brunsveld van Hulten selected a breast coil compatible with the latest 1.5-Tesla and 3-Tesla systems with higher acquisition rates and improved resolution recently put on the market by the three major MRI scanner suppliers: General Electric, Siemens and Philips.

His new technique can be used to treat any small and localised tumours but Brunsveld van Hulten has chosen to focus initially on treating breast cancer, as this is one of the most prevalent forms of cancer particular affecting women between 35 to 69 years of age.

Help from ESA expertise under ESI umbrella Many pieces still have to fall into place before patients can be cured, which is why the use of the European Space Incubator (ESI) facility at ESTEC, and the support of ESA's engineers and medical experts, are so important.

"ESA's capacity to simulate complex systems has been vital in determining the optimal materials and technologies to use," says Brunsveld van Hulten. The software platform EuroSim - originally developed for ESA to simulate in real time the behaviour of satellites - was used to help solving the engineering complexities of designing the system.

Although much of the hardware is industrial standard, Brunsveld van Hulten emphasises that "it was the electronic circuits and embedded software from ESA that enabled me to develop a system for real-time simulation and control of the critical thermal treatment process – unique benefits obtainable from applying space technologies to this already advanced medical product."

ESA's expertise in wave propagation modelling has been essential in getting the two MRI and HIFU technologies to work optimally together. The modelling allows a fast simulation of the ultrasound transducer settings to inspect the effects prior to actual treatment.

Usually the magnetic resonance imaging is disturbed by the ultrasound therapeutic system, but Brunsveld van Hulten has managed with the help from ESA's experts to adjust signal frequencies and phases in such a way that a physician using ActiveFU can perform the intervention and at the same time follow the result by MRI.

Miniature non-magnetic piezo motors are used to position the equipment before intervention. Cedrat Technologies originally developed these for space applications where no disturbance of the homogeneous magnetic field for imaging can be accepted.

In December, ESA’s Concurrent Design Facility (CDF) was used to adjust and fine-tune the technical requirements for the components of this complex project. Specialists from different technical disciplines participated in a number of CDF sessions where they interactively ‘negotiated’ the requirements of their respective sub-systems. This dynamic process quickly highlights and eliminates conflicts already in the system at top-level design.

In addition to the support obtained from ESA’s in-house medical expertise, ESI also assisted Brunsveld van Hulten by organizing an international workshop, under the auspices of ESA, to consult outside leading medical experts. The participants discussed user requirements and operational constraints as well as the new non-invasive diagnostic methods used by the rapidly developing MRI technology.

ActiveFU is the first product to emerge from ESI. Bruno Naulais, ESI manager reports, “Our experience with the ActiveFU project has demonstrated that ESI can bridge the gap between having an idea and starting up an actual business. It supports entrepreneurs such as Brunsveld van Hulten to build a viable business plan, to conduct feasibility studies on the technology to be used, and to bring the project to a level where venture capital is attracted to co-finance its further development."

[chubtoad]

http://www.scienceda...40302075632.htm
Source: Johns Hopkins Medical Institutions
Date: 2004-03-03

New Imaging Technique Developed To Identify Breast Cancer

Researchers at Johns Hopkins have for the first time used a chemical marker detected by proton magnetic resonance spectroscopic imaging (MRSI) to successfully diagnose breast cancer. The diagnostic technique produces pictures of choline within breast tumors.

In the study, researchers from the Russell H. Morgan Department of Radiology and Radiological Science at Hopkins demonstrated that choline signals analyzed by MRI were significantly elevated in malignant tumors in 15 of 18 patients studied. Three of the cases could not be included because of technical failures such as patient movement or computer failure during the scanning procedure.

The results are published in the December-January issue of the Journal of Magnetic Resonance Imaging.

Scientists have long known that cancers contain elevated levels of choline, a product of membrane synthesis, but the Hopkins study is believed to be the first to demonstrate its value in accurately identifying breast tumors.

MRSI of the breast does not appear likely to be cost-effective as a routine screening tool for breast cancer, but may prove to be a viable, noninvasive alternative to biopsy in cases with positive mammography or clinical breast exam results, says Michael A. Jacobs, Ph.D., the lead researcher for the Hopkins study. "What MRSI does provide is information about the molecular environment of breast tumors, which also may be useful in designing therapeutic interventions for patients."

Proton magnetic resonance imaging uses the water content in tissue to produce images by measuring signals emitted after subjecting the tissue to high magnetic fields, but provides no information on the chemical or molecular aspects of the tissue being imaged. Combining proton MRI with spectroscopy allows the scientists to differentiate intracellular components of the cell and signals emitted by certain biochemicals, such as choline.

In the study, 15 patients who had been referred for MRI evaluation after previous examination had revealed breast tumors underwent regular breast MRI to identify the lesion. These studies were followed by MRSI scanning to determine if choline signals in the tumors could be adequately imaged using spectroscopy. Biopsies performed after the imaging revealed that eight of the tumors were malignant carcinomas and seven were benign. MRSI showed elevated choline levels in all eight of the malignant tumors.

"These data are proof of principle, and strongly suggest that MRSI can serve as an important adjunct to the routine MRI scan that may aid physicians in making a diagnosis of breast cancer," says Jacobs. "We can envision a time when this procedure may even replace the need for biopsy in some cases and provide the basis to follow treatment strategies in certain cases of breast cancer. However, more research is needed to fully understand the potential impact of these findings."

[chubtoad]

http://news.bbc.co.u...lth/3558641.stm
Tuesday, 23 March, 2004

Vitamin D may fight breast cancer

Scientists at Birmingham University and St George's Hospital, London, found breast tissue contains an enzyme that activates vitamin D.

Levels of the enzyme were elevated in breast tumours - suggesting the vitamin is produced to try to combat the spread of cancer.

The research was presented at a meeting of the British Endocrine Societies.

  Perhaps now it's time to look at improving our dietary intake through fortification of more foods with Vitamin D.

Dr Martin Hewison 
Previously it was thought that the active form of vitamin D - calcitriol, which is a potent anti-cancer agent, was only made in the kidney.

The researchers think having a local cancer-fighting 'factory' is part of the breast's natural immune response to a tumour.

And they suggest that the rise in breast cancer rates in the UK may be linked to the fact that we have low levels of vitamin D in our bodies.

Exposure to sunlight is the greatest source of vitamin D and population studies have previously suggested higher vitamin levels may contribute to the lower incidence of breast cancer seen in sunny climates such as the Mediterranean.

Diet possibilities

Lead researcher Dr Martin Hewison said: "Our work shows that the breast has its own local 'factory' for generating the anti-cancer form of vitamin D.

"Unfortunately women who live in cloudy countries like the UK may not have enough of the raw material, vitamin D, to fuel this factory.

"Exposure to sunlight is the most efficient way of generating vitamin D in our bodies, but we all know of the dangers of sunbathing.

"Perhaps now it's time to look at improving our dietary intake through fortification of more foods with Vitamin D."

Delyth Morgan, of the charity Breakthrough Breast Cancer, said previous research had also suggested that vitamin D may help prevent and treat some cancers, including breast cancer.

However, she said the effect had yet to be confirmed in human trials.

"Further research is needed before any firm conclusions about the role of vitamin D in breast cancer prevention can be established."

Vitamin D is generated by exposing the skin to sunlight. It is also found in dairy products, fish oils and breakfast cereals.

However, too much vitamin D is thought to disrupt the body's phosphate and calcium levels.

The UK Food Standards Agency recommends a daily allowance of 5 micrograms.

[chubtoad]

http://www.wi.mit.ed...uperwasser.html
March 22, 2004

Study Offers New Model For Breast Cancer

The last few years have witnessed critical advances in breast cancer therapies. Still, the disease afflicts one in eight American women, and scientists have yet to develop a living model with which they can study the intricacies of human breast-tumor behavior.

Now, a team in the lab of scientist Robert Weinberg at Whitehead Institute for Biomedical Research has successfully grafted human breast tissue into the mammary glands of mice. As a result, the mice formed functional breasts that are capable of producing human breast milk. More importantly, some of these mice were engineered to form early stage breast tumors like those found in humans.

“This is the first experimental model of human breast cancer in the mouse that we’ve ever had,” says Charlotte Kuperwasser, lead author of the study and a former postdoctoral researcher in the Weinberg lab who now is an assistant professor at Tufts University School of Medicine. The study appears online this week in the early edition of the journal Proceedings of the National Academy of Sciences.

Currently, researchers studying human breast cancer tissue must rely on biopsies on slides for their work, an effective technique in many respects, but one that doesn’t allow scientists to view the tumors in action. Alternatively, they may propagate human breast cancer cells in culture. Attempts to create live models by injecting human cancer tissues beneath the skin of mice have been ineffective because the cancer cells used in these experiments typically are bred in Petri dishes and end up bearing little resemblance to human cancer. In addition, these tumor cells often stop growing after they’ve been injected.
[...]
These mice also may prove highly effective for testing potential breast cancer drugs. Because the tumors in the mice have developed naturally, results from such clinical trials most likely would provide a highly predictive indicator of how these drugs would behave in people. Kuperwasser is currently consulting with pharmaceutical companies who are developing breast cancer therapies. Meanwhile, Whitehead has filed a patent for this procedure.

The next step is to take advanced human breast cancer tissues from patients and incorporate them into these mice to see if the cancer continues to develop as it does in humans. “If so,” says Kuperwasser, “then we’ll really have a powerful model and tool to study both the development of cancer and how the tissue environment affects its behavior.”

[chubtoad]

http://www.brighaman...er_03_10_04.asp

Low Caloric Intake Associated with Reduced Breast Cancer Incidence
Study suggests that diet during early life may play a role in breast cancer development

BOSTON - Researchers from Brigham and Women's Hospital (BWH) have successfully tested in humans a long-standing observation made in the animal model: that restricting caloric intake could help reduce the risk of breast cancer. The study, conducted in collaboration with researchers from Stockholm, Sweden, also found that low caloric intake among women who go on to have children appears to be associated with an even more pronounced reduction in risk. The study will appear in the March 10, 2004 issue of the Journal of the American Medical Association.

Breast cancer is the most common form of cancer in women and second leading cause of cancer death among women in the United States, with one in eight women faced with the risk of developing breast cancer in her lifetime. The number of new cases of breast cancer has increased by one percent per year in the United States since the 1940s.

According to lead author Karin B. Michels, ScD, MSc, MPH of BWH and associate professor at Harvard Medical School (HMS), “These scientific findings are encouraging as they will help researchers better understand the underlying physiology responsible for breast cancer development. Our observations indicate that breast cancer may originate during the early phases of a woman’s life, from puberty to early adulthood, and that diet during this phase may be important to reduce future risk of breast cancer.”

Prior to beginning this study, Michels and her colleague Anders Ekbom, MD, PhD, professor at Karolinska Hospital, Sweden, hypothesized that reduced caloric intake during adolescence or early adulthood would provide breast health benefits. Their assumption was based on findings made repeatedly in rodents: restricting caloric intake is one of the most effective ways to reduce cancer incidence and extend lifespan in the animal model. Since such experimental conditions cannot be applied to humans, a model had to be found to mimic caloric restriction in humans. Hence, this epidemiologic study targeted a population of 7,303 women from the Swedish Inpatient Registry who severely reduced caloric intake while suffering from severe anorexia nervosa prior to age 40, between the years 1965 and 1998. Information on these women was cross-referenced with the Swedish Fertility Registry that has information on every birth in Sweden since 1924 and the Swedish Cancer Registry, which registers all new cancer cases in Sweden.

[chubtoad]

http://www.scienceda...40329074633.htm

Catalase (CAT) genotype, dietary antioxidants, and breast cancer risk

In the first study ever to evaluate catalase (CAT) genotypes and breast cancer, researchers at Roswell Park Cancer Institute in Buffalo, N.Y., found that women with the most common genotype for reducing oxidative stress are at a reduced risk of developing breast cancer. Further, they can diminish their breast cancer risk even more by including ample fruits and vegetables in their diets.

Fruits and vegetables are well known to reduce the risk of some cancers through their antioxidant properties; that is, by inhibiting reactive oxidant species. These free radicals form naturally in the course of cell respiration and metabolism, but have been linked with disease-causing damage to tissue and changes in DNA that can lead to malignancies.

While this oxidative stress is considered to be a major causative factor for breast cancer, prominent research including the Nurses Health Study has shown no link between increased consumption of fruits and vegetables and decreased breast cancer risk. Because the evidence on whether fruits and vegetables reduce the risk of breast cancer is not clear, the investigators from Roswell Park thought that effects might be limited to women with specific genotypes related to protection from oxidative stress.

Jiyoung Ahn, M.S., R.D., a pre-doctoral research associate in the department of epidemiology at Roswell Park, and a Ph.D. student in the division of nutritional sciences at Cornell University, considered the fact that catalase (CAT) is one of the most effective enzymes in the body for reducing oxidative stress. It converts hydrogen peroxide into water and oxygen, thus neutralizing reactive oxygen species. Ahn wondered if higher levels of the endogenous antioxidants that course through the human blood stream naturally - like those resulting from the CAT C (CC) allele - might provide some degree of antioxidant protection against breast cancer, and if the risk might be further diminished by the consumption of fruits, vegetables and specific antioxidants.

Working with her academic advisor, Christine Ambrosone, Ph.D., chair of the Roswell Park department of epidemiology, Ahn evaluated this hypothesis in a population-based, case-control study of 1,037 women with breast cancer and 1,086 healthy subjects in Nassau and Suffolk Counties, N.Y., conducted originally by Marilie Gammon, Ph.D., and colleagues. Each woman was interviewed at home to assess suspected breast cancer risk factors over the course of her lifetime, and administered the Block food frequency questionnaire to determine dietary intake the preceding 12 months.

The women were genotyped, with the most common genotype the CAT C (CC), present in a little more than 60 percent of the cases and the controls. A CT polymorphism exists in the (CAT) gene in about 33 percent of participants, and all others - some four percent - have the TT genotype.

Women with the CC genotype and a diet rich in fruits and vegetables had a 30 percent reduced risk of breast cancer. There was only a five percent lower risk in women with the CC genotype who ate very few fruits and vegetables.

"With so many women having the CC genotype," said Ahn, "our study potentially has a very important public health impact. Of course, none of us knows our exact genetic make-up, but since eating a diet high in fruits and vegetables is known to contribute to a healthy lifestyle anyway, women can consider it a viable means of reducing their breast cancer risk, as well."

[chubtoad]

http://www.nature.co...9/040329-2.html
Food chemical may pose little risk to humans.
30 March 2004
MARK PEPLOW

No link between acrylamide and breast cancer

Eating food that contains acrylamide, a probable human carcinogen, does not seem to increase the risk of breast cancer. The results, from a Swedish study involving 50,000 women, were announced at the American Chemical Society's annual meeting in Anaheim today.

"The [average] acrylamide intake for those who develop breast cancer is the same as for those who don't," says Lorelei Mucci, an epidemiologist from the Harvard School of Public Health, Boston, who led the research. She completed a similar study last year showing that acrylamide does not increase levels of bowel, kidney or bladder cancers1.

The chemical is formed when food containing sugars and amino acids is heated above about 120 °C during frying or baking. They combine in a well-known process called the Maillard reaction, producing acrylamide and other by-products. The same reaction produces the brown crust on baked bread.

Acrylamide caused a public-health scare in 2002 when a Swedish study found the chemical in products ranging from chips to biscuits at levels higher than the World Health Organization recommends for drinking water2.

Prunes to crumpets

On Friday, the US Food and Drug Administration announced that it had found acrylamide in olives, prune juice and teething biscuits.

Other researchers at the American Chemical Society meeting revealed that gingerbread contains high levels of the chemical, whereas naan bread, crumpets and fruitcake apparently contain less than do other bread products. Gingerbread had lower levels of acrylamide when citric acid was included in the mix.

But Mucci says that epidemiologists and toxicologists are now beginning to conclude that acrylamide in food presents little risk to humans. "No one is saying this will cause an epidemic of cancer," she says.

Acrylamide was classed as a probable human carcinogen on the basis of toxicology tests on animals. But these tests involved huge doses of pure acrylamide, rather than smaller quantities in food, explains Richard LoPachin, who studies the effects of acrylamide on rat brains at the Montefiore Medical Center in New York City.

He says that the effects of acrylamide on our brains are still poorly understood, and that more research is needed to discover whether decades spent eating foods high in acrylamide could lead to nervous system disorders. Industrial workers exposed to high levels of acrylamide can develop symptoms including sweating, peeling skin and muscle weakness, he says.

[chubtoad]

http://www.scienceda...40331005515.htm

Minimally Invasive Breast Cancer Treatment Shows Promise

A pilot study using radiofrequency (RF) ablation to treat small breast cancers has found the procedure feasible and safe, according to an article appearing in the April issue of the journal Radiology.

"This study has added another potential weapon to the breast cancer treatment arsenal," said the study's lead author, Bruno D. Fornage, M.D., who is a professor of radiology and surgical oncology at The University of Texas M. D. Anderson Cancer Center in Houston.

RF ablation treats tumors with heat produced by an electrical current. Ultrasound imaging is used to guide a needle-electrode to the tumor's center, where a temperature of approximately 200º F is applied for 15 minutes to destroy malignant tissue.

To determine the feasibility and safety of RF ablation in the treatment of small breast cancers (2 centimeters or less in diameter--about the size of a grape), the researchers performed RF ablation on 21 breast cancers in 20 patients immediately before the patients underwent surgical lumpectomy (removal of the breast tumor and a small amount of surrounding tissue) or mastectomy (removal of the breast). After surgical excision, the specimens were evaluated by a pathologist to confirm whether RF ablation had eliminated all cancerous cells.

In all 21 cases, the target tumor that was seen on ultrasound was completely ablated with no adverse effects. In one of two patients who had received preoperative chemotherapy to shrink the tumor, residual microscopic cancer that did not show up on imaging was found around the ablated target.

Although the results of the feasibility and safety study were positive, this minimally invasive procedure is currently limited as a treatment because surrounding tissue is not removed from the tumor site with ablation. Therefore, physicians cannot test the tissue to be certain all cancer has been destroyed.

"This is an experimental study, and additional long-term trials will be needed before RF ablation becomes available as an alternative to surgery in the treatment for early breast cancer," Dr. Fornage said.

[chubtoad]

http://www.mdanderso...0fb00508b603a14

Longevity Gene May Also Predict Better Outcome for Breast Cancer Patients

M. D. Anderson News Release 04/15/04
A gene known to promote longevity in animals has now been discovered to encode a tumor suppressor – a protein that helps prevent cancer, according to a study by a team of scientists from The University of Texas M. D. Anderson Cancer Center. The new gene, which was inactivated in two-thirds of patients studied, presents a potent new target for breast cancer therapy, the researchers say.

In a study published in the April 16, 2004, issue of the journal Cell, scientists describe how the presence of the protein, named Forkhead box class O3 (FOXO3), is associated with better outcomes for breast cancer patients. Conversely, if FOXO3 was inactivated, patients had worse outcomes.

“This is a very good prognostic marker for breast cancer patient outcome,” said Mien-Chie Hung, Ph.D., the co-principal investigator of the study. “In addition, these proteins provide new targets for cancer therapy and prevention.”

The research team, which was a collaboration between the laboratories of Mickey C.-T. Hu, Ph.D., and Hung, both of the Department of Molecular and Cellular Oncology at M. D. Anderson, demonstrated that FOXO3 is inactivated in many cancer patients by an enzyme called IKK and determined that IKK is an oncoprotein, a protein that can induce cancer.

“We have uncovered two important events and put them together in one story,” says Hung. “This research has identified an important new tumor suppressor protein and a new oncogene that provide targets for cancer therapy. Previously, these proteins had been suspected to be involved in cancer, but there was no direct evidence for that.”

The IKK oncoprotein belongs to a family of enzymes called kinases. Researchers have shown that blocking certain kinases can be an effective way to block cancer. New generation cancer drugs such as Gleevec, which has been effective in treating leukemia patients, work by zeroing in and inactivating a kinase molecule. Such targeted therapies are designed to kill cancer cells while avoiding serious damage to other, non-cancerous cells.

The scientists discovered the protein’s role in cancer while studying how normal cells can turn cancerous. They showed that IKK can attach to the FOXO3 protein and inactivate it. When the normal function of FOXO3 is blocked, the cell can multiply unchecked.

Once they had established that inactivated FOXO3 protein could lead to cancer, the researchers examined its role in tumor cells from 131 breast cancer patients. They found FOXO3 in 113 out of 131 samples. Of the 113 samples with FOXO3, the protein was inactive in 83 and active in 30 samples. When they looked at patient survival, they found a strong correlation between active FOXO3 and better patient survival. Additional research revealed the FOXO3 protein can be found in patients with stomach, liver and lung cancer. However, the scientists did not study enough of these patient samples to say how important the gene is in these cancers.

In additional laboratory studies, the scientists demonstrated that a slightly altered form of FOXO3 that can’t be inactivated by IKK acts as an even more potent tumor suppressor than the normal FOXO protein.

“This mutant FOXO3 may be an even more powerful tumor suppressor than the normal FOXO3 protein,” says Hung. “This finding may provide a new avenue for cancer gene therapy or other targeted cancer therapies.”

The presence of active Forkhead (FOXO) protein has been linked to longevity in laboratory animals such as the nematode worm, says Hung. Hu and Hung’s discovery that FOXO3 is a tumor suppressor may provide a clue to the gene’s ability to increase lifespan in animals. But exactly how a tumor suppressor could increase lifespan remains a mystery.

“That is the million-dollar question,” Hung says.

[chubtoad]

http://web.mit.edu/n...eastcancer.html

MIT aims radar research at breast cancer

CAMBRIDGE, Mass. -- A breast cancer treatment based on MIT radar research that was originally intended to detect space-borne missiles is showing promise in the final phase of clinical testing.

Preliminary results to be presented on Wednesday, April 21 at the 9th International Congress on Hyperthermic Oncology in St. Louis show that women with early-stage breast cancer who received the MIT treatment prior to lumpectomy had a 43 percent reduction in the incidence rate of cancer cells found close to the surgical margins. This is important because additional breast surgery and/or radiation therapy are often recommended for patients that have cancer cells close to the edge of the lumpectomy surgical margin.

"One of the primary objectives of this randomized study is to demonstrate that heat can affect and kill early-stage breast cancer cells prior to surgery," said William C. Dooley, director of surgical oncology at the University of Oklahoma Breast Institute and principal investigator of the ongoing study. "With this focused heat treatment, it may be possible for the surgeon to provide better margins for the patient and possibly avoid additional treatment procedures and avoid recurrence of the cancer."

Since October 2002, 90 women with early-stage breast cancer have enrolled in the study, in which microwave energy focused externally on the breast is delivered to tumors prior to lumpectomy. The goal is to use focused heat to kill tumor cells and reduce additional surgery. The current results are based on the 64 women who have completed the study.

Treating cancer with heat is not a new idea, but "researchers were having trouble using it to treat tumors deep within the body," said Alan Fenn, a senior staff member at MIT Lincoln Laboratory and inventor of the technique. Further, it's difficult to deliver the heat only to cancer cells and not overheat normal tissue.

The microwaves in the new technique "heat -- and kill -- cells containing high amounts of water," he said. Cancer cells have a high water content (around 80 percent), while healthy breast tissue contains much less.

The outpatient procedure uses a single tiny needle probe to sense and measure parameters during treatment. Side effects appear to be minimal.

Patients in the thermotherapy group of the current study receive a minimally invasive heat treatment prior to surgery and radiation therapy, while patients in the control group receive surgery alone prior to radiation therapy. Preliminary results indicate that in the thermotherapy group, 5 of 30 (16.7%) patients had tumor cells close to the surgical margins, whereas in the group receiving surgery alone, 10 of 34 (29.4%) patients had tumor cells close to the margin.

[chubtoad]

http://www.scienceda...40503054054.htm

Alternative, Supplemental Breast Imaging Methods Tested

HANOVER, N.H. – Dartmouth physicians and engineers are collaborating to test three new imaging techniques to find breast abnormalities, including cancer. Results from the first stage of their research, information about the electro-magnetic characteristics of healthy breast tissue, appears in the May 2004 issue of Radiology, the journal of the Radiological Society of North America.

The interdisciplinary team, which includes researchers from Dartmouth's Thayer School of Engineering and Dartmouth Medical School working with experts at the Norris Cotton Cancer Center and the Department of Radiology at Dartmouth-Hitchcock Medical Center (DHMC), is developing and testing imaging techniques to learn about breast tissue structure and behavior. The techniques are electrical impedance spectral imaging (EIS), microwave imaging spectroscopy (MIS), and near infrared (NIR) spectral imaging.

"This study offers the foundation for future research and clinical trials," says Steven Poplack, associate professor of radiology and OB/GYN at Dartmouth Medical School, doctor of diagnostic radiology and Co-Director for Breast Imaging/Mammography at DHMC, and the lead author of the paper. "We're establishing normal ranges for healthy breast tissue characteristics in order to more easily recognize the abnormalities."

The study of 23 healthy women offers baseline data from the three techniques. The methods are not invasive or particularly uncomfortable for participants, and they all provide detailed information about different properties of breast tissue.

* EIS: This painless test uses a very low voltage electrode system to examine how the breast tissue conducts and stores electricity. Living cell membranes carry an electric potential that affect the way a current flows, and different cancer cells have different electrical characteristics.

* MIS: This exam involves the propagation of very low levels (1000 times less than a cell phone) of microwave energy through breast tissue to measure electrical properties. This technique is particularly sensitive to water. Generally, tumors have been found to have more water and blood than regular tissue.

* NIR: Infrared light is sensitive to blood, so by sending infrared light through breast tissue with a fiber optic array, the researchers are able to locate and quantify regions of oxygenated and deoxygenated hemoglobin. This might help detect early tumor growth and characterize the stage of a tumor by learning about its vascular makeup.

[chubtoad]

http://www.scienceda...40503054534.htm

Researchers Confirm Genetic Link Between Hereditary Breast And Prostate Cancer

NEW YORK, May 1, 2004 – A new study shows that the risk for prostate cancer is significantly elevated in men who are part of families with a hereditary form of breast and ovarian cancer. Researchers at Memorial Sloan-Kettering Cancer Center have determined that men in families carrying BRCA genetic mutations have a three- to five-fold increased risk of prostate cancer.

"While the association between hereditary breast and prostate cancer has been suspected, this is the first study of its type to confirm the link," said Kenneth Offit, MD, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering and senior author of the study, which is published in the May 1 issue of Clinical Cancer Research.

Researchers obtained DNA specimens from 251 men of Eastern European (Ashkenazi) Jewish ancestry who had prostate cancer but were otherwise unselected on the basis of personal or family history. The blood samples were tested for mutations of the BRCA1 and BRCA2 genes and compared to specimens taken from 1,472 healthy men. Investigators pinpointed BRCA2 – not BRCA1 – as the common genetic link to prostate cancer.

The results show that the frequency of certain BRCA1 and BRCA2 mutations was 5.2 percent in the prostate cancer cases compared to 1.9 percent in the healthy volunteers. When stratified by gene, the risk for prostate cancer was 4.8 times higher in carriers of a specific BRCA2 mutation than in the healthy individuals tested.

"While the participants in the study were of Ashkenazi Jewish ancestry, the results may apply to all individuals with BRCA2 mutations," said Noah Kauff, MD, a gynecologist and geneticist at Memorial Sloan-Kettering and a co-author of the study.

The study authors point out that the age of onset of prostate cancer in men carrying these mutations was no different than in most men diagnosed with prostate cancer in the general population. "Since the age of onset for prostate cancer in men carrying the BRCA2 mutation does not appear to be earlier than in the general population, this would indicate that prostate cancer screening may begin at age 50, as is recommended in the general population, assuming the findings are confirmed in future studies" said Sherri Donat, MD, a urologic surgeon at Memorial Sloan-Kettering and co-author of the study.

The American Cancer Society recommends for men at average risk that prostate cancer screening with serum PSA testing and regular examinations be offered beginning at age 50.

[chubtoad]

http://www.cancerres...cergene_may1704

Scientists confirm new breast cancer gene

Release date: 17 May 2004
 
INHERITING the wrong version of a gene called CHEK2 doubles a woman's risk of developing breast cancer, Cancer Research UK scientists confirm in a major new international study published in the June edition of the American Journal of Human Genetics.

CHEK2 is the first 'low risk' gene to have been definitely established as a risk factor. It follows the identification in the mid-nineties of the high-risk genes, BRCA1 and BRCA2.

The possibility of offering genetic testing for this gene in women with a strong family history of breast cancer is now being researched.

The link between CHEK2 and breast cancer was first proposed in 2002, when a faulty version of the gene was found to be present in some cases with a strong family history of breast cancer. 'Strong family history' indicates at least two close family members have had the disease.

Today's research, coordinated and analysed by Cancer Research UK's Genetic Epidemiology Unit at the University of Cambridge, examined the genes of breast cancer patients and the wider population in the UK, Australia, Finland, Germany and the Netherlands.

The report confirms that the faulty version of the gene, called CHEK2*1100delC, was more common in women diagnosed with breast cancer than in healthy women. In total, they examined the CHEK2 genes of 10,860 women with breast cancer and 9,065 healthy women.

The 1100delC variant was found in 201 women with breast cancer (1.9%) and in 64 healthy individuals (0.7%). Scientists calculate from this that having the variant CHEK2 gene approximately doubles the risk of developing breast cancer, whether or not there is a history of breast cancer in the family.

Lead researcher Professor Doug Easton, of the Cancer Research UK Genetic Epidemiology Unit, says: "Women with a strong family history of breast cancer can already receive genetic tests for the BRCA genes. The next step will be to evaluate whether testing for CHEK2 is useful in the clinic. At the moment it is not clear in what contexts CHEK2 testing would be appropriate.

"As we identify more genes that impact on hereditary breast cancer, we move closer to a comprehensive genetic test to accurately assess the risk of inheriting the disease."

Women in the general population in the UK have a one in nine chance of developing breast cancer at some point in their lifetime. Carrying CHEK2*1100delC would increase this risk to about one in four. CHEK2 is the first confirmed 'low risk' gene. Scientists believe a number more exist, each pushing up the risk of breast cancer to a moderate degree.

The data suggest the increase in risk was greater for women diagnosed at a younger age. Hereditary factors are generally more important in cancers that occur in younger women.

Professor Easton adds: "This is perhaps the largest study of its kind. It is the most reliable method for calculating the impact of potential breast cancer genes, and is also being applied to other types of cancer."

Scientists believe the normal CHEK2 gene shuts down cells in a safe and controlled way upon detection of DNA damage. This prevents the cell from passing on faulty DNA, and allows time for repair mechanisms to be engaged. If a normal cell is like a car on the motorway, CHEK2 is responsible for spotting problems, pulling onto the hard shoulder and calling the AA.

CHEK2*1100delC is missing a vital piece – the brake pedal in the car – and is unable to initiate shutdown. Carrying this version means faults in other genes are more likely to evade the body's own repair processes and replicate themselves, potentially leading to a tumour.

Professor Robert Souhami, Director of Clinical and External Affairs at Cancer Research UK, says: "Identifying the first of a new set of breast cancer genes puts us in a much better position to tackle breast cancer, both through testing high-risk groups and eventually through new clinical strategies. "

[chubtoad]

http://newsroom.ucla...asp?RelNum=5201

Herceptin and Chemotherapy Combination Highly Active in the Treatment of Advanced Breast Cancer, Two UCLA Studies Find

Date: May 18, 2004
Contact: Kim Irwin ( kirwin@mednet.ucla.edu )
Phone: 310-206-2805

A pair of studies at UCLA's Jonsson Cancer Center that takes laboratory science to the patients' bedside found that combining the molecularly targeted therapy Herceptin with a specific chemotherapy combination resulted in significant tumor response rates and longer relapse-free periods in women with an aggressive form of advanced breast cancer.

The results of the studies, the first done on cell lines in the laboratory and the second translated into more than 120 patients in two Phase II clinical trials, appear May 18 in the peer‑reviewed Journal of the National Cancer Institute.

In an accompanying editorial, Dr. George W. Sledge Jr., co-director of the Breast Cancer Program at the Indiana University School of Medicine, called the studies "an impressive example of translational research at its best."

"Designing a sequential series of experiments, both laboratory and clinical, that lead intentionally to proof-of-concept adjuvant (Phase III) trials is all too rare," Sledge states in the editorial. "But, as (UCLA researchers) remind us, it is not impossible."

Jonsson Cancer Center researchers first tested drug combinations in the laboratory with the goal of translating their results into patients with HER2/neu amplification, a genetic alternation found in 20 percent to 25 percent of patients that leads to an aggressive form of breast cancer.

Lead by researchers Dr. Dennis Slamon and Dr. Mark Pegram, the laboratory studies analyzed Herceptin for interaction with nine chemotherapy drugs commonly used to treat breast cancer. Researchers found that the chemotherapy agents Taxotere, Navelbine, Cyclophosphamide and the platinum salts Cisplatin and Carboplatin increased the activity of Herceptin in lab models with HER2/neu amplification. In other words, Herceptin and the chemotherapy agents each made the other more effective, a synergistic effect. The laboratory studies pointed researchers to the optimum chemotherapy combination, which they then tested in the clinic.

In two Phase II clinical trials, Taxotere was given with Herceptin in combination with either Cisplatin or Carboplatin to women who tested positive for the HER2/neu alteration. Each study enrolled 62 women. Responses — shrinkage in tumor size — were observed in 79 percent of patients in one of the studies and in 58 percent of patients in the other. Additionally, the period before the cancer continued to grow again, called time to progression, was unusually long in the study subjects with this aggressive form of breast cancer.

"The median times to progression emerging from the trials are among the longest times reported to date for a patient population with HER2-amplified metastatic breast cancer," said Pegram, director of the Women's Cancer Program Area at UCLA's Jonsson Cancer Center and the lead author of the studies.

"Response rates were extraordinary," Pegram said, "superior to what was expected."

[chubtoad]

http://www.scienceda...40524060113.htm

Largest Study Of Its Kind Finds Male Breast Cancer On The Rise

HOUSTON - The rate of male breast cancer is on the rise and the disease in men is usually detected when the tumors are bigger, have spread and may be more aggressive, compared to diagnosis of the disease in women, concludes the largest study ever conducted of male breast cancer.

The findings, published today in the online edition CANCER and will appear in the July 1 print issue of the publication, suggest both that breast cancer in men may have some important biological differences from the female disease, and that men are seemingly less aware than they should be that they can develop breast cancer.

According to the study's lead investigator, Sharon H. Giordano, M.D., assistant professor in the Department of Breast Medical Oncology at The University of Texas M. D. Anderson Cancer Center, the incidence of the disease has increased significantly in the last 25 years, from .86 to 1.08 per 100,000 men.

"Male breast cancer is rare, accounting for less than one percent of all breast cancer, or about 1,600 new cases in the United States in 2004. While, it's not as high of an increase in cases as that in women, men should be alert to the possibility that the disease could affect them," says Giordano.

Because breast cancer in men is rare, little is known about how it differs from breast cancer in women and how it should be best treated. To assess dissimilarity, Giordano and her M. D. Anderson colleagues used information from a National Cancer Institute database called SEER (Surveillance, Epidemiology, and End Results), which is the authoritative source of information on cancer incidence and survival in the United States.

They analyzed SEER data from 1973 through 1998 on 2,524 cases of male breast cancer and 380,856 cases of female breast cancer. Compared to female patients, the investigators found that male patients were significantly older when diagnosed - 67 years versus 62 years of age. They were also more likely to have later stage disease and had more spread of the cancer to their lymph nodes.

"It's perhaps ironic that tumors in men are easier to feel than they are in women, yet the disease is being discovered at a later stage in men than in women," says Giordano.

One reason for such a late diagnosis may be that men assume they are experiencing a benign condition called gynecomastia, or atypical growth of breast tissue that affects about a third of males at some point in their lives, says Giordano. The condition, common in adolescent boys, can come and go over a man's lifetime and "men may think new growth of breast tissue is just another occurrence of this condition," she explains.

Furthermore, Giordano and the researchers found that the most common types of cancers in men were invasive ductal carcinoma, found in 93.4 percent of the men, and papillary carcinoma, which accounted for 2.6 percent of the cases.

Yet despite these differences, five-year, 10-year and median survival were not different between men and women, investigators say.

Also of interest to the researchers was the finding that male patients are more likely than female patients to have estrogen receptor-positive tumors.

"We are not sure why this is so, but it may indicate some important differences in tumor biology," she says. "In addition, this implies that use of tamoxifen in men may be as beneficial as it is to many women," says Giordano.

"Now that we have a clearer understanding of the biology of breast cancer in men, further research is needed to determine the optimal treatment for men," she says.

[chubtoad]

http://www.eurekaler...ct/medicine.php

Aspirin use associated with reduced risk of breast cancer

Women who report regular use of aspirin appear to have a reduced risk of breast cancer, according to a study in the May 26 issue of The Journal of the American Medical Association (JAMA).
While cancer epidemiology and prevention have traditionally focused on the identification and modification of lifestyle factors that may increase or decrease the risk of various cancers, much recent attention has been centered on chemoprevention, the use of chemical agents to prevent or inhibit the carcinogenic process, according to background information in the article. Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with a decrease in the risk of several cancers, including breast cancer. Given the importance of estrogen in the pathogenesis of breast cancer, the ability of aspirin and other NSAIDs to protect against breast cancer could vary according to hormone receptor status.

Mary Beth Terry, Ph.D., of Columbia University, New York, and colleagues conducted a study to determine the association between the frequency and duration of use of aspirin and other NSAIDs and breast cancer risk and whether any observed association is more pronounced for women with hormone receptor–positive breast cancers. The study, which included in-person interviews, was conducted during 1996-1997. There were 1,442 breast cancer cases and 1,420 controls.

The researchers found that ever use of aspirin or other NSAIDs at least once per week for 6 months or longer was reported in 301 cases (20.9 percent) and 345 controls (24.3 percent) with a 20 percent lower risk of breast cancer for ever use vs. nonusers. "The inverse association was most pronounced among frequent users [7 or more tablets per week, 28 percent lower risk]. The results for ibuprofen, which was used by fewer women on a regular basis, were generally weaker [22 percent lower risk for less than 3 times per week vs. 8 percent lower risk for 3 times or more per week]. Use of acetaminophen, an analgesic that does not inhibit prostaglandin synthesis, was not associated with a reduction in the incidence of breast cancer. The reduction in risk with aspirin use was seen among those with hormone receptor–positive tumors [26 percent lower risk] but not for women with hormone receptor–negative tumors," the authors write.

[Lazarus Long]

I was listening to this discussion just yesterday and I think we ought to open a thread on aspirin alone. It deserves much closer scrutiny because as an NSAID it is relatively unique in the anti-carcinogenic property it has. It appears related to COX-2 inhibitors and not all NSAID's act in this manner. Tylenol for example has little to no effect.

http://orthopedics.a...gs/a/nsaids.htm

http://www.jr2.ox.ac...ncer/CP082.html

There is a lot of focus now being brought to bear on the COX-2 Inhibitor and an aspirin a day appears to work remarkably well as a cancer preventative as well as being low cost. Also the dosage seems to be small and a baby aspirin is sufficient. 81 to 100 mg.

I find it ironic and kind of amusing for a folk remedy (Willow Bark) to have such potency.

[chubtoad]

http://www.eurekaler...ct/medicine.php

Gene expression ratio identifies risk of recurrence in breast cancer patients receiving tamoxifen
Research from MGH, Arcturus could indicate which patients need alternative treatment

A simple measurement of the expression levels of two genes in breast cancer tissue appears to identify tumors that are more likely to recur in women treated with tamoxifen for early-stage disease. Determining patients for whom tamoxifen treatment is likely to fail would allow earlier use of other therapies that could be more effective for those women.
Researchers from the Massachusetts General Hospital (MGH) Cancer Center and Arcturus Bioscience, Inc., describe their findings in a report to be published in the June issue of Cancer Cell. The paper is being released online today (www.cancercell.org) because related material is being presented at the June 5-8 American Society for Clinical Oncology meeting. The study was supported by grants from the Avon Foundation, the U.S. Department of Defense, and the National Cancer Institute.

Tamoxifen, which blocks the interaction between the hormone estrogen and its receptor protein, is used to treat breast cancers that express the estrogen receptor. However, only two thirds of these patients have a prolonged response to the drug. "Until now, there has been no way to predict which estrogen-receptor-positive patients will not respond to tamoxifen treatment," says Dennis Sgroi, MD, director of Breast Pathology at MGH who led the hospital's research team. "Identifying those for whom tamoxifen is likely to fail could allow physicians to choose other drugs, for instance the aromatase inhibitors that more completely block estrogen's action." Sgroi is an associate professor of Pathology at Harvard Medical School.

The hormone estrogen can stimulate both the normal growth of breast tissue and the uncontrolled growth of breast cancer. Cells from most breast tumors contain estrogen receptor molecules, indicating that the tumor's growth is likely to be sensitive to the hormone's action. Estrogen-blocking drugs have been used in recent years to prevent hormone-sensitive breast tumors from recurring after surgery and to treat metastasis. More than 500,000 U.S. women currently take tamoxifen, making it the most frequently used drug of this class.

[chubtoad]

http://www.aacr.org/2004pressc.asp

Albany High School Student Adds to Understanding of Breast Cancer Gene

A high school student from Albany, New York, has made a significant contribution toward understanding how mutations to a gene called BRCA-1 contributes to hereditary breast cancer.

Meaghan Figge, a sophomore at Albany Academy for Girls, published her results in the June issue of Cancer Epidemiology Biomarkers and Prevention, detailing the likely sites for BRCA-1 mutations leading to breast cancer. Figge is a student member of the American Association for Cancer Research, which publishes CEBP.

Figge pursued her research in memory of her grandmother, Helen Luciw, who died from breast cancer at age 64. Meaghan was in the fourth grade at the time, and in the years since, wondered whether screening methods other than the mammogram that detected her grandmother’s tumor could diagnose cancer at an earlier stage. Her curiosity led her to the literature biomedical research where she learned about BRCA-1, which under normal circumstances, acts to suppress tumors.

“I was curious about BRCA-1 gene,” Figge recalled. “On my own time, I read literature and did independent science research at my school to learn all I could about how this gene was related to breast cancer.”

Figge learned that normally, the BRCA-1 protein acts to suppress breast and ovarian tumors in women.

But when the genetic code for BRCA-1 is errantly altered, the gene may lose its ability to suppress tumors.

“Some women inherit abnormal forms of BRCA-1 and are at an increased risk of developing breast or ovarian cancer,” she said.

The abnormal forms of the gene result in a protein form of BRCA-1 that contains amino acid substitutions that differ from the normal gene. Changes in the amino acid composition of the BRCA-1 protein stem from alterations in the genetic sequence of nucleotides that make up the coding for the gene, which is part of each woman’s unique DNA makeup.

Although only five to 10 percent of all breast cancer cases are linked to inherited genes, women with abnormal BRCA-1 genes have as much as almost 90 percent more risk of developing breast cancer during their lifetime. Half of all hereditary cases of breast cancer are associated with abnormal BRCA-1 genes.

The BRCA-1 gene is not unique to humans. The scientific literature already documents that the gene sequence for BRCA-1 remains similar across a number of mammalian species. Humans and dogs share about 96 percent of the same coding sequence within the gene, while humans and rodents such as mice and rats have less consistency in gene sequence—about 65 percent of the genetic coding is similar.

Figge considered whether the amino acids that were encoded by the conserved portion of the BRCA-1 gene found in the various species served as potential mutations sites leading to loss of function of the gene and increased risk for breast cancer for the person carrying the gene.

Under the guidance of her mentor, chemistry teacher, and manuscript co-author, Lynda Blankenship, Figge examined 246 different BRCA-1 sequence mutations found in humans considered at high risk for breast or ovarian cancer. The genetic information for those people was provided from many different clinical settings and compiled in the NIH Breast Cancer Information Database—a repository of genetic sequences for a multitude of genes found in breast cancer patients.

Figge’s analysis of the NIH data revealed that among the known BRCA-1 mutations, sites within the genetic coding that were likely targets of mutation were the same sites conserved among humans, dogs, rats and mice. Furthermore, Figge documented that among the conserved amino acids that make up the BRCA-1 protein in the four species, the amino acids that were most likely to be mutated were those that are hydrophobic. Mutated BRCA-1 proteins that exchange hydrophobic amino acid residues for more water-loving types of amino acids may undergo structural changes that lead to loss of function. The mutations found in the abnormal BRCA-1 versions may lead to proteins that are bent out of shape and unable to perform as tumor suppressers.

[chubtoad]

http://www.eurekaler...ct/medicine.php

Tamoxifen stimulates breast cancer growth following alteration of estrogen receptor

Scientists have discovered that resistance to tamoxifen treatment can be mediated by a modification of the estrogen receptor. These results enhance the understanding of what underlies tamoxifen resistance in breast cancer and may eventually allow for earlier identification of resistant tumors, providing critical time to choose an alternative therapeutic strategy that is more likely to be effective.
Because nearly three-quarters of all breast cancers are stimulated by estrogen acting at functional estrogen receptors (ER+), they are most often treated with anti-estrogen compounds that inactivate the estrogen receptor. The most common of these is the drug tamoxifen. However, only about half of ER+ breast cancers successfully respond to treatment with tamoxifen, while the other half are resistant. When tamoxifen is used in advanced disease, resistance will eventually arise in all tumors, even if they were initially sensitive. It has been reported that tamoxifen-resistant breast tumors sometimes stop growing when tamoxifen is withdrawn. Dr. Rob Michalides and colleagues from the Department of Tumor Biology at The Netherlands Cancer Institute found that activation of the enzyme protein kinase A (PKA) induced tamoxifen resistance in breast cancer cells through a unique mechanism. PKA modified the estrogen receptor in such a way that although tamoxifen could still bind, it could no longer convert the receptor to an inactive form. Instead, it acted as an estrogen receptor activator and encouraged tamoxifen-resistant cancer cell growth. Using a genetic screening technique, the researchers showed that this mechanism was also operational in patients.

The findings indicate that PKA may be a critical determinant of how ER+ breast cancers respond to tamoxifen. "This is highly relevant for breast cancer patients, since tamoxifen might induce the opposite effect when PKA is activated, stimulating ER+ tumor growth instead of inhibiting it. Such patients should be identified and treated with other hormonal agents, such as aromatase inhibitors or with a pure anti-estrogen such as fulvestrant," explains Dr. Michalides.

[chubtoad]

http://www.eurekaler...ct/medicine.php

MRI better than mammography for detecting number & size of breast cancer tumors

Researchers from the Abramson Cancer Center at the University of Pennsylvania presented -- at the ASCO meeting in New Orleans -- comprehensive study results which show that MRI is significantly better than mammography for detecting the presence & extent of disease in patients with breast cancer. The research has significant implications for women considering surgical options -- other than a full mastectomy -- to remove their breast cancer. Abramson researchers led the 1st international, multi-site group of researchers to study the subject -- the International Breast MRI Consortium.
NIH/National Cancer Institute