Tuesday, March 19, 2013

Less frequent mammograms don't increase risks after age 50 : study

By Julie Steenhuysen

CHICAGO (Reuters) - In the latest installment in the mammogram debate, a new study finds that getting a mammogram every other year instead of annually did not increase the risk of advanced breast cancer in women aged 50 to 74, even in women who use hormone therapy or have dense breasts, factors that increase a woman's cancer risk.

The findings, released on Monday by researchers at the University California, San Francisco, support the conclusions of the U.S. Preventive Services Task Force, an influential government panel of health advisers, which in 2009 issued guidelines that said women should have mammograms every other year starting at age 50 rather than annual tests starting at age 40.

The controversial recommendations to reduce the frequency and delay the start of mammogram screening were based on studies suggesting the benefits of detecting cancers earlier did not outweigh the risk of false positive results, which needlessly expose women to the anguish of a breast cancer diagnosis and the ordeal of treatment.

The matter, however, is not settled. The American Cancer Society still recommends women be screened for breast cancer every year they are in good health starting at age 40, but the group is closely watching studies such as this.

"I don't think any one study ought to change everything," Dr. Otis Brawley, chief medical officer of the American Cancer Society, said in a telephone interview. But he added, "This is one of several studies that are all pointing in the same direction over the last several years."

Brawley said he did not expect screening recommendations from professional organizations to change in the next year, but he does see doctors moving toward a more personalized approach over the next five years. There may be some women who need to be screened every six months and others every two years depending on their breast density, family history and genetic testing.

In the latest study, Dr. Karla Kerlikowske of the University of California, San Francisco, and colleagues wanted to see whether risk factors beyond a woman's age play a role in the decision of when to start mammogram screening.

In addition to age, the team considered whether women had dense breast tissue - which has a higher ratio of connective tissue to fat - or took combination estrogen and progesterone hormone therapy for more than five years, both of which can increase the risk of breast cancer.

"If you have these risk factors, would it help if you got screened annually vs. every two years?" said Kerlikowske, whose study was published online in JAMA Internal Medicine.

To study this, the team analyzed data from 11,474 women with breast cancer and 922,624 without breast cancer gathered from 1994 to 2008. Even after looking at these other factors, the team found no increased risk of advanced cancer in women 50 to 74 who got a mammogram every other year instead of every year.

"It didn't matter whether you screened that group every year or every two years, the risk of advanced disease or having a worse tumor was no different," Kerlikowske said.

PSYCHOLOGICAL EFFECTS

More frequent screening in these women did result in more false-positive results. Women aged 50 to 74 who had annual mammograms had a 50 percent risk of having a false-positive result over a 10-year period, but a 31 percent risk when they were screened every other year.

Studies suggest a false positive can have lasting psychological effects. A March study in the Annals of Family Medicine said, "Three years after a false-positive ?nding, women experience psychosocial consequences that range between those experienced by women with a normal mammogram and those with a diagnosis of breast cancer."

Breast density was a factor in younger women, however. When the team looked at screening frequency in women 40 to 49, they found those with extremely dense breasts who were screened every other year had a higher risk of having a more advanced cancer than those who got screened every year. Younger women also were far more likely to have false-positive results and undergo unnecessary procedures.

Without getting a mammogram in their 40s, Kerlikowske said, "women aren't going to know if they have extremely dense breasts."

Among women in their 40s, about 12 percent to 15 percent have extremely dense breast tissue. For these women, Kerlikowske said she recommends that they get a mammogram if they have other risk factors that might put her at risk of breast cancer, including having a first-degree relative that a common term, or just "close relative"? such as a mother or a sister with breast cancer.

"Once we see their breast density is high, we will offer annual mammography," she said.

The American College of Radiology and the Society of Breast Imaging, groups that represent radiologists, said the study's methodology was flawed because it used early and late breast cancers to determine the outcomes of breast screening rather than more refined measures of tumor size, nodal status and cancer stage, which could determine whether screening detected cancers at an earlier stage.

It also faulted the study for not being a closely controlled, randomized clinical trial. The study used data from the Breast Cancer Surveillance Consortium, a national mammography screening database that gathers information from community mammography clinics on millions of women.

"We're never going to have a randomized study. This is the best in terms of the type of study anyone can actually hope for," said Brawley, whose group monitors scores of breast studies from around the world each year. He said such a study would take decades and would be prohibitively expensive.

Catching cancers earlier does not always translate into lives saved, according to a November study published in the New England Journal of Medicine by Dr. Gilbert Welch of the Dartmouth Institute for Health Policy & Clinical Practice in New Hampshire.

That study suggested that as many as a third of cancers detected through routine mammograms may not be life-threatening, contradicting the deeply ingrained belief that cancer screening is always good.

Kerlikowske said the strength of her study is that it allows researchers to consider other risk factors, such as breast density, allowing doctors to offer women personalized choices about when to start breast cancer screening.

"We're trying to move it away from this idea that it all should be based on age. There should be some thoughtfulness to it," she said.

(Reporting by Julie Steenhuysen; Additional reporting by Bill Berkrot; Editing by Jilian Mincer and Douglas Royalty)

Source: http://news.yahoo.com/less-frequent-mammograms-dont-increase-risks-age-50-000253868.html

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Wednesday, March 6, 2013

UT Southwestern scientists make mouse model of human cancer, demonstrate cure

UT Southwestern scientists make mouse model of human cancer, demonstrate cure [ Back to EurekAlert! ] Public release date: 5-Mar-2013
[ | E-mail | Share Share ]

Contact: Deborah Wormser
deborah.wormser@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

DALLAS March 5, 2013 UT Southwestern Medical Center scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer.

"To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor," said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study published in Cell and online. The study's first author is Dr. Wei Mo, a postdoctoral researcher in the department.

"We showed that blocking the activity of a receptor molecule named CXCR4 in these tumors through genetic manipulation or by chemical blockade inhibited tumor development. Together, these data reveal a potential target for therapy of these uncommon but currently untreatable malignant peripheral nerve sheath tumors (MPNSTs)," Dr. Parada added.

The study is a collaboration between Dr. Parada's laboratory and that of Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology. Dr. Le also is co-director of the adult Comprehensive Neurofibromatosis Clinic at UT Southwestern, the first such clinic in North Texas, which is part of the Simmons Comprehensive Cancer Center. The researchers noted that co-authors at The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, greatly accelerated the research effort.

MPNSTs are rare but highly aggressive tumors that are resistant to therapy and are typically fatal. The malignancies can occur sporadically or in a subset of patients with a condition called neurofibromatosis 1 (NF1) one of the most commonly inherited disorders of the nervous system, which affects an estimated 1 in 3,500 people.

The severity of NF1 can vary widely, even among family members, from mild dermatological symptoms to benign tumors that wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form, Dr. Le said. In addition, individuals with an improperly-functioning NF1 gene have an increased risk of developing cancerous tumors such as MPNSTs, he said.

The researchers generated a mouse model that spontaneously develops MPNSTs and compared gene expression activity in cancerous tumors and in the precursor cells that give rise to the tumors, which are the kind of cells in which MPNSTs develop.

They found that a protein (CXCR4), which is essential for tumor growth, is more abundant in cancerous cells than in precursor cells. In addition, they found that a molecule produced by the cancer cells themselves (CXCL12) works with CXCR4 to further the growth of cancer by stimulating the expression of the cyclin D1 protein, which promotes cell division via a signaling pathway outlined in the study.

When they examined human MPNSTs, the scientists found increased expression of CXCR4 accompanied by activity in the same pathway as the one identified in the mice, the researchers said.

Next, they blocked the activity of CXCR4 in the MPNST mice using either genetic manipulation or an FDA-approved antagonist drug for CXCR4 called AMD3100. Both strategies inhibited cancer development in mice whose tumors expressed increased levels of CXCR4, and were less effective in tumors without increased CXCR4 expression. They identified the same situation in the human cancer cells, the researchers report.

"We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today," said Dr. Le, who added that the researchers are currently planning human trials.

###

Funding was provided by the National Cancer Institute, the Department of Defense, the National Institutes of Health, the Burroughs Wellcome Fund, and the American Cancer Society.

UT Southwestern co-authors include: Dr. Jian Chen, a former postdoctoral researcher in developmental biology now a senior scientist at OriGene Technologies in Wuxi, China; Amish Patel, a graduate student of cancer biology; Dr. Liang Zhang, a postdoctoral researcher of cell biology; Vincent Chau, a medical scientist training program student of developmental biology; Yanjiao Li, a research associate of developmental biology; Dr. Woosung Cho, a postdoctoral researcher of developmental biology; Dr. Sang Kyun Lim, an instructor of developmental biology; Jing Xu, a senior research associate; and Dr. Rene McKay, an assistant professor of developmental biology.

Visit UTSW Medicine at http://www.utswmedicine.org/cancer to learn more about UTSW's clinical services for cancer. Information for the Comprehensive Neurofibromatosis Clinic is located at http://www.utswmedicine.org/conditions-specialties/cancer/programs/neurofibromatosis/.

About UT Southwestern Medical Center

UT Southwestern, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 100,000 hospitalized patients and oversee more than 2.1 million outpatient visits a year.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at http://www.utsouthwestern.edu/receivenews


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UT Southwestern scientists make mouse model of human cancer, demonstrate cure [ Back to EurekAlert! ] Public release date: 5-Mar-2013
[ | E-mail | Share Share ]

Contact: Deborah Wormser
deborah.wormser@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center

DALLAS March 5, 2013 UT Southwestern Medical Center scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer.

"To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor," said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study published in Cell and online. The study's first author is Dr. Wei Mo, a postdoctoral researcher in the department.

"We showed that blocking the activity of a receptor molecule named CXCR4 in these tumors through genetic manipulation or by chemical blockade inhibited tumor development. Together, these data reveal a potential target for therapy of these uncommon but currently untreatable malignant peripheral nerve sheath tumors (MPNSTs)," Dr. Parada added.

The study is a collaboration between Dr. Parada's laboratory and that of Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology. Dr. Le also is co-director of the adult Comprehensive Neurofibromatosis Clinic at UT Southwestern, the first such clinic in North Texas, which is part of the Simmons Comprehensive Cancer Center. The researchers noted that co-authors at The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, greatly accelerated the research effort.

MPNSTs are rare but highly aggressive tumors that are resistant to therapy and are typically fatal. The malignancies can occur sporadically or in a subset of patients with a condition called neurofibromatosis 1 (NF1) one of the most commonly inherited disorders of the nervous system, which affects an estimated 1 in 3,500 people.

The severity of NF1 can vary widely, even among family members, from mild dermatological symptoms to benign tumors that wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form, Dr. Le said. In addition, individuals with an improperly-functioning NF1 gene have an increased risk of developing cancerous tumors such as MPNSTs, he said.

The researchers generated a mouse model that spontaneously develops MPNSTs and compared gene expression activity in cancerous tumors and in the precursor cells that give rise to the tumors, which are the kind of cells in which MPNSTs develop.

They found that a protein (CXCR4), which is essential for tumor growth, is more abundant in cancerous cells than in precursor cells. In addition, they found that a molecule produced by the cancer cells themselves (CXCL12) works with CXCR4 to further the growth of cancer by stimulating the expression of the cyclin D1 protein, which promotes cell division via a signaling pathway outlined in the study.

When they examined human MPNSTs, the scientists found increased expression of CXCR4 accompanied by activity in the same pathway as the one identified in the mice, the researchers said.

Next, they blocked the activity of CXCR4 in the MPNST mice using either genetic manipulation or an FDA-approved antagonist drug for CXCR4 called AMD3100. Both strategies inhibited cancer development in mice whose tumors expressed increased levels of CXCR4, and were less effective in tumors without increased CXCR4 expression. They identified the same situation in the human cancer cells, the researchers report.

"We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today," said Dr. Le, who added that the researchers are currently planning human trials.

###

Funding was provided by the National Cancer Institute, the Department of Defense, the National Institutes of Health, the Burroughs Wellcome Fund, and the American Cancer Society.

UT Southwestern co-authors include: Dr. Jian Chen, a former postdoctoral researcher in developmental biology now a senior scientist at OriGene Technologies in Wuxi, China; Amish Patel, a graduate student of cancer biology; Dr. Liang Zhang, a postdoctoral researcher of cell biology; Vincent Chau, a medical scientist training program student of developmental biology; Yanjiao Li, a research associate of developmental biology; Dr. Woosung Cho, a postdoctoral researcher of developmental biology; Dr. Sang Kyun Lim, an instructor of developmental biology; Jing Xu, a senior research associate; and Dr. Rene McKay, an assistant professor of developmental biology.

Visit UTSW Medicine at http://www.utswmedicine.org/cancer to learn more about UTSW's clinical services for cancer. Information for the Comprehensive Neurofibromatosis Clinic is located at http://www.utswmedicine.org/conditions-specialties/cancer/programs/neurofibromatosis/.

About UT Southwestern Medical Center

UT Southwestern, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 100,000 hospitalized patients and oversee more than 2.1 million outpatient visits a year.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at http://www.utsouthwestern.edu/receivenews


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


Source: http://www.eurekalert.org/pub_releases/2013-03/usmc-uss030513.php

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