COX 2 Expression Is Marker For Cancer Development In Some Benign Breast Biopsies
It’s a good news, bad news situation. Some women who have a breast biopsy are told that while they don’t have cancer, they do have atypical hyperplasia — cells that aren’t quite normal and might become cancerous someday. This happens to one-fourth of women undergoing chest biopsies but no one knows which individuals are at risk.
In their quest to discover who is at risk, researchers at Mayo Clinic (http://mayoresearch.mayo.edu/mayo/careful search/womens_cancer/breast_excellence.cfm) are building a biopsy profile to try to predict cancer outcome, and in the March 11 online edition of the Journal of the National Cancer Institute (http://jnci.oxfordjournals.org/rss/recent.xml), they report discovery a new variable to add to this contour.
The research team discovered that women whose atypia tissue expressed COX 2 enzymes were more likely to develop breast cancer subsequently, and that the more the enzyme expressed, the higher the put to hazard.
Specifically, 20 years after a biopsy in which atypia was lay the foundation of, 31 percent of women with high levels of COX-2 in their atypia sample had developed breast cancer, versus 14 percent of those with no COX-2 expression. For those with moderate levels of COX-2, 24 percent had developed breast cancer.
“Based on these findings, COX-2 expression in atypia may be a biomarker of risk of progression to breast cancer,” says the study’s senior investigator, Mayo Clinic oncologist Lynn Hartmann, M.D (http://mayoresearch.mayo.edu/mayo/research/staff/hartmann_lc.cfm). “COX-2 is a relevant candidate because it drives a number of malignant features and has been shown to be important in breast cancer.
“either year in the United States, about 1 million women have a benign breast biopsy; and some of them receive the worrisome news that they have atypical hyperplasia,” Dr. Hartmann says. If other studies validate these findings, she notes that one strategy to help manage patients may be to use a COX-2 inhibiting agent, such as celecoxib or rofecoxib, to prevent breast cancer from developing. “This study raises the possibility of targeting COX-2 in selected women to reduce their risk of breast cancer,” she says.
In the biopsy profile thus far, the Mayo risk model includes age, the number of regions of atypical cells in the biopsy, COX-2 expression and the status of the normal lobules in the breast.
“Our goal is to individualize risk for breast cancer so that we can provide effective care and risk reduction for each of our patients,” says Dr. Hartmann.
Cyxlooxygenase (COX) enzymes produce prostaglandin compounds responsible with regard to pain and inflammation, and nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to reduce expression of COX enzymes, although some NSAID use has been associated with side effects (most notably feasible kidney failure). COX-2 is a form of COX that is not usually found in normal tissues but which has been associated with several cancers, including ductal carcinoma in situ and invasive breast cancers.
In this study, researchers examined breast biopsy samples that contained atypia for COX-2 expression which has never been done before.
Investigators looked at 235 women who had a breast biopsy following a mammogram at Mayo Clinic from 1967 through 1991, and who were diagnosed with the atypical hyperplasia cell growth disarray.
During an average follow-up period of 15 years, 41 (17 percent) of the women developed breast cancer. The average time for that breast cancer to be diagnosed was 11.4 years.
The researchers examined the biopsies for the level of COX-2 expression and notwithstanding other variables, such as the number of areas (or foci) within the biopsy that contained atypical growth. They found that moderate expression was identified in 71 (30 percent) of the samples and that 34 (14 percent) of the biopsies exhibited strong expression of the enzyme.
The researchers calculated that, among the women in the study group, the absolute risk of developing bosom cancer 15 years after a diagnosis of atypical hyperplasia was 13 percent in biopsies with little or no COX-2 expression, 19 percent with moderate COX-2 expression, and 25 percent with strong COX-2 look. In women who had been followed for 20 years or more, the combination was more definitive: stratification of risk was 14 percent, 24 percent, and 31 percent, respectively. (Because the participants had atypical hyperplasia, they were all at increased baseline risk of developing breast cancer.)
The finding that risk of later breast cancer was associated with increasing levels of COX-2 expression was of borderline statistical significance (p=.07), likely due to the small sample size Dr. Hartmann says. “But higher expression levels were tightly linked to an increased number of abnormal foci in the biopsy, which we had earlier found to be a strong risk factor for breast cancer.”
The researchers also assessed the connected with risk of developing breast cancer, based on COX-2 expression in atypical hyperplasia, compared to a “control” number of people of unaffected women, and found that little COX-2 expression was associated with 2.6 times the risk, moderate COX-2 expression increased risk by 3.5 times, and a strong expression of COX-2 elevated risk by more than 5.6 times, compared to women in the catholic population.
“COX-2 appears to be a biomarker that more distant stratifies breast cancer risk among women with atypia and may be a relevant target for chemoprevention strategies,” says Dr. Hartmann.
Other Mayo Clinic researchers included V. Shane Pankratz, Ph.D.; Marta Santisteban, M.D., Ph.D.; Carol Reynolds, M.D.; Robert Vierkant; Wilma Lingle, Ph.D.; and Marlene Frost, Ph.D. Additional contributors included Daniel Visscher, M.D., from the University of Michigan, Ann Arbor and Ari Ristimaki, M.D., from the University of Helsinki, Finland.
Funding for the study was provided by the U.S. Department of Defense, and grants from Martha and H. Bruce Atwater Jr. and the Regis Foundation for Breast Cancer Research.
Mayo Clinic
200 First St. SW
Rochester, MN 55902
United States
http://www.mayoclinic.com
Urban Planning Linked To Rising Obesity Rates
You may want to buy healthy food for your family, but if the good grocery stores are far away and pricey and the fast-food outlets are cheap and plentiful, it may be harder to make the healthy choice. Research led by the University of Alberta and funded by the Canadian Institute for Health Information confirms there are links between our urban surroundings and how likable we are to struggle with obesity.
The startling rise in obesity rates in North America over the after two decades has led to calls for more effective approaches to help people achieve healthy weights. The State of the Evidence Review on Urban Health and Healthy Weights, released to the persons this week, synthesizes the tools and materials of hundreds of population health studies published over the years and shines a spotlight on aspects of our urban environments that can either inhibit or promote our ability to maintain a healthy weight.
“Two key areas we looked at were economic environments and built environments—meaning the ways in that the neighbourhoods and the cities in which we live are planned and developed,” said Kim Raine, director of the University of Alberta’s Centre notwithstanding Health Promotion Studies and lead author of the report.
“When we reviewed the evidence we found, for example, that lower-income neighbourhoods were more likely to have greater access to sources of high-calorie foods, such during the time that fast-food outlets, and lower access to supermarkets or other stores stocking healthy foods,” explained Raine. The report also found that a lower socio-economic status—that involves education level, income and employment—was often associated with increased obesity among both adults and children. “Lower personal income affects the affordability of food,” Raine said, “and that has been shown to have the most consistent influence on what people eat.”
The walkability of neighbourhoods and increase to recreational facilities in and around neighbourhoods may also assist in promoting healthy weights, according to the report. “Some hallmarks of walkability are increased residential density, mixed-use zoning and street connectivity,” said co-author John Spence from the U of A’s Faculty of Physical Education and Recreation. “Conversely, factors such as urban sprawl, low intersection density, low residential closeness and low land-use mix tend to also to favour sedentary behaviour and lower physical activity levels and raise fatness.”
The report also ground that individuals living in middle-income to high-income neighbourhoods were more likely to be physically active than their counterparts in lower-income neighbourhoods.
Raine, Spence and their fellow researchers conclude that interventions aimed at improving the income and educational status of individuals and families within urban environments may help address these disparities in obesity. “And improving access to healthy foods and recreation opportunities in lower-income neighbourhoods can too help to create a ‘healthy gravity’-friendly environment,” Spence reported.
No comments