WASHINGTON – A new analysis suggests the benefits of mammography screening every other year outweigh the potential harms for women aged 40 to 49 who are at an increased risk of developing breast cancer -- a finding that could affect one out of every five American women. The researchers also found greater harms from screening done with digital mammography compared to film mammography. These findings, with contributions from three national research groups, are published in the May 1 issue of Annals of Internal Medicine.
"Our research suggests the benefit-harm balance is tipped in favor of every-other-year screening for women in their 40s who are at about twice the average risk of developing breast cancer," says the study's senior author Jeanne Mandelblatt, M.D., M.P.H., associate director for population sciences at Georgetown Lombardi Comprehensive Cancer Center. "The study also determined that the balance of benefits and potential harms in this same group is not favorable when increasing the frequency of mammography screening to once a year."
Conditions that confer a two-fold increase in risk include having extremely dense breasts (13 percent of the population aged 40 to 49) or having a first-degree relative with breast cancer (9 percent of the population aged 40 to 49). A review of factors that increase breast cancer risk levels is also published in this issue of Annals of Internal Medicine (Nelson, et. al.)
The researchers characterized benefits of screening as life-years gained and breast cancer deaths averted. Harms are defined as false-positive mammography examinations that sometimes lead to additional procedures, and pain and anxiety.
Mandelblatt says putting these results into practice will not be straightforward. "For example, the need to have a mammogram to determine breast density is an important point to consider in regards to implementing risk-based guidelines based on breast density." Mandelblatt says some groups might see this as a reason to recommend a baseline mammography.
In 2009, the U.S. Preventive Services Task Force (USPSTF) recommended mammography screening every other year for women aged 50 to 74 who have an average risk of developing the disease. The USPSTF concluded that for average risk women aged 40 to 49 years, biennial screening mammography offered a small benefit but considerable harms. Its findings were based in part on earlier research conducted by Mandelblatt and her colleagues.
This new study also finds small differences in benefits between film and digital mammography screening. However, digital mammography screening did result in substantially more false-positive results than film, and thus greater harm. The researchers say women would need to have at least a four-fold increase in risk of developing breast cancer to start screening at age 40 using digital mammography and still have the same balance of benefits and harms as average risk women aged 50 to 74, Mandelblatt explains.
Mandelblatt emphasizes that their research findings are based on models of the U.S. population and don't constitute a recommendation or advice for individual women, but rather provide new information for groups who make breast cancer screening guidelines.
"These results are not intended to guide clinical care, but to provide evidence to groups striving to individualize screening guidelines based on risk factors," she explains. "Ultimately, though, the decision of when to start screening and how often, and whether to have digital or film mammography should be left to women and their health care providers."
The new research resulted from the collaboration of and data from three national research groups— the Breast Cancer Surveillance Consortium (BCSC), Cancer Intervention and Surveillance Modeling Network (CISNET) and the Oregon Evidence-based Practice Center.
Mandelblatt is an investigator with CISNET, which, for this study, utilized four well-established models from four international, independent research groups. The basic data used for the modeling were the same as those on which the USPSTF based their 2009 screening recommendations, but additional data regarding thresholds of risk was added for this new research. Cost was not a factor. BCSC, a research network of mammography registries in the United States, provided collaboration and some of the new data. As of 2011, the BCSC's database contains information on over 9.5 million mammograms, 114,000 breast cancer cases, and over 2.3 million women.
This study used comparative modeling. Separate modeling efforts often yield disparate results that are difficult to reconcile. A comparative modeling approach explores differences between models in a systematic way and results are compared across models. The models simulated life histories for populations of women estimating breast cancer incidence and deaths if they didn't receive screening and treatment. Then the models overlaid screening use and improvements in survival associated with treatment advances. Data interpretation was provided by the Oregon Evidence-based Practice Center. The researchers were able to establish a representation of the influence that breast cancer screening has on the simulated life histories based on risk levels.
Mandelblatt concludes, "Reducing the false-positive rate is crucial to improving the balance of benefits and harms for screening regimens for women of all ages."
The paper's lead author is Nicolien T. van Ravesteyn, M.Sc. of Erasmus MC in Rotterdam, The Netherlands. In additional to van Ravesteyn and Mandelblatt, authors include Diana L. Miglioretti, PhD; Natasha K. Stout, PhD; Sandra J. Lee, DSc; Clyde B. Schechter, MD, MA; Diana S.M. Buist, PhD; Hui Huang, MS, Eveline A.M. Heijnsdijk, PhD; Amy Trentham-Dietz, PhD; Oguzhan Alagoz, PhD; Aimee M. Near, MPH; Karla Kerlikowske, MD; Heidi D. Nelson, MD, MPH; and Harry J. de Koning, MD, PhD. (See manuscript for affiliation information.)
This research was supported by the National Cancer Institute (grant numbers U01CA086076-10S1, U01CA88283, U01CA152958, and KO5CA96940.) Data collection for this work was supported by the Breast Cancer Surveillance Consortium funded by a National Cancer Institute cooperative agreement (grant numbers U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040.)
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar 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. Georgetown Lombardi is one of only 40 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 http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health. In fiscal year 2010-11, GUMC accounted for 85 percent of the university's sponsored research funding.
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