PERSONALIZED MAMMOGRAPHY

July 5, 2011 — Current mammography guidelines offer recommendations on the basis of age alone, but a new study offers a different perspective. Instead of putting all women into a one-size-fits-all model, mammograms should be personalized on the basis of other factors, including age, breast density, family history of breast cancer, and a woman's values and preferences.
The study, published in the July 5 issue of the Annals of Internal Medicine, challenges the current guidelines from groups such as the American Cancer Society and the US Preventive Services Task Force, which make recommendations on the basis of age alone.
"Most guidelines use age as the determining factor for when and how often a woman should get a mammogram," said senior author Steven Cummings, MD, from the San Francisco Coordinating Center at the California Pacific Medical Center Research Institute.
"What our study shows is that other factors, particularly breast density, are just as important, if not more so, in helping a woman decide what is most appropriate for her," Dr. Cummings said in a statement.
Screening Based on Risk Factors
The authors conclude that women can choose to undergo mammography when they reach 40 years of age; those with low or average breast density and no other risk factors can choose to repeat screening at 50 years of age. Periodic screening can begin at that point.
They also conclude that, contrary to current guidelines, those between 50 and 79 years who have low breast density and no other breast cancer risk factors can consider getting screened less frequently than every 2 years.
For women between 40 and 49 years who have relatively high breast density or additional risk factors for breast cancer, undergoing biennial mammography is cost effective. Other factors, such as the potential emotional effect of mammography, should be taken into account when deciding when to begin a screening program and the appropriate time interval.
Impact on an Individual Level
First author John T. Schousboe, MD, PhD, from the Park Nicollet Institute and the University of Minnesota in Minneapolis, noted that their conclusions might be considered somewhat controversial because they differ from current mammography guidelines.
"I hope everyone looks...critically at the evidence we put into our model," he told Medscape Medical News.
Data from the Breast Cancer Surveillance Consortium, which has a database that contains information on 8,374,024 screening mammographic examinations, 86,700 breast cancer cases, and more than 2,300,000 women, did not show any difference between annual and biennial screening. "The premise for screening is to catch cancer early, so that it has more of a chance of being successfully treated," said Dr. Schousboe. "But annual screening was not better at detecting local cancers than screening every 2 years."
There was a big difference between women who had undergone no screening and those screened every 3 years, he added. With biennial screening, there was additional improvement in finding local cancers; with annual screening, there was no real improvement.
"There is not much gain for the increased cost, and that is what really drives what we found," said Dr. Schousboe.
Although their results might not change current guidelines, he feels that it could have some impact on a more individual level. "This may play out between individual doctors and patients," he noted. "If there is a low-risk patient, for example, who doesn't want to get a mammogram every year, then these data can help support that decision. [However], if there is a woman who gets tremendous reassurance from getting an annual mammogram, then by all means she should continue to do so."
Provocative But Needs Further Research
That breast density can be used to determine optimal screening strategies is a provocative result, write the authors of an accompanying editorial — Jeanne S. Mandelblatt, MD, MPH, from the Lombardi Comprehensive Cancer Center in Washington, DC; Natasha Stout, PhD, from Harvard Medical School and Harvard Pilgrim Health Care Institute in Boston, Massachusetts; and Amy Trentham-Dietz, PhD, from the University of Wisconsin Carbone Cancer Center in Madison.
"It suggests the presence of a biological mechanism that could be exploited to develop biomarkers, monitor risk, and screen for breast cancer on the basis of risk," they write in an accompanying editorial.
That said, the editorialist point out that as exciting as these advances in personalized risk-based screening appear to be, a number of obstacles remain. One is that the strategy evaluated in this study is dependent on women getting a baseline mammography at 40 years of age to determine density, followed by a discussion with the clinician to determine subsequent screening schedules. "This public health approach may be difficult to communicate, although the American Cancer Society promoted a similar approach in the past (for different reasons) with some success," the authors write.
Another concern is that the rates of a positive family history or previous breast biopsy are low, and 50% or more of the women 40 to 49 years of age fall into the categories of density found to be cost effective in this study. Thus, a number of women would be left without any guidance on when to begin screening, based on these risk factors alone.
A third obstacle, say the editorialists, is the premise that low-risk women can wait until 50 years of age to begin regular screening, and then even be screened less frequently than every 2 years. Although it would be cost effective, this approach might be difficult to communicate to women and would probably meet resistance.
"Although risk-based approaches show promise, further research is needed to overcome gaps in our knowledge of the underlying relationships between risk factors and the biology of breast cancer and to surmount the practical communication issues involved in implementing appropriate healthcare utilization based on personalized risk," they conclude.
Modeling Details
Dr. Schousboe and colleagues developed a model to compare the lifetime costs and health benefits for women who underwent mammograms every year, every 2 years, every 3 to 4 years, or who never underwent a mammogram. The cohort consisted of women in the United States 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years of age who had a baseline mammogram at age 40 and a breast density category of 1 to 4 (Breast Imaging Reporting and Data System [BI-RADS]).
To create their model, the authors used population-based data from the Breast Cancer Surveillance Consortium and the Surveillance, Epidemiology, and End Results (SEER) of the National Cancer Institute.
The women in the model had varying risk factors for breast cancer. The model assumed that they all started out as healthy, but could ultimately fall into 1 of 6 categories: remain healthy; develop ductal carcinoma in situ; develop localized invasive breast cancer; develop regional invasive breast cancer; develop distant invasive breast cancer; or die from invasive breast cancer or other causes.
For each scenario, the authors calculated the number of women who would need to be screened over 10 years to prevent 1 death from breast cancer. They also estimated the costs for each frequency of mammography for each quality-adjusted life-year (QALY) gained.
Varying Benefit and Cost Effectiveness
Annual mammography was not found to be cost effective for any group, regardless of age or breast density. At a cost-effectiveness threshold of $100,000 per QALY gained, biennial mammography was found to be cost effective for women 40 to 79 years of age with BI-RADS category 3 or 4 breast density, or for women 50 to 69 years of age with category 2 density.
It was also cost effective for women 60 to 79 years of age with category 1 density and either a family history of breast cancer or a previous breast biopsy, and for all women between the ages of 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density.
When using a cost-effectiveness threshold of $50,000 per QALY gained, biennial mammography was cost effective for women 40 to 49 years of age with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer.
The authors observed a similar pattern when analyzing the benefits only of mammography. Fewer women needed to be screened to prevent 1 death from breast cancer as age or breast density increased. As an example, when mammography was performed every 3 to 4 years for 10 years, preventing 1 death from breast cancer required 337 women 70 to 79 years of age with BI-RADS category 4 breast density to be screened. This was compared with 4870 women 40 to 49 years of age with category 2 breast density.
When mammography was performed biennially instead of every 3 to 4 years for 10 years, preventing 1 breast cancer death required the screening of 2041 women 60 to 69 years of age with category 4 breast density. This was compared with 12,195 women 40 to 49 years of age with category 2 breast density.
The study was funded by Eli Lilly, the Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and the Breast Cancer Surveillance Consortium.
Ann Intern Med. 2011;155:10-20. Abstract