After several years of upheaval over the best way to conduct breast cancer screening, researchers are working to find clarity over when women should begin getting mammograms, how often, and at what cost. A pair of new studies clears up some of the uncertainty by finding that women who have a mother or sister diagnosed with breast cancer, or those who have unusually dense breast tissue, should have their first test at age 40 and repeat the exam at least once every other year.
For these women, who face at least twice the average risk of developing breast cancer in their 40s, the benefits of routine screening between the ages of 40 and 49 outweigh the risk of false alarms and unnecessary work-ups that might otherwise put them at greater risk than doing nothing, researchers report in Tuesday's edition of Annals of Internal Medicine.
Of the various recommendations put forth by the U.S. Preventive Services Task Force in 2009, none generated more ire than the suggestion that annual mammograms could do more harm than good for most forty-something women, who are far less likely than older women to get breast cancer. The task force advised women in their 40s to talk with their doctors and make individualized decisions about whether to get a mammogram every other year at most.
The new research was designed to identify women who could benefit the most from having mammograms early and often.
In the process, the doctors and other experts who worked on the studies pushed a relatively new risk factor - breast density - to the forefront in the calculations a woman and her physician make as they decide how assiduously to check for breast cancer.
The two studies arrive at their conclusions through different means. One involved combining and analyzing data from 61 studies that have already been published. The other used computer models to predict the health outcomes of about 44,000 simulated women who had their first mammogram at 50. They then ran the same women through a simulation in which they began screening at 40 and compared the rates of false alarms, breast cancer diagnoses and mortality in both groups.
"The fog is clearing," said Dr. Diana Petitti, who worked on the 2009 Preventive Services Task Force study. "Personalized breast screening recommendations are better."
The recommendations from the U.S. Preventive Services Task Force, an independent panel of health experts that advises the federal government, upended the long- and fiercely held beliefs of most practitioners and breast cancer activists by suggesting that women older than 50 should have a mammogram every two years instead of annually, and that most women in their 40s should skip the test altogether. Until then, women over 40 were routinely advised to have a mammogram once a year.
The latest studies push further away from what many have since called "one size fits all" medicine and toward an approach more tailored to the individual patient and her risks. Dr. Otis Brawley, chief medical officer for the American Cancer Society, likened the effort to identify who can benefit most from mammogram screening to the type of "personalized medicine" that is used to identify patients who will benefit the most from intensive efforts to forestall heart disease.
Using assumptions that undergirded the controversial 2009 Preventive Services report, researchers found that among women 50 to 74, for every breast cancer death averted by screening, 146 women received a false-positive reading on a mammogram. In addition, for every year of life that a woman gained because her breast cancer had been detected early by mammogram, there were 8.3 false positives that led to unnecessary biopsies, weeks of worry and in some cases surgical complications.
Shifting their focus to simulated women between the ages of 40 and 49, the researchers found that the only ones who stood to benefit to a similar degree were those whose breast cancer risk was roughly double the norm for their age group.
The companion study fills out the picture by pinpointing ways to assess a woman's breast-cancer risk in her 40s. For instance, the researchers showed that having a first-degree relative - a mother or sister - with a breast cancer diagnosis more than doubles the woman's own risk of developing the disease. If she has two or more first-degree relatives with breast cancer, her risk goes up by nearly a factor of four.
The study also found that having breasts made up of substantially more glandular tissue rather than fat was enough to double a woman's breast cancer risk in her 40s. However, this also makes breast cancer harder to find on a mammogram, because cancerous tumors do not show up as readily against a backdrop of glandular tissue as they do against fat.
The researchers found that women who have had breast biopsies that turned out to be benign have an 80 percent greater risk of getting the disease in their 40s; women on oral contraceptives have a 30 percent increased risk; women who have never given birth have a 25 percent greater risk; and women who had their first child after age 30 have a 20 percent increased risk.
In an editorial accompanying the two studies, Brawley said the findings about dense breasts create "several conundrums," not least that their mammograms are difficult to interpret. If breast density becomes a factor that drives how often women should be screened, he wrote, future guidelines may include the recommendation that all women get a baseline mammogram at age 40.
Dr. Patricia Ganz, a breast cancer specialist at the University of California, Los Angeles, said the studies will help in the development of "user-friendly ways that a primary-care physician can start that conversation" about a woman's breast cancer risk and what steps she can take to address it. Ganz said the findings underscore the central importance of taking a family history - and of updating it as a woman (and her mother and sisters) age.
But Ganz, too, said the key risk factor of breast density needs better definition if it is to be a helpful guidepost to women and their doctors. Radiologists, who review mammograms, and primary-care doctors have no established standards or software that defines and grades breast density, she said, so sending all 40-year-old women to have their breast density assessed would be premature.
"It's not really ready for prime time," she said.