Starting breast-cancer screenings based on personal risk factors instead of age in women 40-49 years of age may significantly delay the detection of some early-stage breast cancers while also decreasing the number of false-positive mammograms and biopsies that reveal growths that are benign, according to new research from the University of Wisconsin School of Medicine and Public Health.

The results of the study, published today in the journal Radiology, question whether new guidelines that advocate mammography screening for women ages 40-49 based on breast cancer risk factors are sufficiently supported by existing risk prediction models.

Elizabeth Burnside
Beth Burnside, MD, MPH

Researchers conducted a retrospective, cross sectional study using a database of 20,539 prospectively read digital mammograms from 10,280 average-risk women aged 40-49. They found that screening women between the ages of 40-49 resulted in 50 screen-detected cancers, 1,787 false positive mammograms, and 384 benign biopsies.

Researchers then applied two hypothetical screening scenarios to that same data: an age-based scenario that would have initiated mammography screening based solely on a woman’s age (≥ 45); and a risk-based scenario that would have initiated screening using a risk prediction model. Risk prediction models use patient variables to calculate five- and 10-year invasive breast cancer risk—those variables include age, family history of breast cancer in a first degree relative, race/ethnicity, history of prior breast biopsy and breast density. Only women with a five-year risk of breast cancer greater than an average 50-year-old were considered to meet the threshold for the risk-based screening scenario. The results comparing the two hypothetical scenarios are as follows:

  • The age-based scenario included more mammographically detectable cancers (34/50) than the risk-based scenario (13/50). The age-based scenario (≥ 45) detected 68 percent of the cancers and the risk-based scenario detected 26 percent of the cancers in the 40-49 age group screened in practice.
  • Of the 16 undetected cancers in the age-based scenario, nine were invasive; Of the 37 undetected cancers under the risk-based scenario, 25 were invasive.
  • The risk-based scenario prompted fewer false positive mammograms (216) than the age-based scenario (899) and fewer benign biopsies (49) compared to the age-based scenario (175). The age-based scenario resulted in 3 percent of the false positive mammograms and 45.6 percent of the benign biopsies in the 40-49 age group screened in practice. The risk-based scenario resulted in 12.1 percent of the false positive mammograms and 12.8 percent of the benign biopsies in the 40-49 age group screened in practice.

According to Beth Burnside, MD, MPH, professor of radiology at UW University of Wisconsin School of Medicine and Public Health and the study’s principal investigator, the impact of a mammographically detectable cancer that goes undetected depends on the length of diagnostic delay and tumor behavior, the latter of which tends to be more aggressive in younger women. A substantial delay, she says, would make it more likely that a cancer would be detected clinically (according to symptoms), be larger, and be lymph-node positive.

“Almost all of the women in our study between the ages of 40-45 that developed a cancer detectable by mammography did not meet the threshold for risk-based screening at the time of their diagnosis and would not have been recommended for screening using the risk prediction model,” says Burnside.

Our study suggests that current risk models and thresholds may not identify young women who will get breast cancer and will not include these women in screening programs. The short-term outcomes of risk-based screening may lead to lengthy diagnostic delays, missing the opportunity for therapy in earlier, more treatable stages of the disease. These results suggest we need to continue to improve risk prediction models to make risk-based screening effective for women in this age group.”

Burnside acknowledges that the negative consequences of false-positive mammograms and unnecessary biopsies should not be discounted, as both can lead to short-term anxiety and increased health care costs.

Breast cancer is the leading cause of death for women 35-49 years old. Mammography has been shown to reduce mortality for women between the ages of 40-49, but the benefits-to-harms ratio is less favorable compared to women in older age ranges.

The United States Preventive Services Task Force currently recommends that women 40-49 forgo screening unless they are motivated to do so by risk or values. However, the American Cancer Society encourages the option to screen starting at age 40, considering personal risk and recommends annual screening starting at 45. Finally, the American College of Radiology recommends annual screening starting at age 40.

“When choosing a screening strategy, physicians, patients and policy-makers will need to determine whether the trade-offs in both short- and long-term outcomes are acceptable, while at the same time weighing the practicality and complexity of each strategy,” says Burnside. “We hope this study will help motivate the research community to continue to improve risk prediction models while at the same time empowering women to advocate for the breast cancer screening decision they think is right for them.”