Study: Breast cancer screening should be tailored to a woman’s risk factors and breast density

IN DEPTH REVIEW OF RESEARCH

Study background:

The 2016 U.S. Preventive Services Task Force (USPSTF) made the controversial recommendation that women aged 50-74 should get screening mammograms every other year, rather than annually. However, do all women in this age group benefit from the same screening mammogram regime? Amy Trentham-Dietz and her colleagues from the University of Wisconsin Carbone Cancer Center and other institutions published work in the Annals of Internal Medicine that addresses this question.

Researchers of this study wanted to know:

Can a woman’s breast density and breast cancer risk be used to determine the optimal time between her screening mammograms?

Population(s) looked at in the study:

Researchers from the Cancer Intervention and Surveillance Modeling Network and the Breast Cancer Surveillance Consortium used three well-established models (Models E, GE, and W) to predict the benefits and harms of screening mammograms for women 50 years and older with various combinations of breast cancer risk and breast densities. This model used data collected from 1975-2010 by the Surveillance, Epidemiology, and End Results (SEER) program. The women modeled were at average or moderate (not greater than four times increased risk) risk for breast cancer. Factors leading to a moderate risk of breast cancer included postmenopausal obesity, a history of benign breast biopsies, and a history of lobular carcinoma in situ (LCIS).  Note that moderate breast cancer risk is not as great as the risk of women with BRCA mutations.  Benefits measured were breast cancer deaths avoided due to screening, and quality-adjusted life-years. Harmful outcomes measured were false positive mammograms, benign biopsies, and overdiagnosis (defined as “screen-detected cancer that would not have been diagnosed in a woman's lifetime in the absence of mammography”).

Study findings: 

1. Using a computer model, researchers predict that screening mammograms every three years for women who are age 50 and older with average risk for breast cancer and low breast density produces similar or better benefits and harms compared to women who are at average risk and get mammograms every two years.
   • The model predicts that approximately 150 false-positive mammograms will occur to avoid one breast cancer death if women at average risk who have low breast density are screened every two years. It also predicts that with triennial screening, approximately 125 false-positive mammograms will occur to avoid one death due to breast cancer. This means that according to the model predictions, screening women at average risk every three years will lessen the number that receive false-positive mammograms to save one life.
2. Using a computer model, researchers predict that screening mammograms every year for women who are age 50 and older with higher risk for breast cancer and high breast density produces similar or better benefits and harms compared to women who are at average risk and get mammograms every two years.
   • This means that annual screening mammograms are more beneficial for women with high breast density and high risk for breast cancer, because they have a better balance of benefits (more breast cancer deaths avoided) and harms (false-positive mammograms, benign biopsies) than women at average risk who get mammograms every two years.

Limitations:

Because this study only included information from women who were 50 years and older, the findings do not apply to younger women. Nor did it look at women who are at higher risk of breast cancer due to a genetic mutation such as BRCA that increases breast cancer risk. And finally, because these results are predicted from a computer model, it assumes that patients will adhere to the screening schedule, which may not be the case for all women.  

The conclusions also hinge on how the authors define harm and whether patients would use the same definition. For some women, being called back for additional screening or having a benign biopsy may appear to be a harm.  Other women may prefer to have this additional screening, despite the risk that a detected abnormality turns out to be something other than cancer. This points to a need for personalizing breast screening, not only based on a patient’s risk for breast cancer, but also on her preferences.

It is important to note that this paper used current USPSTF guidelines for breast cancer screening in average risk women as a starting point. These guidelines are controversial and differ from others. Guidelines of numerous other organizations, including the American Cancer Society (ACS), the National Comprehensive Cancer Network (NCCN), the American Medical Association (AMA), the American College of Radiology (ACR), and the American Congress of Obstetricians and Gynecologists (ACOG) recommend annual screening mammograms beginning at younger ages—the ACS recommends age 45, while the other organizations recommend age 40. Recently, the NCCN added that women and their doctors consider using 3D mammography (tomosynthesis), which is not addressed in this study. 

Separate guidelines exist for women known to be at high risk for breast cancer due to mutations in BRCA or other genes associated with increased cancer risk, a strong family history of breast cancer, and/or history of radiation treatment to the chest. In some cases, guidelines recommend combining magnetic resonance imaging (MRI) with mammography. These types of screening were not addressed by this study.

Conclusions:

This study suggests that a woman’s breast density and breast cancer risk can be used to tailor her breast cancer screening interval. These findings are not definitive, because they used computer models to predict the results of being screened at one-, two-, or three-year intervals. However, this research opens discussion on how to tailor screening to benefit each patient individually. Additionally, more work needs to be done to address the limitations of the study, including women who are younger and have mutations in genes that increase cancer risk.

While this study is a step towards personalizing breast cancer screening for women who do not have mutations in BRCA or other genes that increase cancer risk, more work is needed to correctly identify women who would benefit from increased screening. Patients and their health care providers should work together to determine a patients’ optimal screening regimen based on personal and family history of cancer, as well as the patient’s tolerance for the risk of false positives and/or benign biopsies.     

Posted 10/18/16

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References

Trentham-Dietz A, Kerlikowske K, Stout NK, et al. “Tailoring Breast Cancer Screening Intervals by Breast Density and Risk for Women Aged 50 Years or Older: Collaborative Modeling of Screening Outcomes.” Annals of Internal Medicine. Published online first on August 23, 2016.