Switching mammography screening eligibility from age-based to risk-based criteria could improve mortality outcomes and reduce harms associated with false-positives, while offering patients a more tailored approach to care, U.S. research suggests.
“As our knowledge of individual risk factors grows, continuing with blanket recommendations becomes increasingly inefficient,” said first author Oguzhan Alagoz, PhD, from the University of Wisconsin-Madison. “Our study demonstrates that by utilizing available risk data, we can achieve a better balance of benefits and harms, maintaining or improving breast cancer survival rates while significantly reducing the burden of over-screening.”
Currently, general mammography screening guidelines target women at average breast cancer risk within a specified age range and do not consider the absolute risk of individual women at any given age. Risk-based screening is generally only used for women with significant risk factors associated with a lifetime breast cancer risk exceeding 20%, including those with pathogenic variants such as BRCA1/2.
However, Alagoz and co-authors explain in JAMA Network Open that the variation in breast cancer risk among the general population and the availability of validated tools to assess their risk in clinical practice, mean that there is an opportunity to develop more tailored screening programs.
They investigated this opportunity using computer simulated data for a cohort of U.S. women born in 1980 who were aged 40 years or older without a prior history of breast cancer.
“Ideally, randomized clinical trials would provide the strongest evidence to support widespread adoption of risk-based screening,” Alagoz told Inside Precision Medicine. “However, such trials require very large populations and long follow-up periods to reliably measure outcomes such as breast cancer mortality. In this context, simulation modeling plays an important complementary role. While models cannot replace clinical trials, they allow us to evaluate a wide range of screening strategies and long-term outcomes that are difficult to study empirically, so they serve as a ‘virtual laboratory.’”
The study compared 47 risk-based digital breast tomosynthesis screening strategies with three commonly recommended age-based strategies, measuring the number of breast cancer deaths averted relative to no screening as well as the rate of false positive screening results.
Women’s five-year absolute invasive breast cancer risk was categorized as low (≤0.80%), average (0.81–1.79%), intermediate (1.80–2.41%), or high (≥2.42%) according to the validated Breast Cancer Surveillance Consortium (BCSC) calculator, which incorporates factors such as age, race/ethnicity, family history, BMI, and breast density to generate a risk score. Women at the highest risk, such as those with a genetic variant or syndrome, a history of high-dose radiotherapy to the chest at a young age, and/or previous breast cancer, were excluded from the simulation because the researchers wanted to focus on optimizing screening for the general population.
Alagoz and colleagues report that, when compared with the U.S. Preventive Services Task Force recommended strategy of biennial age-based screening from ages 40–74 years (B40–74), nine of the 47 risk-based screening strategies modeled were associated with a comparable or greater number of breast cancer deaths averted relative to no screening (6.8–7.5 vs 6.8 per 1000 women) and 8–23% fewer false-positive recalls.
For example, a risk-based approach using biennial screening for women aged 55–74 years at low risk, aged 50–59 years at average risk, aged 45–54 years at intermediate risk, and aged 40–49 years at high risk combined with annual screening for women aged 60–74 years at average risk, aged 55–74 years at intermediate risk, and aged 50–74 years at high risk would be associated with 6% more breast cancer deaths averted than B40–74 (7.2 vs 6.8 per 1000 women) and 13% fewer false-positive recalls.
“Risk-based screening reduces false positives primarily by better aligning screening intensity with a woman’s likelihood of developing breast cancer,” said Alagoz. “Because false positives are strongly related to the number of screening exams performed, fewer unnecessary mammograms among low-risk women translate directly into fewer false-positive results overall.”
Alagoz noted that risk-based screening is becoming increasingly feasible because assessment tools such as the BCSC calculator are widely accessible and are being integrated into clinical workflows. However, he acknowledged that while most of the inputs used in the BCSC calculator are readily available, breast density requires a baseline mammogram.
He therefore suggested that “a practical implementation would likely involve women undergoing an initial age-based screen (e.g., at age 40 or 50) to establish their density and risk profile, which would then determine their subsequent screening intervals.”
Alagoz believes that “risk-based screening is poised to become a cornerstone of breast cancer prevention, offering a more nuanced and tailored approach to patient care.”
He concluded that “precision medicine is the future of medicine,” and the current study “confirms that precision medicine is not just about novel treatments, but also about the intelligent, personalized application of prevention strategies.”
