Study: Genetic testing can help identify who needs high-risk breast screening
Researchers in the WISDOM Study looked at women who had genetic testing and had an inherited mutation in a gene linked to increased breast cancer risk. When only risk factors other than genetic testing were considered, high-risk screening would not have been advised for most of these women. These results highlight how important genetic testing is to identify many women who need additional breast cancer screening. (posted 10/16/2026)
By: Piri Welcsh, PhD
Reviewed by: Allison Kurian, MD, MSc
RELEVANCE
Most relevant for: People concerned about their breast cancer risk who are considering genetic testing to guide breast screening.
It may also be relevant for:
- previvors
- people with a genetic mutation linked to cancer risk
- healthy people with average cancer risk
- people with a family history of cancer
Relevance: High
Strength of Science: Medium-High
Research Timeline: Human Research
What is this study about?
This study analyzed data from the national WISDOM Study (Women Informed to Screen Depending on Measures of Risk). This large clinical trial was designed to compare standard annual breast cancer screening with personalized, risk-based screening.
In this analysis, researchers grouped data from women with inherited mutations into three levels of breast cancer risk based on how much they increase risk compared to the general population: high-risk (, , , etc.), moderate-risk (, , etc.), and mild-risk I157T and S428F.
Researchers examined the degree to which information from genetic testing affected breast cancer screening recommendations.
| High-risk genes | Moderate-risk genes | Mild-risk mutations |
| , , , , , | , | I157T, S428F |
Why is this study important?
Breast screening recommendations are based on a person’s estimated risk. Breast cancer risk is calculated using tools that weigh various risk factors.
These calculated risk scores help to personalize screening recommendations. For example, while regular may be advised for average-risk individuals, high-risk individuals may need earlier, more frequent and additional screening, such as breast MRIs.
Because risk calculators consider different information, risk estimates may differ, leading to conflicting screening recommendations. The challenge is ensuring that people receive accurate risk assessments and the most appropriate screening recommendations.
Different factors used to calculate risk
Depending on the risk-assessment tool, information entered into a risk calculation may include several factors:
- Personal history
- Age, race/ethnicity, age at first menstrual period and menopause status.
- Reproductive history
- History of childbirth and age at first live birth.
- Genetics and family history
- Inherited genetic mutations (such as , , , ).
- Number of first-degree relatives (e.g., mother, sisters, daughters) diagnosed with breast cancer.
- Prior biopsies
- Number of past breast biopsies and results.
- Physical and imaging factors, such as breast density or surgeries (e.g., surgery to remove ovaries).
- Body Mass Index (BMI), hormone replacement therapy use and breast density assessed by .
- Polygenic risk score (PRS)
- PRS estimates a woman's chance of developing breast cancer over her lifetime, based on many small changes. PRS scores are different than genetic tests for risk. Although PRS scores were included in the Wisdom Study risk assessment, they are not widely used in medical care.
Study participants
The study included 712 women with an linked to breast cancer risk. Participants’ median age was 53, ranging from 46 to 62 years.
32% (232) had a mutation in a gene associated with a very high risk of breast cancer:
- 114 had a mutation in
- 62 had a mutation in
- 47 had a mutation in
- 5 had a mutation in
- 3 had a mutation in
- 1 had a mutation in
40% (278) had a mutation in a gene associated with a moderate risk of breast cancer:
- 166 had a mutation in
- 112 had a mutation in
28% (202) had one of the mutations, I157T or S428F, which increases breast cancer risk less than other mutations.
Researchers evaluated how screening recommendations from standard risk-assessment tools compared to recommendations based on genetic mutation risk levels (high, moderate or mild).
Study findings
Researchers found that most women with inherited mutations would not have received the same high-risk screening recommendation based only on other risk factors.
Among women with gene mutations associated with the highest breast cancer risk, fewer than 1% would have been placed in the high-risk screening group using clinical risk alone or clinical risk factors plus a polygenic risk score.
The risk model without genetic testing would have recommended that women with inherited mutations delay screening until age 50. It would also advise every two years for those aged 50 to 74, rather than more intensive screening.
What does this mean for me?
This study shows that standard breast cancer risk-assessment models, which include only family history, breast density, age and other clinical factors, may not recognize people who need high-risk breast cancer screening based on genetic testing results. Identifying an early is invaluable because it can affect decisions and recommendations about breast cancer screening, including if breast is needed.
Genetic testing can sometimes reveal risk that is not obvious from personal or family history alone. Ask your doctor or genetic counselor about genetic testing if you have a personal or family history of breast, ovarian, pancreatic or cancer, or if you are unsure whether you meet testing guidelines.
Some older genetic tests did not include all of the genes that now guide breast cancer screening recommendations. If you had genetic testing years ago, visit our Decision Checklist on Repeating Genetic Testing and ask your healthcare professional whether updated testing is appropriate.
Reference
Shieh Y, Heise RS, Madlensky L, et al. Impact of Population-Based Pathogenic Variant Testing on Risk-Based Breast Screening Recommendations: A Secondary Analysis of the WISDOM Study. JAMA Oncology. 2026;12(8):875–880.
Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
Share your thoughts on this XRAY review by taking our brief survey.
posted 11/16/2026
Questions To Ask Your Doctor
- Do I meet guidelines for genetic counseling or genetic testing based on my personal or family history?
- Would knowing I had a mutation in , , , , or another breast cancer gene change my screening plan?
- If I already had genetic testing, should I consider updated testing?
- If I have an , should my relatives consider genetic counseling or testing?
Share your thoughts!
How helpful was this XRAY review? We’d love to hear your feedback in our brief survey.