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Polygenic Risk Scores Improve Breast Cancer Screening

April 4, 2024
in Health
Polygenic Risk Scores Improve Breast Cancer Screening
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TOPLINE:

Using polygenic risk scores along with positive family histories and breast cancer-associated gene mutations improves risk stratification for breast cancer screening.

METHODOLOGY:

A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: Before, during, and after screening age.

TAKEAWAY:

Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.

IN PRACTICE:

This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.

SOURCE:

The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.

LIMITATIONS:

The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.

DISCLOSURES:

The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]

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Copyright for syndicated content belongs to the linked Source : Medscape – https://www.medscape.com/viewarticle/polygenic-risk-scores-improve-breast-cancer-screening-2024a10006ag

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