ICARE Newsletter Fall 2021 

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Polygenic Risk Scores and Breast Cancer Risks: BRCA1/2, PALB2, CHEK2, ATM , and beyond!

A recent study found use of a polygenic risk score (PRS) modified the estimated risk
of breast cancer among both carriers and non-carriers of inherited breast cancer
predisposition genes. Taking PRS into account, more than 95% of BRCA1, BRCA2,
and PALB2 carriers had greater than 20% lifetime risks of breast cancer. In contrast,
among ATM and CHEK2 carriers without a first-degree relative with breast cancer,
proportions with a 20% or higher lifetime risk were 52.5% and 69.7%, respectively,
whereas higher proportions with a 20% or higher risk were seen in those with a
first-degree relative with breast cancer (78.8% and 89.9%, respectively). The
authors suggest that incorporating PRS into breast cancer risk estimation may help
identify greater than 30% of CHEK2 and nearly half of ATM carriers who have less
than a 20% lifetime risk for breast cancer and in whom breast MRI may not be
needed. This suggests the addition of PRS may prevent over screening and enable
personalized risk management approaches.
Gao, et al. J Clin Oncol. 2021 Aug. PMID: 34101481.