Abstract P4-03-04: Genetic testing contributes significantly to improved identification of women eligible for increased breast cancer screening compared to the Tyrer-Cuzick risk model
Authors: Gorringe HM , Rosenthal E , Morris B , Manley S 
Published: May 2019

Background: Increased screening, including breast MRI, is recommended for women carrying pathogenic variants (PVs) in certain breast cancer risk genes, as well as women with an estimated remaining lifetime risk of breast cancer &gt;20% based on risk models such as Tyrer-Cuzick (TC). We determined the extent to which genetic testing identifies women as candidates for increased screening who would not have been flagged using the TC model.

Methods: We evaluated 100,318 women who underwent clinical genetic testing for suspicion of hereditary breast cancer risk between June 2017 and June 2018. Testing with a 28 gene pan-cancer panel included 5 established breast cancer risk genes for which there are National Comprehensive Cancer Network (NCCN) recommendations for increased screening including breast MRI (BRCA1, BRCA2, ATM, CHEK2, PALB2). A remaining lifetime breast cancer risk estimate was calculated using TC V 7.02, unless the woman was ineligible due to a breast cancer diagnosis, age over 85, or if the sample was submitted without any of the necessary TC data. Risk estimates were calculated entering the BRCA1/2 status as unknown.

Results: 4,640 (4.6%) women were found to carry a PV in one of the five genes, with 57.0% of the PVs in BRCA1 or BRCA2, and 43.0% in ATM, CHEK2 or PALB2. Among the women with a PV, 1,479 (31.9%) had a diagnosis of breast cancer, and 407 (8.8%) were ineligible for TC for another reason. A TC risk estimate was calculated for 2,754 women, of whom 41.5% did not meet the 20% threshold using TC. Table 1 shows the breakdown for each gene by age at the time of testing. Women with PVs in BRCA1 were the least likely to have a TC score &lt;20% and those with PVs in BRCA2 and ATM were the most likely to fall below the 20% threshold. Remaining lifetime risk declined with age in all groups.

Table 1.Percentage of women carrying PVs in breast cancer risk genes with a remaining lifetime risk of breast cancer risk estimated at &lt;20% by Tyrer-Cuzick.Age at time of testingBRCA1 (N=1215)BRCA2 (N=1432)ATM (N=609)CHEK2 (N=971)PALB2 (N=413)&lt;2014.8%11.1%0.0%33.3% 20-2922.0%27.3%29.5%28.4%19.1%30-3928.7%38.1%30.3%36.4%22.6%40-4938.4%48.8%47.7%42.5%50.0%50-5949.4%62.7%64.3%52.3%44.4%60-6987.5%78.8%71.9%77.8%71.4%70-79--100.0%100.0%100.0%100.0%80+100.0%--------All ages33.6%45.7%46.3%42.6%37.4%

Conclusions: Among the women included in this analysis, the TC model failed to identify approximately 40% of women eligible for high risk breast cancer screening due to PVs in breast cancer risk genes. This demonstrates that risk models based on clinical factors alone will fail to identify a significant fraction of women who are candidates for modified medical management. Additionally, it may be desirable to re-evaluate setting thresholds based on remaining lifetime risk, since this dramatically reduces the likelihood that high-risk women will be flagged for increased screening at older ages, when their immediate risk of a breast cancer diagnosis is likely to be highest.

Citation Format: Gorringe HM, Rosenthal E, Morris B, Manley S. Genetic testing contributes significantly to improved identification of women eligible for increased breast cancer screening compared to the Tyrer-Cuzick risk model [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-04.