Communicating polygenic risk scores in the familial breast cancer clinic

2021 ◽  
Author(s):  
Kuheli Das Gupta ◽  
Gillian Gregory ◽  
Bettina Meiser ◽  
Rajneesh Kaur ◽  
Maatje Scheepers-Joynt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Cancer Clinic

scholarly journals The importance of Ethnicity: are breast cancer Polygenic Risk Scores ready for women who are not of white European origin?

2021 ◽  
Author(s):  
D. Gareth Evans ◽  
Elke M Veen ◽  
Helen Byers ◽  
Eleanor Roberts ◽  
Anthony Howell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Scores ◽  
European Origin ◽  
Polygenic Risk

scholarly journals Polygenic risk, susceptibility genes, and breast cancer over the life course

2020 ◽  
Author(s):  
Nina Mars ◽  
Elisabeth Widén ◽  
Sini Kerminen ◽  
Tuomo Meretoja ◽  
Matti Pirinen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Clinical Decision Making ◽  
Breast Cancer Mortality ◽  
Breast Cancer Incidence ◽  
Positive Family History ◽  
Risk Scores ◽  
Limited Information ◽  
Polygenic Risk ◽  
Fold Enrichment

ABSTRACTPolygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their clinical applicability. We set out to study how PRS could help in clinical decision making. Among 99,969 women in the FinnGen study with 6,879 breast cancer cases, the PRS was associated not only with breast cancer incidence but also with a range of breast cancer-related endpoints. Women with a breast cancer PRS above the 90th percentile had both higher breast cancer mortality (HR 2.40, 95%CI 1.82-3.17) and higher risk for non-localized disease at diagnosis (HR 2.94, 95%CI 2.63-3.28), compared to those with PRS <80th percentile. The PRS modified the breast cancer risk of two high-impact frameshift risk variants. Women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 263 carriers) and an average PRS (20-80th percentile) had a lifetime risk of breast cancer at 58% (95%CI 50-66%), which increased to 85% (70-100%) with a high PRS (>90th percentile), and decreased to 27% (15-39%) with a low PRS (<20th percentile). Similarly, for c.1100delC in CHEK2 (3.7-fold enrichment; 1,543 carriers), the respective lifetime risks were 27% (95%CI 25-30%), 59% (52-67%), and 18% (13-22%). Among breast cancer cases, a PRS >90th percentile was associated with risk of contralateral breast cancer with HR 1.66 (95%CI 1.24-2.22). Finally, the PRS significantly refined the risk assessment of women with first-degree relatives diagnosed with breast cancer, i.e. the combination of high PRS (>90th percentile) and a positive family-history was associated with a 2.33-fold elevated risk (95%CI 1.57-3.46) compared to a positive family history alone. These findings demonstrate opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members.

scholarly journals The role of polygenic risk and susceptibility genes in breast cancer over the course of life

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nina Mars ◽  
◽  
Elisabeth Widén ◽  
Sini Kerminen ◽  
Tuomo Meretoja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Positive Family History ◽  
Breast Cancer Diagnosis ◽  
Risk Scores ◽  
Limited Information ◽  
Breast Cancer Patients ◽  
Polygenic Risk ◽  
First Degree Relatives ◽  
Fold Enrichment

AbstractPolygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10–90th percentile) have a lifetime risk of breast cancer at 55% (95% CI 49–61%), which increases to 84% (71–97%) with a high PRS ( > 90th percentile), and decreases to 49% (30–68%) with a low PRS ( < 10th percentile). Similarly, for c.1100delC in CHEK2 (3.7–fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27–32%), 59% (52–66%), and 9% (5–14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members.

scholarly journals Deep neural network improves the estimation of polygenic risk scores for breast cancer

2020 ◽  
Author(s):  
Adrien Badré ◽  
Li Zhang ◽  
Wellington Muchero ◽  
Justin C. Reynolds ◽  
Chongle Pan
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Deep Neural Network ◽  
Risk Scores ◽  
Polygenic Risk

Impact of Personalized Genetic Breast Cancer Risk Estimation With Polygenic Risk Scores on Preventive Endocrine Therapy Intention and Uptake

2020 ◽  
pp. canprevres.0154.2020
Author(s):  
Julian O. Kim ◽  
Daniel J. Schaid ◽  
Celine M. Vachon ◽  
Andrew Cooke ◽  
Fergus J. Couch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Endocrine Therapy ◽  
Risk Estimation ◽  
Risk Scores ◽  
Polygenic Risk

scholarly journals A Role for Common Genomic Variants in the Assessment of Familial Breast Cancer

2012 ◽  
Vol 30 (35) ◽  
pp. 4330-4336 ◽  
Author(s):  
Sarah Sawyer ◽  
Gillian Mitchell ◽  
Joanne McKinley ◽  
Georgia Chenevix-Trench ◽  
Jonathan Beesley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Familial Breast Cancer ◽  
Brca2 Mutation ◽  
Mutation Screening ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Genomic Variants ◽  
Risk Distribution

Purpose Genome-wide association studies have identified common genomic variants associated with increased susceptibility to breast cancer. In the general population, the risk associated with these known variants seems insufficient to inform clinical management. Their contribution to the development of familial breast cancer is less clear. Patients and Methods We studied 1,143 women with breast cancer who had completed BRCA1 and BRCA2 mutation screening as a result of a high risk for hereditary breast cancer. Genotyping of 22 breast cancer–associated genomic variants was performed. A polygenic risk score (PRS), calculated as the sum of the log odds ratios for each allele, was compared with the same metric in 892 controls from the Australian Ovarian Cancer Study. The clinical features associated with the high and low ends of the polygenic risk distribution were compared. Results Women affected by familial breast cancer had a highly significant excess of risk alleles compared with controls (P = 1.0 × 10−16). Polygenic risk (measured by the PRS) was greater in women who tested negative for a BRCA1 or BRCA2 mutation compared with mutation carriers (P = 2.3 × 10−6). Non-BRCA1/2 women in the top quartile of the polygenic risk distribution were more likely to have had early-onset breast cancer (< 30 years of age, odds ratio [OR]= 3.37, P = .03) and had a higher rate of second breast cancer (OR 1.96, P = .02) compared with women with low polygenic risk. Conclusion Genetic testing for common risk variants in women undergoing assessment for familial breast cancer may identify a distinct group of high-risk women in whom the role of risk-reducing interventions should be explored.

scholarly journals Polygenic risk scores for prediction of breast cancer risk in Asian populations

2021 ◽  
Author(s):  
Weang-Kee Ho ◽  
Mei-Chee Tai ◽  
Joe Dennis ◽  
Xiang Shu ◽  
Jingmei Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Scores ◽  
Polygenic Risk ◽  
Asian Populations
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