scholarly journals Clustering of known low and moderate risk alleles rather than a novel recessive high‐risk gene in non‐ BRCA1 /2 sib trios affected with breast cancer

2020 ◽  
Vol 147 (10) ◽  
pp. 2708-2716
Author(s):  
Florentine S. Hilbers ◽  
Peter J. Hof ◽  
Caro M. Meijers ◽  
Hailiang Mei ◽  
Kyriaki Michailidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Moderate Risk ◽  
Risk Gene ◽  
Risk Alleles

scholarly journals Risk-Adapted Postmastectomy Radiotherapy Decision Based on Prognostic Nomogram for pT1-2N1M0 Breast Cancer: A Multicenter Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Ming Li ◽  
Jinbo Yue ◽  
Xiangbo Wan ◽  
Bin Hua ◽  
Qiuan Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Locoregional Recurrence ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Moderate Risk ◽  
Primary Tumor Site ◽  
Free Survival ◽  
Significant Difference

PurposeThe aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer.Methods and MaterialsA total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model.ResultsWith the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P<0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS.ConclusionsThe proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.

scholarly journals Prevalence and Clinicopathological Characteristics of Moderate and High-Penetrance Genes in Non-BRCA1/2 Breast Cancer High-Risk Spanish Families

2021 ◽  
Vol 11 (6) ◽  
pp. 548
Author(s):  
Maria Fonfria ◽  
Inmaculada de Juan Jiménez ◽  
Isabel Tena ◽  
Isabel Chirivella ◽  
Paula Richart-Aznar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Clinical Characteristics ◽  
Single Gene ◽  
Clinicopathological Characteristics ◽  
Loss Of Function ◽  
Moderate Risk ◽  
Risk Genes ◽  
Pathogenic Variants ◽  
Index Cases

(1) Background: Over the last decade, genetic counseling clinics have moved from single-gene sequencing to multigene panel sequencing. Multiple genes related to a moderate risk of breast cancer (BC) have emerged, although many questions remain regarding the risks and clinical features associated with these genes. (2) Methods: Ninety-six BC index cases (ICs) with high-risk features for hereditary breast and ovarian cancer (HBOC) and with a previous uninformative result for BRCA1/2 were tested with a panel of 41 genes associated with BC risk. The frequency of pathogenic variants (PVs) was related to the clinical characteristics of BC. (3) Results: We detected a PV rate of 13.5% (excluding two cases each of BRCA1 and MUTYH). Among the 95 assessed cases, 17 PVs were identified in 16 ICs, as follows: BRCA1 (n = 2), CHEK2 (n = 3), ATM (n = 5), MUTYH (n = 2), TP53 (n = 2), BRIP1 (n = 1), CASP8 (n = 1), and MSH2 (n = 1). We also identified a novel loss-of-function variant in CASP8, a candidate gene for increased BC risk. There was no evidence that the clinical characteristics of BC might be related to a higher chance of identifying a PV. (4) Conclusions: In our cohort, which was enriched with families with a high number of BC cases, a high proportion of mutations in ATM and CHEK2 were identified. The clinical characteristics of BC associated with moderate-risk genes were different from those related to BRCA1/2 genes.

Estimation of additional MRI resources needed in British Columbia for screening high-risk women for breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 51-51
Author(s):  
Rasika Rajapakshe ◽  
Christabelle Bitgood ◽  
Steven McAvoy ◽  
Cynthia Araujo ◽  
Paula Gordon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
British Columbia ◽  
Family History ◽  
High Risk ◽  
Screening Mammography ◽  
Low Risk ◽  
Moderate Risk ◽  
High Risk Women ◽  
Risk Distribution ◽  
Victoria General Hospital

51 Background: Screening women at high risk with MRI has been shown to detect breast cancer at an early stage. Therefore, MRI screening has been recommended in the UK and USA for women who are at a high risk of developing breast cancer. However, there is no information available in the province of British Columbia (BC) about the number of women who have a high risk of developing breast cancer. Therefore, we carried out a study to estimate the breast cancer risk distribution in three sample populations in BC using Tyrer-Cuzick (TC) risk prediction model so that additional resource requirement for MRI breast screening can be calculated. Methods: A survey questionnaire was designed based on the TC model, which includes family history, hormonal factors, and benign breast disease. Additional questions also include factors that are used in other models (Gail, Claus, and BCRAPRO) as well as factors that may be included in the future. Women were recruited by staff and volunteers at three screening mammography clinics: Kelowna, Victoria General Hospital, and BC Women’s Health Centre in Vancouver. The survey was available to women to complete on the web, by phone, or on paper. An online database was constructed to store and query the data. The 10-year risk of developing breast cancer for each woman was calculated using the Tyrer-Cuzick IBIS Risk Evaluator software and the risk distribution of the survey population was analyzed. Results: Data from 3,200 women recruited from three sites, gives a risk distribution showing 2.6% are at high risk of developing breast cancer, 31.2% are at moderate risk, and 66.2% are at low risk. Based on NICE guidelines (UK), high risk is defined as having a 10-year risk of greater than 8%, moderate risk as 3-8%, and low risk as less than 3%. Extrapolating this to the approximately 500,000 women who are eligible to attend for screening mammography in BC, 13,000 women are considered at high risk. Conclusions: Our results indicate that 2.6% of women ages 40-79 attending screening mammography in BC may have a very high risk of developing breast cancer based on personal and family history. Based on a 14-hour work day, three additional MRI scanners would be required to implement MRI screening for these high-risk women in BC.

scholarly journals From BRCA1 to Polygenic Risk Scores: Mutation-Associated Risks in Breast Cancer-Related Genes

Breast Care ◽  
2021 ◽  
pp. 1-12
Author(s):  
Emma R. Woodward ◽  
Elke M. van Veen ◽  
D. Gareth Evans
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Reproductive Factors ◽  
Risk Scores ◽  
Clinical Indication ◽  
Nucleotide Polymorphisms ◽  
Moderate Risk ◽  
Risk Genes ◽  
Increased Risk ◽  
Gene Panels

<b><i>Background:</i></b> There has been huge progress over the last 30 years in identifying the familial component of breast cancer. <b><i>Summary:</i></b> Currently around 20% is explained by the high-risk genes <i>BRCA1</i> and <i>BRCA2</i>, a further 2% by other high-penetrance genes, and around 5% by the moderate risk genes <i>ATM</i> and<i> CHEK2</i>. In contrast, the more than 300 low-penetrance single-nucleotide polymorphisms (SNP) now account for around 28% and they are predicted to account for most of the remaining 45% yet to be found. Even for high-risk genes which confer a 40–90% risk of breast cancer, these SNP can substantially affect the level of breast cancer risk. Indeed, the strength of family history and hormonal and reproductive factors is very important in assessing risk even for a BRCA carrier. The risks of contralateral breast cancer are also affected by SNP as well as by the presence of high or moderate risk genes. Genetic testing using gene panels is now commonplace. <b><i>Key-Messages:</i></b> There is a need for a more parsimonious approach to panels only testing those genes with a definite 2-fold increased risk and only testing those genes with challenging management implications, such as <i>CDH1</i> and <i>TP53</i>, when there is strong clinical indication to do so. Testing of SNP alongside genes is likely to provide a more accurate risk assessment.

scholarly journals Breast Cancer in Indian Women: Genetic Risk Factors and Predictive Biomarkers

2019 ◽  
Vol 55 (01) ◽  
pp. 034-047
Author(s):  
Sunita Saxena ◽  
Anurupa Chakraborty ◽  
Mishi Kaushal ◽  
R. S. Mohil ◽  
A. K. Mishra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
High Risk ◽  
Advanced Breast Cancer ◽  
Young Women ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Indian Women ◽  
Risk Alleles

AbstractBreast cancer is the most common cancer among Indian women with a significant increase in incidence in young women. To identify risk factors for breast cancer in young women, study of BRCA1 and BRCA2 germ line mutations was done in a cohort of 204 Indian breast cancer patients. The study showed a total of 18 mutations in 2.94% of the tested patients, 44% BRCA1 and 78% BRCA2 mutations were found unique to the Indian population. Association of low penetrance genes mainly CYP17, VDR gene and AR-CAG repeat polymorphisms with breast cancer risk showed CYP17 A2 and VDR Poly-A L as high risk alleles, the risk of developing breast cancer among women carrying three high-risk alleles is 4.68 (95% confidence interval [CI]: 0.77–28.0; p for trend = 0.10) compared with women carrying none. CYP17 A2 allele was also found associated with development of breast cancer at young age and can also serve as a target for therapy. Betel quid chewing has been found as a significant and independent risk factor for developing breast cancer in North East Indian women which induces genetic alterations leading to breast carcinogenesis. Studies to assess the predictive role of various tumor markers showed that expression of p-glycoprotein in pretreatment biopsy predicts a poor clinical response to neoadjuvant chemotherapy (NACT) in patients having locally advanced breast cancer. The chemotherapy-induced toxicity (vomiting and alopecia) correlated significantly with clinical and immunohistochemical response (reduction in bcl2/bax ratio) and were found to be a cost-effective and reliable predictor of response to NACT. Androgen receptor (AR) has been identified as independent predictive marker for response to NACT in locally advanced breast cancer cases and can serve as novel therapeutic target for triple negative breast cancers.

scholarly journals Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population

2018 ◽  
Vol 91 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Iulian Gabriel Goidescu ◽  
Gabriela Caracostea ◽  
Dan Tudor Eniu ◽  
Florin Vasile Stamatian
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Deleterious Mutations ◽  
Cancer Genes ◽  
Moderate Risk ◽  
Risk Genes ◽  
Panel Testing ◽  
Pathogenic Mutations ◽  
Multigene Panel

Aim. Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance.Methods. Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing.Results. 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases.Conclusion. Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive.

scholarly journals Performance of TyrerCuzick Model for Breast Cancer Risk Assessment among Pakistan’s Females

2021 ◽  
pp. 73-79
Author(s):  
Rufina Soomro ◽  
Rabia Niaz
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Mammographic Density ◽  
Breast Cancer Incidence ◽  
Menopausal Status ◽  
Low Risk ◽  
Moderate Risk ◽  
Breast Cancer Risk Assessment ◽  
High Mammographic Density

Background: Breast cancer incidence is highest in Pakistan among Asian countries. The known risk factors are family history, hormonal exposure, benign proliferative diseases, and high mammographic density which are included in the TyrerCuzick model. The model needs validation studies to implement in prediction, screening, and prevention strategies among different populations. This study aims to validate the TyrerCuzick model for Pakistan's females. Methods and Materials: A total of 317 biopsy-proven breast cancer patients from the breast surgery clinic at Liaquat National Hospital were included. The 10 years risk score is calculated by applying the TyrerCuzick model software. Subcategories of low risk <2%, moderate risk 2-7%, and high risk >8% were identified. Further risk group stratification is done to find the association with individual factors i.e., age group, menopausal status, family history, and mammographic density. Results: The mean TyrerCuzick score was low to moderate i.e. 2.23±1.66. The score was distributed as low risk 174(54.9%), moderate risk 137(43.2%), and high risk 6(1.9%). Low risk was observed among 116(81.7%) of less than 50 years old, 105(78.9%) premenopausal, 113(59.8%) with no family history, and 120 patients (59.7%) with low mammographic density. Most of the moderate risk was found in 113(64.6%) of more than 50 years old, 109(60.2%) with postmenopausal, 24(61.5%) with family history, 58(50%) with high mammographic density respectively. Conclusion: The TyrerCuzick model can predict risk for developing breast cancer among Pakistan’s femalesclose to accurate among older age, postmenopausal, family history of breast cancer, and high mammographic density.

Colorectal cancer knowledge and screening rates are lower than for breast cancer even in individuals at high risk of cancer

2001 ◽  
Vol 120 (5) ◽  
pp. A741-A741
Author(s):  
P ANG ◽  
D SCHRAG ◽  
K SCHNEIDER ◽  
K SHANNON ◽  
J JOHNSON ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Knowledge ◽  
Risk Of Cancer
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