Abstract PD10-02: The influence of pathogenic variants in breast cancer predisposition genes on secondary breast cancer events in a prospectively collected cohort of breast cancer patients

2021 ◽  
Author(s):  
Judy C. Boughey ◽  
Tanya L. Hoskin ◽  
Siddhartha Yadav ◽  
Fergus J. Couch
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Predisposition ◽  
Breast Cancer Patients ◽  
Breast Cancer Predisposition ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Secondary Breast Cancer

scholarly journals Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast

2021 ◽  
Author(s):  
Siddhartha Yadav ◽  
Chunling Hu ◽  
Katherine L. Nathanson ◽  
Jeffrey N. Weitzel ◽  
David E. Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lobular Carcinoma ◽  
Population Based ◽  
Cancer Predisposition ◽  
Clinical Cohort ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Multigene Panel

PURPOSE To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS The study included 2,999 women with ILC from a population-based cohort and 3,796 women with ILC undergoing clinical multigene panel testing (clinical cohort). Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected female controls and between women with ILC and infiltrating ductal carcinoma (IDC). RESULTS The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analysis, CDH1 and BRCA2 PVs were associated with high risks of ILC (odds ratio [OR] > 4) and CHEK2, ATM, and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. Compared with IDC, CDH1 PVs were > 10-fold enriched, whereas PVs in BRCA1 were substantially reduced in ILC. CONCLUSION The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2, and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. Similar to IDC, multigene panel testing may be appropriate for women with ILC, but CDH1 should be specifically discussed because of low prevalence and gastric cancer risk.

Germline pathogenic variants in cancer predisposition genes among women with invasive lobular cancer of breast.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10581-10581
Author(s):  
Siddhartha Yadav ◽  
Chunling Hu ◽  
Susan M. Domchek ◽  
Jeffrey N. Weitzel ◽  
David Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Population Based ◽  
Cancer Predisposition ◽  
Clinical Cohort ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Multigene Panel Testing ◽  
Multigene Panel

10581 Background: The prevalence of germline pathogenic variants (PVs) in cancer predisposition genes among women with invasive lobular breast cancer (ILC) and the risk of ILC in PV carriers is not well-defined. Methods: The study included 2,999 women with ILC and 32,544 unaffected controls from a population-based cohort; 3,796 women with ILC and 20,323 women with invasive ductal carcinoma (IDC) undergoing clinical multigene panel testing (clinical cohort); and 125,748 exome sequences from unrelated women without a cancer diagnosis in the gnomAD 3.0 dataset. Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected controls in both cohorts and between women with ILC and IDC in the clinical cohort. Results: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analyses, CDH1 and BRCA2 PVs were associated with high risks of ILC (Odds ratio (OR) > 4), and CHEK2, ATM and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. PV frequencies in these genes in ILC and IDC were similar except for PV frequencies in BRCA1 and CDH1. Conclusions: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2 and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. While, multigene panel testing may be appropriate for women with ILC, CDH1 should be specifically discussed in the context of low prevalence and attendant gastric cancer risk.

scholarly journals Prevalence of RECQL germline variants in Pakistani early-onset and familial breast cancer patients

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Muhammad Usman Rashid ◽  
Noor Muhammad ◽  
Faiz Ali Khan ◽  
Umara Shehzad ◽  
Humaira Naeemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Onset ◽  
Familial Breast Cancer ◽  
High Performance ◽  
Breast Cancer Patients ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Breast Cancer Predisposition ◽  
Novel Variants

Abstract Background The RecQ Like Helicase (RECQL) gene has previously been shown to predispose to breast cancer mainly in European populations, in particular to estrogen receptor (ER) and/or progesterone receptor (PR) positive tumor. Here, we investigated the contribution of pathogenic RECQL germline variants to hereditary breast cancer in early-onset and familial breast cancer patients from Pakistan. Methods Comprehensive RECQL variant analysis was performed in 302 BRCA1 and BRCA2 negative patients with ER and/or PR positive breast tumors using denaturing high-performance liquid chromatography followed by DNA sequencing. Novel variants were classified using Sherloc guidelines. Results One novel pathogenic protein-truncating variant (p.W75*) was identified in a 37-year-old familial breast cancer patient. The pathogenic variant frequencies were 0.3% (1/302) in early-onset and familial breast cancer patients and 0.8% (1/133) in familial patients. Further, three novel variants of unknown significance, p.I141F, p.S182S, and p.C475C, were identified in familial breast cancer patients at the age of 47, 68, and 47 respectively. All variants were absent in 250 controls. Conclusions Our data suggest that the RECQL gene plays a negligible role in breast cancer predisposition in Pakistan.

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