Women’s Cancer Precision Panel
Overview
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Female breast cancer has now surpassed lung cancer as the leading cause of global cancer incidence in 2020, being the fifth leading cause of cancer mortality worldwide. Although breast cancer ranks among the cancer types with the highest heritability, pathogenic variants in high and moderate-penetrance genes are individually rare in the general population and are found approximately in 5-10% of unselected patients with breast cancer. Such variants are more likely to be present in patients who have a strong family history of breast cancer, younger patients and patients who have triple-negative breast cancer.
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Ovarian cancer ranks eighth in cancer incidence and cancer deaths among women worldwide. The strongest risk factor for ovarian cancer is a family history of breast or ovarian cancer, and approximately 25% of all ovarian cancers are caused by a heritable genetic condition. In about 65% of these cases, the genetic abnormality is a germline pathogenic variant in BRCA1/2 genes. Nevertheless, several other suppressor genes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome (MLH1, MSH2, PMS2, MLH6, and EPCAM), PALB2, BRIP1, RAD51C and RAD51D. Many clinical practices guidelines recommend that all women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes.
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Uterine corpus cancer is the sixth most commonly diagnosed cancer in women. Over 90% of uterine cancers are endometrial. Hereditary endometrial cancer makes up approximately 2% to 5% of all cases. Inherited mutations in MMR genes diagnostic for Lynch syndrome and PTEN diagnostic for Cowden syndrome are the most common inherited syndromes known to increase a woman’s lifetime risk of endometrial cancer.
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The role of germline testing for breast, ovarian or endometrial cancer has increased, with growing precision treatment implications and gene-specific management recommendations for carriers of germline variants related to increased risk of cancer.
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As many of the oncologists are used to group and study the different cancer types in systems or specialities, the main objective of this product is to provide them with a more manageable diagnostic tool according to their field of knowledge.
Indication
The Igenomix Women’s Cancer Precision Panel is indicated in those cases where the physician is suspecting of a hereditary cancer syndrome. It is designed to diagnose adults with a personal or family history suggestive of inherited breast, ovarian or endometrial cancer, providing important information that may impact cancer treatment as well as cancer risk assessment and management.
Clinical Utility
- Identify pathogenic cancer susceptibility variants
- Maximize surveillance and preventive strategies for at risk individuals
- Provide options and strategies for targeted treatment, therapeutic planning, and clinical trials
- Perform risk assessment and genetic counselling for family members (cascade testing)
References
LaDuca et al. A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients. Genet Med 22, 407–415 (2020). https://doi.org/10.1038/s41436-019-0633-8
Breast Cancer Association Consortium, Dorling L, et al. Breast Cancer Risk Genes – Association Analysis in More than 113,000 Women. N Engl J Med. 2021 Jan 20. doi: 10.1056/NEJMoa1913948. Epub ahead of print. PMID: 33471991.
Rahner, N., & Steinke, V. (2008). Hereditary cancer syndromes. Deutsches Arzteblatt international, 105(41), 706–714. https://doi.org/10.3238/arztebl.2008.0706
Syngal, S., Brand, R. E., Church, J. M., Giardiello, F. M., Hampel, H. L., Burt, R. W., & American College of Gastroenterology (2015). ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes. The American journal of gastroenterology, 110(2), 223–263. https://doi.org/10.1038/ajg.2014.435
Li et al. (2020). Points to consider for reporting of germline variation in patients undergoing tumor testing: a statement of the American College of Medical Genetics and Genomics (ACMG). Genetics In Medicine, 22(7), 1142-1148. doi: 10.1038/s41436-020-0783-8
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Fortner, R. T., Rice, M. S., Knutsen, S. F., Orlich, M. J., Visvanathan, K., Patel, A. V., Gaudet, M. M., Tjønneland, A., Kvaskoff, M., Kaaks, R., Trichopolou, A., Pala, V., Onland-Moret, N. C., Gram, I. T., Amiano, P., Idahl, A., Allen, N. E., Weiderpass, E., Poynter, J. N., Robien, K., … Schouten, L. J. (2020). Ovarian Cancer Risk Factor Associations by Primary Anatomic Site: The Ovarian Cancer Cohort Consortium. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 29(10), 2010–2018. https://doi.org/10.1158/1055-9965.EPI-20-0354
Alkabban, F. M., & Ferguson, T. (2021). Breast Cancer. In StatPearls. StatPearls Publishing.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. https://doi.org/10.3322/caac.21660
Understanding Inherited Risk in Unselected Newly Diagnosed Patients With Endometrial Cancer. DOI: 10.1200/PO.18.00338 JCO Precision Oncology – published online April 25, 2019
Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline. DOI https://doi.org/10.1200/JCO.19.02960
Epithelial ovarian câncer. Lancet 2019; 393: 1240–5
Risk-Reducing Bilateral Salpingo-Oophorectomy for Ovarian Cancer: A Review and Clinical Guide for Hereditary Predisposition Genes. DOI: 10.1200/OP.21.00382 JCO Oncology Practice 18, no. 3 (March 01, 2022) 201-209.