- Breast cancer is the most common malignancy among females and the second most common cause of death from a neoplastic disease affecting women. Up to 5%-10% of breast cancer cases are hereditary and are caused by pathogenic mutations in genes such as BRCA1 and BRCA2 as well as germline mutations in other high penetrant genes. Nonetheless, some of these genes have been associated with other cancers, such as ovarian, pancreatic and colorectal cancer.
- Hereditary cancer syndromes are encountered in all medical specialties. Although they account for about 5% of all malignancies, it is of special importance to identify these patients because, unlike patients with sporadic cancers, they require special, long-term care as their predisposition can cause them to develop certain tumors at a relatively early age. These cancers can arise in the lungs, kidneys, liver, pancreas, skin, eyes, heart. Most hereditary cancers are associated with a “germline mutation” that will be present in every cell of the human body. Identification of patients at risk of inherited cancer susceptibility is dependent upon the ability to characterize genes and alterations associated with increased cancer risk as well as gathering a detailed personal and family history aiding in the identification of the mode of inheritance as well as other family members at risk of suffering from this susceptibility. Most of these genes are inherited in an autosomal dominant fashion.
- The Igenomix Hereditary Breast Cancer Precision Panel can be used as a screening and diagnostic tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved, and their high or intermediate penetrance.
The Igenomix Hereditary Breast Cancer Precision Panel is indicated in those cases where there are:
- Individuals with personal history of breast/ovarian cancer and one of the following
- Breast and/or ovarian or pancreatic cancer in at least two blood relatives.
- Multiple primary breast cancers or bilateral breast cancer first diagnosed before the age of 50 years.
- Premenopausal triple negative breast cancer diagnosed at a young age (<45 years).
- Male breast cancer in a blood relative.
- Ethnicities with high BRCA mutation frequency, such as Ashkenazi Jews, should be tested, even in the absence of family history.
The clinical utility of this panel is:
- The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history suggestive of hereditary breast cancer.
- Early initiation of treatment with a multidisciplinary team for appropriate surveillance, chemoprevention and risk-reducing mastectomy (RRM) or risk-reduction salpingo-oophorectomy.
- Risk assessment of asymptomatic family members according to the mode of inheritance
- Reduce morbidity related to breast cancer or morbidity secondary to complications of surveillance and treatment.
- Improved pathways from diagnosis to treatment in susceptible populations.
Genes & Diseases
List of genes included in the Hereditary Breast Cancer Precision Panel.
Most relevant genes have been classified according to:
|High Risk||Well studied|
|Greater than 4-fold risk of developing one or more cancers|
|Can cause a moderate risk for other cancers|
|Guidelines or expert opinion for cancer screening and prevention|
|2- to 4-fold risk of developing one or more cancers|
|May increase risk for other cancers|
|Limited guidelines for screening and prevention|
|Research||Not as well-studied|
|Precise lifetime risks and tumor spectrum not yet determined|
|Guidelines for screening and prevention are limited or not available|
|GENE||RISK||OMIM DISEASES||INHERITANCE*||% GENE COVERAGE (20X)||HGMD**|
|AKT1||Breast Cancer, Colorectal Cancer, Cowden Syndrome, Meningioma, Proteus Syndrome||AD||100%||6 of 6|
|ATM||Moderate risk||Ataxia-Telangiectasia, Breast Cancer, Mantle Cell Lymphoma||AD,AR||99.93%||1608 of 1632|
|BARD1||Moderate risk||Breast Cancer, Hereditary Breast And Ovarian Cancer Syndrome||AD||99.86%||195 of 195|
|BRCA1||High risk||Breast Cancer, Familial Breast-Ovarian Cancer, Familial Pancreatic Carcinoma, Fanconi Anemia Complementation Group S, Hereditary Breast And Ovarian Cancer Syndrome, Primary Peritoneal Carcinoma||AD,AR,MU||98.97%||2783 of 2894|
|BRCA2||High risk||Breast Cancer, Familial Breast-Ovarian Cancer, Familial Pancreatic Carcinoma, Fanconi Anemia Complementation Group D1, Glioma, Hereditary Breast And Ovarian Cancer Syndrome, Medulloblastoma, Nephroblastoma, Pancreatic Cancer, Prostate Cancer, Wilms Tumor||AD,AR,MU||98.51%||3343 of 3451|
|BRE||Brain Glioma, Synchronous Bilateral Breast Carcinoma||98.20%||NA of NA|
|BRIP1||Moderate risk||Breast Cancer, Fanconi Anemia Complementation Group J, Hereditary Breast And Ovarian Cancer Syndrome||AD,AR||94.97%||235 of 237|
|CDH1||High risk||Blepharo-Cheilo-Odontic Syndrome, Breast Cancer, Cleft Lip/Palate, Endometrial Carcinoma, Gastric Cancer, Prostate Cancer||AD||100%||361 of 363|
|CHEK2||Moderate risk||Breast Cancer, Hereditary Breast And Ovarian Cancer Syndrome, Li-Fraumeni Syndrome, Osteosarcoma, Prostate Cancer||AD||99.47%||307 of 310|
|EPCAM||Hereditary Nonpolyposis Colorectal Cancer Type 8, Congenital Diarrhea With Tufting Enteropathy, Lynch Syndrome||AR||99.94%||52 of 70|
|FAM175A||Moderate risk||Ovarian Cancer, Breast Cancer, Fanconi Anemia Complementation Group A||–||94.81%||NA of NA|
|FANCC||Fanconi Anemia Complementation Group C||AR||100%||75 of 75|
|FANCM||Fanconi Anemia, Male Infertility With Azoospermia Or Oligozoospermia Due To Single Gene Mutation, Premature Ovarian Failure; Spermatogenic Failure||AR||99.73%||59 of 61|
|GEN1||Xeroderma Pigmentosum Complementation Group G||–||99.71%||6 of 6|
|MEN1||Familial Isolated Hyperparathyroidism, Insulinoma, Multiple Endocrine Neoplasia Type 1, Pituitary Gigantism, Prolactinoma||AD||99.90%||871 of 876|
|MLH1||Hereditary Nonpolyposis Colorectal Cancer Type 2, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome||AD,AR||99.94%||1079 of 1118|
|MRE11||Moderate risk||Ataxia-Telangiectasia-Like Disorder, Hereditary Breast And Ovarian Cancer Syndrome||AR||99.95%||NA of NA|
|MSH2||Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome||AD,AR||99.99%||1032 of 1057|
|MSH6||Hereditary Nonpolyposis Colorectal Cancer Type 5, Endometrial Carcinoma, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome||AD,AR||99.28%||613 of 641|
|MUTYH||Familial Adenomatous Polyposis, Gastric Cancer, MUTYH-Related Attenuated Familial Adenomatous Polyposis||AR||100%||183 of 183|
|NBN||Moderate risk||Aplastic Anemia, Hereditary Breast And Ovarian Cancer Syndrome, Acute Lymphocytic Leukemia, Nijmegen Breakage Syndrome||AR,MU,P||100%||200 of 200|
|NF1||17q11.2 Microduplication Syndrome, Hereditary Pheochromocytoma-Paraganglioma, Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1, Neurofibromatosis-Noonan Syndrome, Familial Spinal Neurofibromatosis Type I, Watson Syndrome||AD||97.97%||3082 of 3166|
|PALB2||Breast Cancer, Familial Pancreatic Carcinoma, Fanconi Anemia Complementation Group N, Hereditary Breast And Ovarian Cancer Syndrome||AD,AR||98.78%||601 of 617|
|PIK3CA||Breast Cancer, Capillary Malformation Of The Lower Lip, Lymphatic Malformation Of Face And Neck, Asymmetry Of Face And Limbs And Partial/Generalized Overgrowth, Colorectal Cancer, Congenital Lipomatous Overgrowth, Vascular Malformations And Epidermal Nevi, Cowden Syndrome, Gastric Cancer, Hemihyperplasia-Multiple Lipomatosis Syndrome, Hepatocellular Carcinoma, Seborrheic Keratosis, Lung Cancer, Lynch Syndrome, Macrocephaly-Capillary Malformation, Meningioma||AD||99.58%||54 of 58|
|PMS2||Hereditary Nonpolyposis Colorectal Cancer Type 4, Lynch Syndrome, Mismatch Repair Cancer Syndrome||AD,AR||97.17%||264 of 285|
|PTEN||High risk||Bannayan-Riley-Ruvalcaba Syndrome, Cowden Disease, Hereditary Breast And Ovarian Cancer Syndrome, Juvenile Polyposis Of Infancy, Lhermitte-Duclos Disease, Macrocephaly/Autism Syndrome, Familial Meningioma, Prostate Cancer, Proteus Syndrome, Proteus-Like Syndrome, Segmental Outgrowth-Lipomatosis-Arteriovenous Malformation-Epidermal Nevus Syndrome||AD||99.97%||609 of 629|
|RAD50||Moderate risk||Hereditary Breast And Ovarian Cancer Syndrome, Nijmegen Breakage Syndrome-like Disorder||AR||99.94%||117 of 120|
|RAD51C||Moderate risk||Familial Breast-Ovarian Cancer, Fanconi Anemia Complementation Group O, Hereditary Breast And Ovarian Cancer Syndrome||AR||100%||130 of 130|
|RAD51D||Moderate risk||Hereditary Breast And Ovarian Cancer Syndrome||–||100%||97 of 97|
|RECQL||Inherited Cancer-Predisposing Syndrome||–||99.71%||32 of 34|
|RINT1||Infantile Liver Failure Syndrome||AR||99.96%||16 of 16|
|STK11||High risk||Pancreatic Cancer, Peutz-Jeghers Syndrome, Testicular tumor||AD||81.99%||456 of 470|
|TP53||High risk||Adrenocortical Carcinoma, Basal Cell Carcinoma, Bone Marrow Failure Syndrome, Breast Cancer, Colorectal Cancer, Essential Thrombocythemia, Familial Pancreatic Carcinoma, Glioma, Hepatocellular Carcinoma, Hereditary Breast And Ovarian Cancer Syndrome, Li-Fraumeni Syndrome, Nasopharyngeal Carcinoma, Osteosarcoma, Pancreatic Cancer, Papilloma Of Choroid Plexus||AD,MU,P||98.92%||557 of 563|
Fanconi Anemia Complementation Group U, Male Infertility With Azoospermia Or Oligozoospermia Due To Single Gene Mutation
|AR||98.39%||28 of 28|
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
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Yamauchi, H., & Takei, J. (2018). Management of hereditary breast and ovarian cancer. International journal of clinical oncology, 23(1), 45–51. https://doi.org/10.1007/s10147-017-1208-9
Apostolou, P., & Fostira, F. (2013). Hereditary breast cancer: the era of new susceptibility genes. BioMed research international, 2013, 747318. https://doi.org/10.1155/2013/747318
National Comprehensive Cancer Network. (2021). Retrieved from https://www.nccn.org/professionals/physician_gls/default.aspx#detection
Hereditary Breast and Ovarian Cancer. (2021). Retrieved 16 February 2021, from https://www.cancer.net/cancer-types/hereditary-breast-and-ovarian-cancer
Cao, A., Huang, L., & Shao, Z. (2017). The Preventive Intervention of Hereditary Breast Cancer. Advances in experimental medicine and biology, 1026, 41–57. https://doi.org/10.1007/978-981-10-6020-5_3