- 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:
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
Not as well-studied
Precise lifetime risks and tumor spectrum not yet determined
Guidelines for screening and prevention are limited or not available
% GENE COVERAGE (20X)
Breast Cancer, Colorectal Cancer, Cowden Syndrome, Meningioma, Proteus Syndrome
6 of 6
Ataxia-Telangiectasia, Breast Cancer, Mantle Cell Lymphoma
1608 of 1632
Breast Cancer, Hereditary Breast And Ovarian Cancer Syndrome
195 of 195
Breast Cancer, Familial Breast-Ovarian Cancer, Familial Pancreatic Carcinoma, Fanconi Anemia Complementation Group S, Hereditary Breast And Ovarian Cancer Syndrome, Primary Peritoneal Carcinoma
2783 of 2894
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
3343 of 3451
Brain Glioma, Synchronous Bilateral Breast Carcinoma
NA of NA
Breast Cancer, Fanconi Anemia Complementation Group J, Hereditary Breast And Ovarian Cancer Syndrome
235 of 237
Blepharo-Cheilo-Odontic Syndrome, Breast Cancer, Cleft Lip/Palate, Endometrial Carcinoma, Gastric Cancer, Prostate Cancer
361 of 363
Breast Cancer, Hereditary Breast And Ovarian Cancer Syndrome, Li-Fraumeni Syndrome, Osteosarcoma, Prostate Cancer
307 of 310
Hereditary Nonpolyposis Colorectal Cancer Type 8, Congenital Diarrhea With Tufting Enteropathy, Lynch Syndrome
52 of 70
Ovarian Cancer, Breast Cancer, Fanconi Anemia Complementation Group A
NA of NA
Fanconi Anemia Complementation Group C
75 of 75
Fanconi Anemia, Male Infertility With Azoospermia Or Oligozoospermia Due To Single Gene Mutation, Premature Ovarian Failure; Spermatogenic Failure
59 of 61
Xeroderma Pigmentosum Complementation Group G
6 of 6
Familial Isolated Hyperparathyroidism, Insulinoma, Multiple Endocrine Neoplasia Type 1, Pituitary Gigantism, Prolactinoma
871 of 876
Hereditary Nonpolyposis Colorectal Cancer Type 2, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome
1079 of 1118
Ataxia-Telangiectasia-Like Disorder, Hereditary Breast And Ovarian Cancer Syndrome
NA of NA
Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome
1032 of 1057
Hereditary Nonpolyposis Colorectal Cancer Type 5, Endometrial Carcinoma, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome
613 of 641
Familial Adenomatous Polyposis, Gastric Cancer, MUTYH-Related Attenuated Familial Adenomatous Polyposis
183 of 183
Aplastic Anemia, Hereditary Breast And Ovarian Cancer Syndrome, Acute Lymphocytic Leukemia, Nijmegen Breakage Syndrome
200 of 200
17q11.2 Microduplication Syndrome, Hereditary Pheochromocytoma-Paraganglioma, Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1, Neurofibromatosis-Noonan Syndrome, Familial Spinal Neurofibromatosis Type I, Watson Syndrome
3082 of 3166
Breast Cancer, Familial Pancreatic Carcinoma, Fanconi Anemia Complementation Group N, Hereditary Breast And Ovarian Cancer Syndrome
601 of 617
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
54 of 58
Hereditary Nonpolyposis Colorectal Cancer Type 4, Lynch Syndrome, Mismatch Repair Cancer Syndrome
264 of 285
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
609 of 629
Hereditary Breast And Ovarian Cancer Syndrome, Nijmegen Breakage Syndrome-like Disorder
117 of 120
Familial Breast-Ovarian Cancer, Fanconi Anemia Complementation Group O, Hereditary Breast And Ovarian Cancer Syndrome
130 of 130
Hereditary Breast And Ovarian Cancer Syndrome
97 of 97
Inherited Cancer-Predisposing Syndrome
32 of 34
Infantile Liver Failure Syndrome
16 of 16
Pancreatic Cancer, Peutz-Jeghers Syndrome, Testicular tumor
456 of 470
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
557 of 563
Fanconi Anemia Complementation Group U, Male Infertility With Azoospermia Or Oligozoospermia Due To Single Gene Mutation
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
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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