Hereditary Breast and Ovarian Cancer
Breast cancer is the most common malignancy among females and the second most common cause of death from a neoplastic disease affecting women.

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 and Ovarian 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 and Ovarian Cancer Precision Panel is indicated in those cases where there are:
The clinical utility of this panel is:
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 |
Moderate Risk |
Well-studied |
|
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 life timerisks 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, |
AD |
100% |
6 of 6 |
ATM |
Moderate risk |
Ataxia- |
AD,AR |
99.93% |
1608 of 1632 |
BARD1 |
Moderate risk |
Breast |
AD |
99.86% |
195 of 195 |
BRCA1 |
High risk |
Breast |
AD,AR,MU |
98.97% |
2783 of 2894 |
BRCA2 |
High risk |
Breast Cancer, |
AD,AR,MU |
98.51% |
3343 of 3451 |
BRE |
|
Brain Glioma, |
|
98.20% |
NA of NA |
BRIP1 |
Moderate risk |
Breast Cancer, |
AD,AR |
94.97% |
235 of 237 |
CDH1 |
High risk |
Blepharo- |
AD |
100% |
361 of 363 |
CHEK2 |
Moderate risk |
Breast Cancer, |
AD |
99.47% |
307 of 310 |
EPCAM |
|
Hereditary |
AR |
99.94% |
52 of 70 |
FAM175A |
Moderate risk |
Ovarian |
– |
94.81% |
NA of NA |
FANCC |
|
Fanconi |
AR |
100% |
75 of 75 |
FANCM |
|
Fanconi |
AR |
99.73% |
59 of 61 |
GEN1 |
|
Xeroderma |
– |
99.71% |
6 of 6 |
MEN1 |
|
Familial |
AD |
99.90% |
871 of 876 |
MLH1 |
|
Hereditary |
AD,AR |
99.94% |
1079 of 1118 |
MRE11 |
Moderate risk |
Ataxia- |
AR |
99.95% |
NA of NA |
MSH2 |
|
Lynch Syndrome, |
AD,AR |
99.99% |
1032 of 1057 |
MSH6 |
|
Hereditary |
AD,AR |
99.28% |
613 of 641 |
MUTYH |
|
Familial |
AR |
100% |
183 of 183 |
NBN |
Moderate risk |
Aplastic Anemia, |
AR,MU,P |
100% |
200 of 200 |
NF1 |
|
17q11.2 |
AD |
97.97% |
3082 of 3166 |
PALB2 |
|
Breast Cancer, |
AD,AR |
98.78% |
601 of 617 |
PIK3CA |
|
Breast Cancer, |
AD |
99.58% |
54 of 58 |
PMS2 |
|
Hereditary |
AD,AR |
97.17% |
264 of 285 |
PTEN |
High risk |
Bannayan-Riley- |
AD |
99.97% |
609 of 629 |
RAD50 |
Moderate risk |
Hereditary |
AR |
99.94% |
117 of 120 |
RAD51C |
Moderate risk |
Familial Breast- |
AR |
100% |
130 of 130 |
RAD51D |
Moderate risk |
Hereditary |
– |
100% |
97 of 97 |
RECQL |
|
Inherited |
– |
99.71% |
32 of 34 |
RINT1 |
|
Infantile |
AR |
99.96% |
16 of 16 |
STK11 |
High risk |
Pancreatic |
AD |
81.99% |
456 of 470 |
TP53 |
High risk |
Adrenocortical |
AD,MU,P |
98.92% |
557 of 563 |
XRCC2 |
|
Fanconi Anemia |
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
Paul, A., & Paul, S. (2014). The breast cancer susceptibility genes (BRCA) in breast and ovarian cancers. Frontiers in bioscience (Landmark edition), 19, 605–618. https://doi.org/10.2741/4230
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