<abstract xmlns="http://www.w3.org/1999/xhtml">The most frequently identified genetic cause of breast cancer is the germline mutation of <italic>BRCA1</italic> and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative.The most effective risk reduction strategy involves bilateral prophylactic mastectomy and bilateral salpingo-oophorectomy, eliminating 90% of breast and 97% of ovarian cancer risks, respectively. Before and until such surgery, surveillance with physical examination, mammography and magnetic resonance mammography, starting at 25–30 years of age, are recommended for the early diagnosis of breast cancer; semi-annual surveillance with physical examination, transvaginal ultrasound and serum CA-125 is recommended for women who have not had prophylactic surgery. Carriers diagnosed with breast cancer run a high risk for a new breast primary and this information should be used accordingly. PARP inhibitors is a new class of antineoplastic agents, already approved for advanced <italic>BRCA1/2</italic> mutant (germline or somatic) ovarian cancer.Multigene panel testing may follow a negative <italic>BRCA</italic> genetic test, often identifying other genetic causes of cancer, expanding its role in oncology. Further adoption of PARP inhibitors, refinement in estimation of BRCA-associated cancer risks and wider population testing, through NGS technology, may become available in the near future.</abstract>

The most frequently identified genetic cause of breast cancer is the germline mutation of BRCA1 and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative.The most effective risk reduction strategy involves bilateral prophylactic mastectomy and bilateral salpingo-oophorectomy, eliminating 90% of breast and 97% of ovarian cancer risks, respectively. Before and until such surgery, surveillance with physical examination, mammography and magnetic resonance mammography, starting at 25–30 years of age, are recommended for the early diagnosis of breast cancer; semi-annual surveillance with physical examination, transvaginal ultrasound and serum CA-125 is recommended for women who have not had prophylactic surgery. Carriers diagnosed with breast cancer run a high risk for a new breast primary and this information should be used accordingly. PARP inhibitors is a new class of antineoplastic agents, already approved for advanced BRCA1/2 mutant (germline or somatic) ovarian cancer.Multigene panel testing may follow a negative BRCA genetic test, often identifying other genetic causes of cancer, expanding its role in oncology. Further adoption of PARP inhibitors, refinement in estimation of BRCA-associated cancer risks and wider population testing, through NGS technology, may become available in the near future.

BRCA1/2 associated cancer susceptibility: a clinical overview

1st Department of Medical Oncology, Hygeia Hospital, Erythrou Stavrou 4, 15123 Marousi, Athens,

Forum of Clinical Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

{"article-title":"BRCA1/2 associated cancer susceptibility: a clinical overview"}

The most frequently identified genetic cause of breast cancer is the germline mutation of BRCA1 and 2 genes. The carriers of these mutations are at high risk...

BRCA1/2 associated cancer susceptibility: a clinical overview

Publicado en línea: 30 dic 2016

Páginas: 16 - 24

Recibido: 21 sept 2015

Aceptado: 05 feb 2016

DOI: https://doi.org/10.1515/fco-2015-0022

Palabras clave
Brca1, Brca2, Cancer susceptibility, Cancer genetics, Ovarian cancer, Breast cancer, Genetic counseling, Hereditary cancer, Parp inhibitors, Prophylactic surgery, Surveillance

© 2016 De Gruyter Open

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

BRCA1/2 associated cancer susceptibility: a clinical overview

Publicado en línea: 30 dic 2016

Páginas: 16 - 24

Recibido: 21 sept 2015

Aceptado: 05 feb 2016

DOI: https://doi.org/10.1515/fco-2015-0022

Palabras claveBrca1, Brca2, Cancer susceptibility, Cancer genetics, Ovarian cancer, Breast cancer, Genetic counseling, Hereditary cancer, Parp inhibitors, Prophylactic surgery, Surveillance

© 2016 De Gruyter Open

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Palabras clave
Brca1, Brca2, Cancer susceptibility, Cancer genetics, Ovarian cancer, Breast cancer, Genetic counseling, Hereditary cancer, Parp inhibitors, Prophylactic surgery, Surveillance