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ESMO V-Learning: BRCA Across Tumour Types

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Learning objectives

  1. To understand the implications of germline BRCA testing in terms of cancer risk assessment  
  2. To understand the implications of germline BRCA testing from the perspective of early cancer detection and prevention
  3. To understand the implications of germline BRCA testing as a predictive biomarker for targeted therapies

Description

This module provides a comprehensive learning material in terms of BRCA1 and BRCA2 genes; role of BRCA1 and BRCA2 proteins, epidemiology of germline BRCA mutations across different tumour types, clinical predictors and cancer risk assessment of germline BRCA mutations; prevention and surveillance in BRCA mutation carriers and family members, overview of targeted therapies in patients with breast, ovarian, pancreatic and prostate cancers with BRCA mutations; safety profile of PARP inhibitors, as well as current understanding of BRCA deficiency and immune activation/suppression.

BRCA1 is a pleiotropic DNA damage repair protein that functions in both checkpoint activation and DNA repair. BRCA1 is a versatile protein that links DNA damage sensing and DNA damage repair effectors. BRCA2 is a mediator of the core mechanism of homologous recombination repair. Their inactivation leads to carcinogenesis.

In this module, the author elaborates the germline testing of BRCA1/2 genes regarding its multiple implications: cancer risk assessment, surveillance/cancer prevention, use of targeted therapy.

Individuals with a germline BRCA1/2 mutation have an increased risk of breast cancer, ovarian cancer, pancreatic cancer, male breast cancer, prostate cancer.

Surveillance recommendations and risk reduction surgeries are individualised in individuals with a germline BRCA1/2 mutation.

BRCA1/2 mutations may cause homologous recombination deficiency and be a predictive biomarker for targeted therapies, i.e. platinums and PARP inhibitors. Several PARP inhibitors have been approved by regulatory agencies for ovarian, breast, or prostate cancer (breakthrough designation) with a germline or somatic BRCA mutation.

Mainstream genetic testing for therapeutic indications will likely increase the number of mutation carriers identified and it will be an opportunity for cascade testing in relatives who may benefit from individualised surveillance and
prevention options.

This module represents ESMO commitment to contextualize the current evidence and provide future perspective in terms of biomarkers across different tumour types.

Declaration of interest

Judith Balmaña has reported:
Member of the speakers’ bureau of Astra Zeneca. Advisory role for Pfizer, Clovis, and Tesaro.

Last update: 21 Jun 2018

This E-Learning module was published in 2018. The CME test expired in 2020.

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