ESMO E-Learning: Management of BRCA Mutated Ovarian Cancer

Learning Objectives

  • To learn about the role of BRCA Mutations and DNA repair defects in ovarian cancer
  • To provide an update on clinical activity and indications for use of PARP inhibitors in ovarian cancer
  • To learn about future strategies in the development of PARP inhibitors
Title Duration Content CME Points CME Test
Management of BRCA Mutated Ovarian Cancer 46 min. 54 slides 1 Take Test
Jonathan Ledermann
Jonathan Ledermann
Read more

Germline mutations of BRCA1 or BRCA2 cancer susceptibility genes, are inherited as an autosomal dominant gene. The life time risk of ovarian cancer, taking BRCA 1 and 2 mutations together, is in the region of 40/60%. Although the mechanism of cancer development is not fully understood deletion of normal allele leads to cancer susceptibility through loss of function of homologous DNA repair, genomic stability, translational regulation, protein ubiquitination, chromatin remodelling and Cell cycle control. A mutation is found in approximately 1 in 400 of the population but it is much higher in certain ethnic groups.

Epidemiological data estimate that a germline BRCA mutation is found in about 17% of women with high grade ovarian/fallopian tube/ peritoneal cancers. Counselling and testing pathways vary throughout Europe. Historically referrals were made to cancer geneticists and the focus has been on identifying unaffected relatives, and not for treatment decisions.

However, in this module, the author tries to convey a message that testing should no longer be dependent on family history and that new referral pathways are needed. Training of gynaecologists and oncologists in providing information and obtaining consent for germline BRCA testing is needed. Testing tumours for both somatic and germline mutations should be considered, as 6-8% of patients have somatic BRCA mutation.

This module outlines chapters on BRCA mutated ovarian cancer, epidemiology, PARP inhibitors in BRCA mutated ovarian cancer, clinical activity of PARP inhibitors in ovarian cancer, PARP inhibitors beyond BRCA mutated ovarian cancer, indications for use of PARP inhibitors in ovarian cancer, and future strategies for the development of PARP inhibitors.

In a part of the module on development strategies for PARP inhibitors in ovarian cancer, the author elaborates a comparison of PARP inhibitors with chemotherapy, questions if PARP inhibitors will have additive effects to chemotherapy, and provides evidence for maintenance therapy with PARP inhibitors.

The author further discusses PARP inhibitors for routine care of BRCA mutated ovarian cancer, side effects of PARP inhibitors, quality of life issues, landscape of PARP inhibitors in clinical development, patient selection for treatment with PARP inhibitors, and future directions.

Last update: 12 August 2015

The author has reported to be: Chief Investigator for Study 19 Olaparib; Co-Chief Investigator ARIEL 3 Rucaparib Trial. He has participated in the Advisory Boards of AstraZeneca and Clovis, without personal remuneration.