Hereditary Ovarian Cancer: Towards a Cost-Effective Prevention Strategy

Abstract

Ovarian cancer (OC) is the most lethal gynaecological malignancy. The search for a widely affordable and accessible screening strategy to reduce mortality from OC is still ongoing. This coupled with the late-stage presentation and poor prognosis harbours significant health-economic implications. OC is also the most heritable of all cancers, with an estimated 25% of cases having a hereditary predisposition. Advancements in technology have detected multiple mutations, with the majority affecting the BRCA1 and/or BRCA2 genes. Women with BRCA mutations are at a significantly increased lifetime risk of developing OC, often presenting with a high-grade serous pathology, which is associated with higher mortality due to its aggressive characteristic. Therefore, a targeted, cost-effective approach to prevention is paramount to improve clinical outcomes and mortality. Current guidelines offer multiple preventive strategies for individuals with hereditary OC (HOC), including genetic counselling to identify the high-risk women and risk-reducing interventions (RRI), such as surgical management or chemoprophylaxis through contraceptive medications. Evidence for sporadic OC is abundant as compared to the existing dearth in the hereditary subgroup. Hence, our review article narrates an overview of HOC and explores the RRI developed over the years. It attempts to compare the cost effectiveness of these strategies with women of the general population in order to answer the crucial question: what is the most prudent clinically and economically effective strategy for prevention amongst high-risk women?

Keywords: BRCA; cost effectiveness; genetic testing; guidelines; ovarian cancer; risk-reducing surgery.

Figure 1

The illustration shows distribution of gene mutations in ovarian cancer. (a) Proportion of sporadic (75%) and hereditary (25%) ovarian cancer cases. (b) Details of HOC. The inner circle shows the proportions contributed by HBOC and Lynch Syndrome. The outer circle demonstrates the divisions shared by prominent genetic mutations (BRCA1, BRCA2, TP53) and mutation groups (mismatch repair genes, double-strand-break repair genes) corresponding approximately to the syndromic association in the inner circle.