Introduction/Background BRCA mutations and HR deficient (HRD) status influences the magnitude of PARP-inhibitors (PARP-i) benefit over Progression Free Survival and therefore are important factors in ovarian cancer diagnosis and treatment decisions. In this review we offer an overview of the state of the art regarding the actual knowledge about BRCA and HRD mutational status, the rationale of PARP-i use and HRD testing (current and in development assays) and their implications in clinical pratice and in the treatment decision process.

Methodology Review of literature.

Results PARP-i show higher efficacy in BRCA mutated patients, but they are also effective, though to a lesser degree, in HRD patients, HR proficient (HRP) patients and patients with unknown mutational status. HRD testing is strongly recommended by the main guidelines, however current tests used in pivotal studies have some limitations. Firstly, they can’t reliably exclude all patients who don’t benefit from PARP-i maintenance, as shown by the fact that even some HRP patients respond to PARP-i. Therefore, it would be more correct to refer to ’patient with negative test’. Secondly, such tests are not sensitive to dynamic changes in tumor genetics, which throw reversion or secondary mutations of homologous recombination (HR) genes, they can restore an HRP status and cause chemio-resistance. Functional assays (i.e RAD51 foci quantification) hence are under development, providing a real time genomic status. Equally promising are clinical studies featuring organoids and xenograft models in order to perform functional HRD tests and to test a patient's sensitivity to available therapies. Creation of models that can predict chemiotherapy and PARP-i sensitivity and response, by integrating clinical, histological and molecular data, are under study.

Conclusion HR status has a prognostic and predictive value. The development of more accurate and precise genomic tests may allow to chose the best tailored therapy and change the history of ovarian cancer patients.

Disclosures None.