# Prevalence of Homologous Recombination Repair Mutations and Association with Clinical Outcomes in Patients with Solid Tumors: A Study Using the AACR Project GENIE Dataset

## TL;DR

This study found that mutations in DNA repair genes like BRCA are present in some cancer patients and may be linked to longer survival after standard treatments.

## Contribution

The study provides real-world data on the prevalence and survival outcomes of BRCA and HRR mutations in multiple cancer types.

## Key findings

- 3.4% of patients had BRCA gene mutations, and 8.7% had mutations in HRR genes.
- Patients with these mutations showed a trend toward longer survival after second-line cancer treatments.
- The association between mutations and survival was not strong when using PARP inhibitors or immunotherapy.

## Abstract

This study looked at mutations in BRCA genes and others referred to as homologous recombination repair (HRR) genes. Mutations in these genes are linked to problems in the DNA repair process, which can lead to cancer. Data from patients in a real-world setting were used to see how often these mutations occur and how they affect survival rates. We found that 3.4% of patients with cancer had tumors with mutations in BRCA genes, and 8.7% had tumors with mutations in HRR genes. We also found that among patients who had received at least two lines of standard treatment for advanced cancer, there was a trend toward longer survival in patients with these mutations compared to those without. This information is important for understanding the role of these genetic changes in different cancers and improving cancer treatment.

Background/Objectives: Mutations in BRCA1 and/or BRCA2 (BRCAm) and other homologous recombination repair genes (HRRm) are associated with several cancers. We evaluated the prevalence and association with overall survival (OS) of somatic BRCAm and HRRm among patients with advanced solid tumors. Methods: We used deidentified data from the AACR GENIE Biopharma Collaborative dataset derived from patients with tumors genotyped using next-generation sequencing between 1 January 2014 and 31 December 2017. Eligible patients were aged ≥18 years diagnosed with non-small-cell lung, colorectal, breast, bladder, prostate, or pancreatic cancer, with documented BRCA/HRR somatic mutation status. The primary analysis was OS (censored at the start of poly[ADP ribose] polymerase inhibitors [PARPi]/immunotherapy) after initiation of second-line therapy since most patients had sequencing after first-line therapy. Results: Among eligible patients, 242/7022 (3.4%) had BRCAm and 477/5474 (8.7%) had HRRm. Adjusted OS HRs (95% CI) for the primary analysis (using the initiation of second-line therapy as index date) were 0.79 (0.61–1.03) with/without BRCAm (n = 116/n = 3394) and 0.83 (0.69–0.99) with/without HRRm (n = 247/n = 2656); in sensitivity analysis of patients with stage IV disease, HRs were 0.97 (0.68–1.38) with/without BRCAm (n = 58/n = 1847) and 0.92 (0.73–1.18) with/without HRRm (n = 132/n = 1488). Conclusions: Overall, BRCAm and HRRm did not show a strong association with OS, with a trend toward longer OS among patients receiving standard second-line therapies excluding PARPi/immunotherapy.