Comprehensive clinical cancer analysis of homologous recombination deficiency biomarkers in an academic…

Cohort studyNPJ precision oncology· Jul 2026

Comprehensive clinical cancer analysis of homologous recombination deficiency biomarkers in an academic molecular profiling program.

Heura Domènech, Sara Simonetti, Paula Romero-Lozano … Violeta Serra

Molecular Genetic PathologyCohort studyTreatmentQ1IF 9.6

BRCA1/BRCA2 reversion mutations after PARP inhibitor therapy linked to worse platinum response

Comprehensive clinical cancer analysis of homologous recombination deficiency biomarkers in an academic molecular profiling program.

Heura Domènech … Violeta Serra

NPJ precision oncology · Jul 2026

Background

PARP inhibitors (PARPi) are effective in tumors with homologous recombination repair (homologous recombination repair) deficiency (HRD), typically identified by germline/tumor mutations.

Methods

We evaluated strategies to improve detection and longitudinal monitoring of HRD across >500 tumor samples and >20 paired liquid biopsies, integrating genetic, genomic, and functional readouts.

n = >500 tumor samples

Results

>30%

Over 30% of tumors had reversion mutations predicting poor response to later platinum chemotherapy

n = >500 tumor samples

More results

However, genetic testing may miss intrinsic PARPi sensitivity and resistance.

HRD was more frequent in high-grade ovarian cancer (HGOC; 52%) than in metastatic breast (mBC; 12%) or prostate cancer (mPC; 20%).

Assay concordance was low-to-moderate, underscoring complementarity.

“

Conclusion

These findings support the use of complementary HRD biomarkers in tissue and liquid biopsy to guide PARPi use and monitor response.

Comprehensive clinical cancer analysis of homologous recombination deficiency biomarkers in an academic molecular profiling program.

Comprehensive clinical cancer analysis of homologous recombination deficiency biomarkers in an academic molecular profiling program.

Related papers