Table 2 Summary of data to support investigation of candidate biomarkers

BRCA1 methylation

Multiple independent reports in ovarian cancer suggesting (i) mutual exclusivity with BRCA1 mutations (ii) coincidence with BRCA1 loss of heterozygosity. However, no reported BRCAm-like link to good prognosis and platinum sensitivity

^{37, 38}

BRCA1 protein

Low protein levels linked to increased duration of survival in platinum-treated ovarian cancer. However, some difficulties in reproducing data

^{39– 41}

HRR gene mutations

Preclinically linked to PARP inhibitor sensitivity. Mechanistically analogous to BRCAm and linked to prolonged survival and platinum sensitivity in ovarian cancer.

However, difficult to gauge impact of individual genes due to low prevalence and some evidence of non-mutual exclusivity

^{5, 8}

HRD score

Sensitive for BRCAm and BRCA1 methylation, relatively conserved between primary and metastatic lesions. Prognostic for and linked to higher platinum response rate. Evidence from ovarian cancer trials: shorter progression-free survival in patients with HRD-positive tumours without BRCA mutations vs those with BRCA mutations. Longer progression-free survival in patients with HRD-positive vs HRD-negative tumours; however, may serve as a genomic scar that is irreversible and unreflective of current tumour phenotype and, unlike BRCAm, was not predictive for platinum vs taxane in the TNT trial in breast cancer

^{11, 12, 17, 42, 43}