recent key development is the detection of a clear efficacy
signal for olaparib in patients with sporadic high-grade serous
ovarian cancer with a RECIST-based ORR of 24%.20 The collective
incidence of somatic mutations and epigenetic loss of BRCA1/2 in
patients with high-grade serous ovarian cancer is reportedly as
high as 55%.21 Another series reported somatic BRCA1/2 mutations
in 44 (19%) of 235 unselected patients with ovarian cancer,
with somatic origin being demonstrated in 11 (23%) of 28 patients
for whom germline DNA samples were also available.22 These
results suggest that the potential scope of application for this class
of agents may be considerably broadened. In this context, predictive
biomarkers of clinical benefit are being developed, including
functional assessments of homologous recombination deficiency,19 as
well as BRCA1/2 promoter hypermethylation and array-based assays
that detect BRCAness.23,2