homologous recombination: the exchange of corresponding stretches of DNA between two sister chromosomes.
abstract (see abstract for stats)
PURPOSE:
To
investigate the impact of somatic mutations in homologous recombination
(HR) genes on the chemotherapeutic response and survival of patients
with epithelial ovarian cancer (EOC).
EXPERIMENTAL DESIGN:
We
performed targeted massively parallel sequencing of tumor DNA from 158
patients with EOC. We associated adjuvant chemotherapy and clinical
outcome with mutations in selected genes, focusing on those encoding HR
proteins.
RESULTS:
HR
mutations were found in 47 (30%) tumors. We did not detect an overall
survival (OS) difference in advanced stage patients whose tumors had HR
mutations compared to those without (median OS of 49.6 months) vs. 43.3 months. However, when
stratified by chemotherapy regimen, patients whose tumors had TP53 and
HR mutations demonstrated a marked survival advantage when treated with
platinum and paclitaxel vs. platinum +/- cyclophosphamide (median OS of
90 months vs. 29.5 months.
CONCLUSIONS:
Previous
studies demonstrating a survival advantage for EOC patients with
somatic HR mutations have been conducted with almost universal use of
both platinum and paclitaxel. Our study is the first to our knowledge to
compare cohorts with somatic HR gene mutations treated with and without
paclitaxel containing platinum regimens. The survival benefit
attributed to the platinum sensitivity of HR deficient ovarian cancers
may depend upon the combined use of paclitaxel.
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