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Enhanced response rate to pegylated liposomal doxorubicin in high grade serous ovarian carcinomas harbouring BRCA1 and BRCA2 aberrations.
- Source :
-
BMC cancer [BMC Cancer] 2018 Jan 03; Vol. 18 (1), pp. 16. Date of Electronic Publication: 2018 Jan 03. - Publication Year :
- 2018
-
Abstract
- Background: Approximately 10-15% of ovarian carcinomas (OC) are attributed to inherited susceptibility, the majority of which are due to mutations in BRCA1 or BRCA2 (BRCA1/2). These patients display superior clinical outcome, including enhanced sensitivity to platinum-based chemotherapy. Here, we seek to investigate whether BRCA1/2 status influences the response rate to single-agent pegylated liposomal doxorubicin (PLD) in high grade serous (HGS) OC.<br />Methods: One hundred and forty-eight patients treated with single-agent PLD were identified retrospectively from the Edinburgh Ovarian Cancer Database. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) archival tumour material and sequenced using the Ion Ampliseq BRCA1 and BRCA2 panel. A minimum variant allele frequency threshold was applied to correct for sequencing artefacts associated with formalin fixation.<br />Results: A superior response rate to PLD was observed in patients with HGS OC who harboured variants likely to affect BRCA1 or BRCA2 function compared to the BRCA1/2 wild-type population (36%, 9 of 25 patients versus 12.1%, 7 of 58 patients; p = 0.016). An enhanced response rate was also seen in patients harbouring only the BRCA1 SNP rs1799950, predicted to be detrimental to BRCA1 function (50%, 3 of 6 patients versus 12.1%, 7 of 58 patients; p = 0.044).<br />Conclusions: These data demonstrate that HGS OC patients with BRCA1/2 variants predicted damaging to protein function experience superior sensitivity to PLD, consistent with impaired DNA repair. Further characterisation of rs1799950 is now warranted in relation to chemosensitivity and susceptibility to developing ovarian carcinoma.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor genetics
Cystadenocarcinoma, Serous genetics
Cystadenocarcinoma, Serous pathology
Doxorubicin therapeutic use
Female
Follow-Up Studies
Genetic Predisposition to Disease
Humans
Middle Aged
Neoplasm Grading
Ovarian Neoplasms genetics
Ovarian Neoplasms pathology
Polyethylene Glycols therapeutic use
Polymorphism, Single Nucleotide
Retrospective Studies
Survival Rate
Antibiotics, Antineoplastic therapeutic use
BRCA1 Protein genetics
BRCA2 Protein genetics
Cystadenocarcinoma, Serous drug therapy
Doxorubicin analogs & derivatives
Mutation
Ovarian Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29298688
- Full Text :
- https://doi.org/10.1186/s12885-017-3981-2