Therapeutic options for mucinous ovarian carcinoma

Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poo...

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Bibliographic Details
Published in:Gynecologic oncology 2020-03, Vol.156 (3), p.552-560
Main Authors: Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Amarasinghe, Kaushalya C., Ananda, Sumitra, Bowtell, David D.L., Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Fereday, Sian, Gilks, C. Blake, Gourley, Charlie, Hadley, Alison M., Hendley, Joy, Hunter, Sally M., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, Li, Jason, Lupat, Richard, McNally, Orla M., McAlpine, Jessica N., Pyman, Jan, Rowley, Simone M., Salazar, Carolina, Saunders, Hugo, Semple, Timothy, Stephens, Andrew N., Thio, Niko, Torres, Michelle C., Traficante, Nadia, Zethoven, Magnus, Antill, Yoland C., Campbell, Ian G., Scott, Clare L.
Format: Article
Language:English
Subjects:
Adenocarcinoma, Mucinous - genetics
Adenocarcinoma, Mucinous - metabolism
Adenocarcinoma, Mucinous - pathology
Adenocarcinoma, Mucinous - therapy
Aged
Cohort Studies
DNA Mismatch Repair
Female
Genomic
Homologous Recombination
Humans
Immunohistochemistry
Molecular targeted therapy
Mutation
Neoplasm Staging
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
Precision oncology
Receptor, ErbB-2 - genetics
Receptor, ErbB-3 - genetics
Sequencing
Therapy
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Summary:Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117–166). Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition. •MOC often carry genetic events indicating a targeted therapy and should be entered in basket trials of such agents.•A distinct subset of MOC are estrogen receptor positive (~11%), suggesting hormonal therapy as an option.•Mismatch repair deficiency is present in
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2019.12.015