Abstract
We report an interesting clinical case of a patient carrying a specific BRCA2 germline variant affected by bone and hepatic metastases from a high grade uterine stromal sarcoma who obtained a complete metabolic response after only 3 cycles of trabectedin treatment (1.5 mg/m2 given intravenously over 24 hours every 21 days). Molecular investigations linked this outstanding positive pharmacological response with the loss of heterozygosity (LOH) of the mutated BRCA2 gene. These data support the hypothesis that the response to trabectedin may be positively conditioned by the different DNA repair defects present in the neoplasm and that BRCAness tumor genotype is important in determining the efficacy of trabectedin-based chemotherapy.
Keywords:
BRCA2 germline variant; DNA damage; mutations; soft tissue sarcoma; trabectedin; tumor genotype.
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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BRCA2 Protein / genetics*
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Base Sequence
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Bone Neoplasms / diagnostic imaging
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Bone Neoplasms / drug therapy
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Bone Neoplasms / genetics
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Bone Neoplasms / secondary
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Dioxoles / administration & dosage
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Endometrial Neoplasms / diagnostic imaging
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Endometrial Neoplasms / drug therapy*
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Endometrial Neoplasms / genetics*
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Endometrial Neoplasms / pathology
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Epirubicin / administration & dosage
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Female
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Genes, BRCA2
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Germ-Line Mutation
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Humans
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Ifosfamide / administration & dosage
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Liver Neoplasms / diagnostic imaging
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Liver Neoplasms / drug therapy
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Liver Neoplasms / genetics
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Liver Neoplasms / secondary
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Middle Aged
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Mutation, Missense*
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Sarcoma, Endometrial Stromal / diagnostic imaging
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Sarcoma, Endometrial Stromal / drug therapy*
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Sarcoma, Endometrial Stromal / genetics*
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Sarcoma, Endometrial Stromal / pathology
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Tetrahydroisoquinolines / administration & dosage
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Trabectedin
Substances
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BRCA2 Protein
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BRCA2 protein, human
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Dioxoles
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Tetrahydroisoquinolines
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Epirubicin
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Trabectedin
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Ifosfamide