Platinum Sensitivity in a BRCA1 Mutation Carrier with Advanced Breast Cancer
ABSTRACT Although BRCA1-associated breast carcinomas are frequently detected in nodal-negative stage, they typically present with an aggressive histopathological phenotype that is reflected by a poor prognosis and an increased risk for distant metastatic spread. Recent in vitro data suggest a high sensitivity of BRCA1-associated carcinomas to platinum-based chemotherapy and a lower sensitivity to anthracyclines and taxanes. This is explained by the key role of BRCA1 in DNA double-strand repair via homologous recombination, thereby leading to a higher sensitivity to DNA intercalating agents, such as platinum. Here we present the case of a woman suffering from BRCA1-associated metastatic breast carcinoma that was resistant to docetaxel, but responded strongly to cisplatin-containing chemotherapy. This supports the rationale of ongoing clinical studies.
Cancer genetics and cytogenetics 02/2010; 197(1):91-4. · 1.54 Impact Factor
Article: Drug therapy for hereditary cancers.[show abstract] [hide abstract]
ABSTRACT: Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR) of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose) polymerase (PARP). Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC). Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC) patients; studies involving non-selected (i.e., both sporadic and hereditary) CRC with high-level microsatellite instability (MSI-H) suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP). Hereditary medullary thyroid cancers (MTC) have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.Hereditary Cancer in Clinical Practice 08/2011; 9(1):5. · 1.68 Impact Factor