PURPOSE: We evaluated the clinical impact of germ-line BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to first and subsequent lines of chemotherapy, treatment-free interval (TFI) between each line of therapy, and overall survival (OS). PATIENTS AND METHODS: Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA-positive) were selected from our database and matched (1:2) with 44 nonhereditary EOC controls (defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. All patients received primary platinum-based chemotherapy. Statistical comparisons included responses after first-, second-, and third-line treatment (chi(2)/Fisher's exact test) and median OS (Kaplan-Meier method/log-rank test). RESULTS: Compared with controls, BRCA-positive patients had higher overall (95.5% v 59.1%; P = .002) and complete response rates (81.8% v 43.2%; P = .004) to first line treatment, higher responses to second and third line platinum-based chemotherapy (second line, 91.7% v 40.9% [P = .004]; third line, 100% v 14.3% [P = .005]) and longer TFIs. A significant improvement in median OS in BRCA-positive patients compared with controls was observed from both time of diagnosis (8.4 v 2.9 years; P < .002) and time of first relapse (5 v 1.6 years; P < .001). BRCA status, stage, and length of first response were independent prognostic factors from time of first relapse. CONCLUSION: BRCA-positive EOC patients have better outcomes than nonhereditary EOC patients. There exists a clinical syndrome of BRCAness that includes serous histology, high response rates to first and subsequent lines of platinum-based treatment, longer TFIs between relapses, and improved OS.
PURPOSE: We evaluated the clinical impact of germ-line BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to first and subsequent lines of chemotherapy, treatment-free interval (TFI) between each line of therapy, and overall survival (OS). PATIENTS AND METHODS: Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA-positive) were selected from our database and matched (1:2) with 44 nonhereditary EOC controls (defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. All patients received primary platinum-based chemotherapy. Statistical comparisons included responses after first-, second-, and third-line treatment (chi(2)/Fisher's exact test) and median OS (Kaplan-Meier method/log-rank test). RESULTS: Compared with controls, BRCA-positive patients had higher overall (95.5% v 59.1%; P = .002) and complete response rates (81.8% v 43.2%; P = .004) to first line treatment, higher responses to second and third line platinum-based chemotherapy (second line, 91.7% v 40.9% [P = .004]; third line, 100% v 14.3% [P = .005]) and longer TFIs. A significant improvement in median OS in BRCA-positive patients compared with controls was observed from both time of diagnosis (8.4 v 2.9 years; P < .002) and time of first relapse (5 v 1.6 years; P < .001). BRCA status, stage, and length of first response were independent prognostic factors from time of first relapse. CONCLUSION:BRCA-positive EOC patients have better outcomes than nonhereditary EOC patients. There exists a clinical syndrome of BRCAness that includes serous histology, high response rates to first and subsequent lines of platinum-based treatment, longer TFIs between relapses, and improved OS.
Authors: Kelly L Bolton; Georgia Chenevix-Trench; Cindy Goh; Siegal Sadetzki; Susan J Ramus; Beth Y Karlan; Diether Lambrechts; Evelyn Despierre; Daniel Barrowdale; Lesley McGuffog; Sue Healey; Douglas F Easton; Olga Sinilnikova; Javier Benítez; María J García; Susan Neuhausen; Mitchell H Gail; Patricia Hartge; Susan Peock; Debra Frost; D Gareth Evans; Rosalind Eeles; Andrew K Godwin; Mary B Daly; Ava Kwong; Edmond S K Ma; Conxi Lázaro; Ignacio Blanco; Marco Montagna; Emma D'Andrea; Maria Ornella Nicoletto; Sharon E Johnatty; Susanne Krüger Kjær; Allan Jensen; Estrid Høgdall; Ellen L Goode; Brooke L Fridley; Jennifer T Loud; Mark H Greene; Phuong L Mai; Angela Chetrit; Flora Lubin; Galit Hirsh-Yechezkel; Gord Glendon; Irene L Andrulis; Amanda E Toland; Leigha Senter; Martin E Gore; Charlie Gourley; Caroline O Michie; Honglin Song; Jonathan Tyrer; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Ulf Kristoffersson; Håkan Olsson; Åke Borg; Douglas A Levine; Linda Steele; Mary S Beattie; Salina Chan; Robert L Nussbaum; Kirsten B Moysich; Jenny Gross; Ilana Cass; Christine Walsh; Andrew J Li; Ronald Leuchter; Ora Gordon; Montserrat Garcia-Closas; Simon A Gayther; Stephen J Chanock; Antonis C Antoniou; Paul D P Pharoah Journal: JAMA Date: 2012-01-25 Impact factor: 56.272
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