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Increased Incidence of Visceral Metastases in Scottish Patients With BRCA1/2-Defective Ovarian Cancer: An Extension of the Ovarian BRCAness Phenotype

2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15 Linguagem: Inglês

10.1200/jco.2009.25.1082

1527-7755

Charlie Gourley, Caroline O. Michie, Patricia Roxburgh, Timothy A. Yap, Sharon Harden, James Paul, Kalpana Ragupathy, R Todd, Russell Petty, Nick Reed, Richard L. Hayward, Paul Mitchell, Tzyvia Rye, Jan H.M. Schellens, Jan Lubiński, James Carmichael, Stan B. Kaye, Melanie Mackean, Michelle Ferguson,

PARP inhibition in cancer therapy

Purpose To compare the frequency of visceral relapse of BRCA1/2-deficient ovarian cancer to that of nonhereditary controls. Patients and Methods All patients diagnosed in Scotland with epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and a germline BRCA1/2 mutation were identified. Those with previous malignancy were excluded. Each remaining patient who experienced relapse was matched with two nonhereditary controls. Results Seventy-nine patients with EOC/PPC and germline BRCA1/2 mutations were identified. Fifteen had inadequate clinical data, two had carcinosarcoma, 27 had previous breast cancer, and 16 were in remission. Of the remaining 19 patients who were BRCA1/2 deficient, 14 patients (74%) developed visceral metastases compared with six (16%) of 38 patients in the control group. The percentages of liver, lung, and splenic metastases were 53%, 32%, and 32%, respectively, in the patients compared with 5%, 3%, and 5%, respectively, in the controls. When events occurring outside the matched follow-up period were omitted, the percentages of visceral, liver, lung, and splenic metastases were 58%, 42%, 16%, and 32% in the patients compared with 5%, 0%, 0%, and 3% in controls (P < .001, P < .001, P = .066, and P = .011, respectively). In an independent validation set, the corresponding percentages of visceral, liver, lung, and splenic metastases were 63%, 46%, 13%, and 17% in the patients compared with 11%, 4%, 2%, and 2% in controls (P < .001, P < .001, P = .153, and P = .052, respectively). Conclusion Although sporadic EOC commonly remains confined to the peritoneum, BRCA1/2-deficient ovarian cancer frequently metastasizes to viscera. These data extend the ovarian BRCAness phenotype, imply BRCA1/2-deficient ovarian cancer is biologically distinct, and suggest that patients with visceral metastases should be considered for BRCA1/2 sequencing.