TY - JOUR
T1 - Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer
T2 - an extension of the ovarian BRCAness phenotype
AU - Gourley, Charlie
AU - Michie, Caroline O.
AU - Roxburgh, Patricia
AU - Yap, Timothy A.
AU - Harden, Sharon
AU - Paul, Jim
AU - Ragupathy, Kalpana
AU - Todd, Radha
AU - Petty, Russell
AU - Reed, Nick
AU - Hayward, Richard L.
AU - Mitchell, Paul
AU - Rye, Tzyvia
AU - Schellens, Jan H. M.
AU - Lubinski, Jan
AU - Carmichael, James
AU - Kaye, Stan B.
AU - Mackean, Melanie
AU - Ferguson, Michelle
PY - 2010/5/20
Y1 - 2010/5/20
N2 - 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.
AB - 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.
KW - Adrenal Gland Neoplasms
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Brain Neoplasms
KW - Female
KW - Genes, BRCA1
KW - Genes, BRCA2
KW - Genetic Predisposition to Disease
KW - Germ-Line Mutation
KW - Humans
KW - Incidence
KW - Liver Neoplasms
KW - Lung Neoplasms
KW - Middle Aged
KW - Neoplasm Metastasis
KW - Ovarian Neoplasms
KW - Pancreatic Neoplasms
KW - Phenotype
KW - Scotland
KW - Splenic Neoplasms
U2 - 10.1200/JCO.2009.25.1082
DO - 10.1200/JCO.2009.25.1082
M3 - Article
C2 - 20406939
SN - 0732-183X
VL - 28
SP - 2505
EP - 2511
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -
