Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer

an extension of the ovarian BRCAness phenotype

Charlie Gourley (Lead / Corresponding author), Caroline O. Michie, Patricia Roxburgh, Timothy A. Yap, Sharon Harden, Jim Paul, Kalpana Ragupathy, Radha Todd, Russell Petty, Nick Reed, Richard L. Hayward, Paul Mitchell, Tzyvia Rye, Jan H. M. Schellens, Jan Lubinski, James Carmichael, Stan B. Kaye, Melanie Mackean, Michelle Ferguson

    Research output: Contribution to journalArticle

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2505-2511
    Number of pages7
    JournalJournal of Clinical Oncology
    Volume28
    Issue number15
    DOIs
    Publication statusPublished - 20 May 2010

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    Ovarian Neoplasms
    Neoplasm Metastasis
    Phenotype
    Incidence
    Lung
    Liver
    Carcinosarcoma
    Recurrence
    Neoplasms
    Mutation
    Viscera
    Peritoneum
    Scotland
    Breast Neoplasms
    Control Groups

    Keywords

    • Adrenal Gland Neoplasms
    • Adult
    • Aged
    • Aged, 80 and over
    • Brain Neoplasms
    • Female
    • Genes, BRCA1
    • Genes, BRCA2
    • Genetic Predisposition to Disease
    • Germ-Line Mutation
    • Humans
    • Incidence
    • Liver Neoplasms
    • Lung Neoplasms
    • Middle Aged
    • Neoplasm Metastasis
    • Ovarian Neoplasms
    • Pancreatic Neoplasms
    • Phenotype
    • Scotland
    • Splenic Neoplasms

    Cite this

    Gourley, Charlie ; Michie, Caroline O. ; Roxburgh, Patricia ; Yap, Timothy A. ; Harden, Sharon ; Paul, Jim ; Ragupathy, Kalpana ; Todd, Radha ; Petty, Russell ; Reed, Nick ; Hayward, Richard L. ; Mitchell, Paul ; Rye, Tzyvia ; Schellens, Jan H. M. ; Lubinski, Jan ; Carmichael, James ; Kaye, Stan B. ; Mackean, Melanie ; Ferguson, Michelle. / Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer : an extension of the ovarian BRCAness phenotype. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 15. pp. 2505-2511.
    @article{c36a39f3296e4405830888f1d6157ea9,
    title = "Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer: an extension of the ovarian BRCAness phenotype",
    abstract = "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.",
    keywords = "Adrenal Gland Neoplasms, Adult, Aged, Aged, 80 and over, Brain Neoplasms, Female, Genes, BRCA1, Genes, BRCA2, Genetic Predisposition to Disease, Germ-Line Mutation, Humans, Incidence, Liver Neoplasms, Lung Neoplasms, Middle Aged, Neoplasm Metastasis, Ovarian Neoplasms, Pancreatic Neoplasms, Phenotype, Scotland, Splenic Neoplasms",
    author = "Charlie Gourley and Michie, {Caroline O.} and Patricia Roxburgh and Yap, {Timothy A.} and Sharon Harden and Jim Paul and Kalpana Ragupathy and Radha Todd and Russell Petty and Nick Reed and Hayward, {Richard L.} and Paul Mitchell and Tzyvia Rye and Schellens, {Jan H. M.} and Jan Lubinski and James Carmichael and Kaye, {Stan B.} and Melanie Mackean and Michelle Ferguson",
    year = "2010",
    month = "5",
    day = "20",
    doi = "10.1200/JCO.2009.25.1082",
    language = "English",
    volume = "28",
    pages = "2505--2511",
    journal = "Journal of Clinical Oncology",
    issn = "0732-183X",
    publisher = "American Society of Clinical Oncology",
    number = "15",

    }

    Gourley, C, Michie, CO, Roxburgh, P, Yap, TA, Harden, S, Paul, J, Ragupathy, K, Todd, R, Petty, R, Reed, N, Hayward, RL, Mitchell, P, Rye, T, Schellens, JHM, Lubinski, J, Carmichael, J, Kaye, SB, Mackean, M & Ferguson, M 2010, 'Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer: an extension of the ovarian BRCAness phenotype', Journal of Clinical Oncology, vol. 28, no. 15, pp. 2505-2511. https://doi.org/10.1200/JCO.2009.25.1082

    Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer : an extension of the ovarian BRCAness phenotype. / Gourley, Charlie (Lead / Corresponding author); Michie, Caroline O.; Roxburgh, Patricia; Yap, Timothy A.; Harden, Sharon; Paul, Jim; Ragupathy, Kalpana; Todd, Radha; Petty, Russell; Reed, Nick; Hayward, Richard L.; Mitchell, Paul; Rye, Tzyvia; Schellens, Jan H. M.; Lubinski, Jan; Carmichael, James; Kaye, Stan B.; Mackean, Melanie; Ferguson, Michelle.

    In: Journal of Clinical Oncology, Vol. 28, No. 15, 20.05.2010, p. 2505-2511.

    Research output: Contribution to journalArticle

    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

    VL - 28

    SP - 2505

    EP - 2511

    JO - Journal of Clinical Oncology

    JF - Journal of Clinical Oncology

    SN - 0732-183X

    IS - 15

    ER -