Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer: an extension of the ovarian BRCAness phenotype

Charlie Gourley; 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

doi: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

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 journal › Article › peer-review

79 Citations (Scopus)

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 language	English
Pages (from-to)	2505-2511
Number of pages	7
Journal	Journal of Clinical Oncology
Volume	28
Issue number	15
DOIs	https://doi.org/10.1200/JCO.2009.25.1082
Publication status	Published - 20 May 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

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10.1200/JCO.2009.25.1082

http://jco.ascopubs.org/content/28/15.toc

Cite this

Gourley, C., Michie, C. O., Roxburgh, P., Yap, T. A., Harden, S., Paul, J., Ragupathy, K., Todd, R., Petty, R., Reed, N., Hayward, R. L., Mitchell, P., Rye, T., Schellens, J. H. M., Lubinski, J., Carmichael, J., Kaye, S. B., 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, 28(15), 2505-2511. https://doi.org/10.1200/JCO.2009.25.1082

@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 = may,

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 = "Lippincott Williams and Wilkins",

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

Research output: Contribution to journal › Article › peer-review

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 -

Increased incidence of visceral metastases in Scottish patients with BRCA1/2-defective ovarian cancer: an extension of the ovarian BRCAness phenotype

Abstract

UN SDGs

Keywords

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