Originally published as JCO Early Release 10.1200/JCO.2008.16.1703 on October 27 2008

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"BRCAness" Syndrome in Ovarian Cancer: A Case-Control Study Describing the Clinical Features and Outcome of Patients With Epithelial Ovarian Cancer Associated With BRCA1 and BRCA2 Mutations

David S.P. Tan, Christian Rothermundt, Karen Thomas, Elizabeth Bancroft, Rosalind Eeles, Susan Shanley, Audrey Ardern-Jones, Andrew Norman, Stanley B. Kaye, Martin E. Gore

From the Gynaecological Oncology and Cancer Genetics Units, Royal Marsden Hospital, London; Section of Medicine, Institute for Cancer Research; Department of Medical Statistics, Royal Marsden Hospital; and the Translational Cancer Genetics Team, The Institute of Cancer Research, Surrey, United Kingdom

Corresponding author: Martin E. Gore, MD, PhD, The Royal Marsden Hospital, Gynecological Oncology Unit, Fulham Road, London SW3 6JJ, United Kingdom; e-mail: martin.gore{at}rmh.nhs.uk

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 (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.

published online ahead of print at www.jco.org on October 27, 2008

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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