Dataset Information

BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

ABSTRACT:

Purpose

The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design.

Patients and methods

Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed.

Results

Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-gradeserous, 17.1%); [corrected] 44% had no reported family history of breast orovarian cancer.Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations.

Conclusion

BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history.

SUBMITTER: Alsop K

PROVIDER: S-EPMC3413277 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

Alsop Kathryn K Fereday Sian S Meldrum Cliff C deFazio Anna A Emmanuel Catherine C George Joshy J Dobrovic Alexander A Birrer Michael J MJ Webb Penelope M PM Stewart Colin C Friedlander Michael M Fox Stephen S Bowtell David D Mitchell Gillian G

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20120618 21

<h4>Purpose</h4>The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design.<h4>Patients and methods</h4>Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival ...[more]

PMID: 22711857

Similar Datasets

Project description:ObjectiveTo describe the testing rate, patient characteristics, temporal trends, timing, and results of germline and somatic BRCA testing in patients with ovarian cancer using real-world data.MethodsWe included a cross-sectional subset of adult patients diagnosed with ovarian cancer between January 1, 2011, and November 30, 2018, who received frontline treatment and were followed for at least 1 year in a real-world database. The primary outcome was receipt of BRCA testing, classified by biosample source as germline (blood or saliva) or somatic (tissue). Lines of therapy (frontline, second line, third line) were derived based on dates of surgery and chemotherapy. Descriptive statistics were analyzed.ResultsAmong 2,557 patients, 72.2% (n=1,846) had at least one documented BRCA test. Among tested patients, 62.5% (n=1,154) had only germline testing, 10.6% (n=197) had only somatic testing, and 19.9% (n=368) had both. Most patients had testing before (9.7%, n=276) or during (48.6%, n=1,521) frontline therapy, with 17.6% (n=273) tested during second-line and 12.7% (n=129) tested during third-line therapy. Patients who received BRCA testing, compared with patients without testing, were younger (mean age 63 years vs 66 years, P <.001) and were more likely to be treated at an academic practice (10.4% vs 7.0%, P =.01), with differences by Eastern Cooperative Oncology Group performance score ( P <.001), stage of disease ( P <.001), histology ( P <.001), geography ( P <.001), and type of frontline therapy ( P <.001), but no differences based on race or ethnicity. The proportion of patients who received BRCA testing within 1 year of diagnosis increased from 24.6% of patients in 2011 to 75.6% of patients in 2018.ConclusionIn a large cohort of patients with ovarian cancer, significant practice disparities existed in testing for actionable BRCA mutations. Despite increased testing over time, many patients did not receive testing, suggesting missed opportunities to identify patients appropriate for targeted therapy and genetic counseling.

Project description:Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features. Associations between CT features, BRCA mutation status, cytoreductive outcome, and progression-free survival (PFS) were evaluated by using logistic regression and Cox proportional hazards regression, respectively. Results Peritoneal disease (PD) pattern, presence of PD in gastrohepatic ligament, mesenteric involvement, and supradiaphragmatic lymphadenopathy at CT were associated with BRCA mutation status (multiple regression: P < .001 for each CT feature). While clinical and CT features were not associated with cytoreductive outcome for patients with BRCA-mutant HGSOC, presence of PD in lesser sac (odds ratio [OR] = 2.40) and left upper quadrant (OR = 1.19), mesenteric involvement (OR = 7.10), and lymphadenopathy in supradiaphragmatic (OR = 2.83) and suprarenal para-aortic (OR = 4.79) regions were associated with higher odds of incomplete cytoreduction in BRCA wild-type HGSOC (multiple regression: P < .001 each CT feature). Mesenteric involvement at CT was associated with significantly shorter PFS for both patients with BRCA-mutant HGSOC (multiple regression: hazard ratio [HR] = 26.7 P < .001) and those with BRCA wild-type HGSOC (univariate analysis: reader 1, HR = 2.42, P < .001; reader 2, HR = 2.61; P < .001). Conclusion Qualitative CT features differed between patients with BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC. CT indicators of cytoreductive outcome varied according to BRCA mutation status. Mesenteric involvement at CT was an indicator of significantly shorter PFS for both patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. © RSNA, 2017 Online supplemental material is available for this article.

Dataset Information

BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

Purpose

Patients and methods

Results

Conclusion

Publications

BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets