Clinical outcome in patients with primary epithelial ovarian cancer and germline BRCA1/2-mutation – real life data

Ataseven, Beyhan; Tripon, D; Schwameis, Richard; Harter, Philipp; Rhiem, Kerstin; Schneider, Stephanie; Heikaus, Sebastian; Baert, Thaïs; Francesco, Alesina Pier; Heitz, Florian; Traut, Alexander; Groeben, Harald-Thomas; Schmutzler, Rita K.; Bois, Andreas du

doi:10.1016/j.ygyno.2021.09.004

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…Our results are in line with a number of previous studies. Studies with limited follow-up periods showed improved PFS and OS–with comparable periods without progression and time till death as seen in our study–for BRCA1- associated EOC patients [ 23 ], BRCA2- associated patients [ 23 , 30 ], or combined BRCA1/2 cohorts [ 10 , 22 , 24 – 26 ]. Studies with long-term periods of follow-up showed that improved overall survival seems to be mainly driven by the first five years after diagnosis, with no benefit for those surviving that first period [ 31 , 33 , 36 ], or even worse OS afterwards [ 32 ], as observed in the current study.…”

Section: Discussionsupporting

confidence: 80%

“…In a previous study the only independent prognostic factor for survival in BRCA1/2 gPV carriers was the extent of debulking at primary surgery, with better survival for patients without macroscopic disease [ 10 ]. Recently, Ataseven et al confirmed that complete macroscopic tumor resection is a strong prognostic factor in patients with EOC, regardless of BRCA status [ 26 ]. In the current study we did adjust for debulking surgery (yes/no), but the amount of residual disease may be more important in this respect.…”

Section: Discussionmentioning

confidence: 99%

“…This may lead to higher response rates to first-line platinum-based chemotherapy–which causes double-strand DNA breaks–and thus to improved survival [ 22 – 24 ]. Indeed, some studies have reported better survival for BRCA- associated EOC patients than for sporadic patients [ 10 , 22 – 26 ], although the reported results are not consistent [ 27 – 29 ]. Survival benefit may be limited to BRCA2 gPV carriers [ 30 ], or only applicable to the first five to ten years [ 31 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study

et al. 2022

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Introduction Germline BRCA1/2-associated epithelial ovarian cancer has been associated with better progression-free survival and overall survival than sporadic epithelial ovarian cancer, but conclusive data are lacking. Methods We matched 389 BRCA1-associated and 123 BRCA2-associated epithelial ovarian cancer patients 1:1 to sporadic epithelial ovarian cancer patients on year of birth, year of diagnosis, and FIGO stage (< = IIA/> = IIB). Germline DNA test was performed before or after epithelial ovarian cancer diagnosis. All patients received chemotherapy. We used Cox proportional hazards models to estimate the associations between mutation status (BRCA1 or BRCA2 versus sporadic) and progression-free survival and overall survival. To investigate whether DNA testing after epithelial ovarian cancer diagnosis resulted in survival bias, we performed additional analyses limited to BRCA1/2-associated epithelial ovarian cancer patients with a DNA test result before cancer diagnosis (n = 73 BRCA1; n = 9 BRCA2) and their matched sporadic controls. Results The median follow-up was 4.4 years (range 0.1–30.1). During the first three years after epithelial ovarian cancer diagnosis, progression-free survival was better for BRCA1 (HR 0.88, 95% CI 0.74–1.04) and BRCA2 (HR 0.58, 95% CI 0.41–0.81) patients than for sporadic patients. Overall survival was better during the first six years after epithelial ovarian cancer for BRCA1 (HR 0.7, 95% CI 0.58–0.84) and BRCA2 (HR 0.41, 95% CI 0.29–0.59) patients. After surviving these years, survival benefits disappeared or were in favor of the sporadic patients. Conclusion For epithelial ovarian cancer patients who received chemotherapy, we confirmed survival benefit for BRCA1 and BRCA2 germline pathogenic variant carriers. This may indicate higher sensitivity to chemotherapy, both in first line treatment and in the recurrent setting. The observed benefit appears to be limited to a relatively short period after epithelial ovarian cancer diagnosis.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study

et al. 2022

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“…The missing report of BRCA status due to study utilizing a retrospective cohort is an empirical limitation. However, BRCA mutation status has been shown not to be associated with improved surgical outcome by the studies of Dimitrova et al [41] and Ataseven et al [42] Various institutions attempted an optimal debulking signature before, successfully identifying prognostic biomarkers for total macroscopic clearance [43]. The studies of Sood et al [17], Riester et al [14], and Tothill et al [24] show overlaps with our results, though both Tothill and Riester included all FIGO stages.…”

Section: Results Strengths and Limitationssupporting

confidence: 62%

Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer

Keunecke

Kulbe

Dreher

et al. 2022

Gynecologic Oncology

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“…In a recently published study by Ataseven et al, these findings were largely confirmed in a great population of 1221 patients with pOC disease. 26 Similarly to our findings, the BRCAmut cohort FIG. 4 PFS after surgery for first OC recurrence between the BRCAmut and BRCAwt cohorts showed higher rates of complete tumor resection compared with their BRCAwt counterparts but did not reach statistical significance, and surgical complexity was not significantly different between both groups.…”

Section: Results In the Context Of Published Literaturesupporting

confidence: 85%

Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium

et al. 2022

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Background This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). Patients and Methods Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. Results Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. Conclusions Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.

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Clinical outcome in patients with primary epithelial ovarian cancer and germline BRCA1/2-mutation – real life data

Cited by 11 publications

References 28 publications

Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study

Progression-free survival and overall survival after BRCA1/2-associated epithelial ovarian cancer: A matched cohort study

Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer

Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium

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