BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study

Petrillo, Marco; Marchetti, Cláudia; Leo, R. De; Musella, Angela; Capoluongo, Ettore; Paris, Ida; Panici, Pierluigi Benedetti; Scambia, Giovanni; Fagotti, Anna

doi:10.1016/j.ajog.2017.05.036

Cited by 76 publications

(55 citation statements)

References 23 publications

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“…Our conclusions are in agreement with a recent study by Petrillo et al14 According to Petrillo et al,14 non-inferiority of neoadjuvant therapy versus primary surgery in BRCA1/2 -mutated high-grade serous ovarian cancer can be explained by high chemosensitivity of hereditary tumors; that is, in BRCA1/2 mutation carriers neoadjuvant therapy produces the same extent of tumor debulking as primary surgery, while in sporadic cases primary surgery often outperforms neoadjuvant therapy with regard to completeness of tumor removal. It is also possible to speculate that BRCA1/2 mutation carriers benefit from early chemotherapy by controlling systemic disease, while the immediate elimination of distant tumor clones is less critical in sporadic carcinomas.…”

Section: Discussionsupporting

confidence: 94%

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Gorodnova

Sokolenko

et al. 2019

Int J Gynecol Cancer

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ObjectiveTumors arising in BRCA1/2 mutation carriers are characterized by increased platinum sensitivity; however, it is unknown whether this feature should be considered while choosing between primary surgical versus systemic treatment. This study aimed to compare outcomes of ovarian cancer patients undergoing either primary surgery or interval cytoreduction based on BRCA1/2 status.MethodsThe study included consecutive ovarian cancer patients, who were treated at the N.N. Petrov Institute of Oncology (St Petersburg, Russia) from 2000 to 2013 and who underwent complete or optimal cytoreductive surgery. A comparison of disease outcomes was performed for the total group of ovarian cancer patients as well as for 69 BRCA1-mutated and 151 sporadic high-grade serous advanced-stage ovarian carcinomas. Frequency comparisons were performed by Chi-square test or Fisher exact test. Disease-free interval and overall survival were analyzed by Mann-Whitney U-test and Kaplan-Meier method. Hazard ratios were calculated by Cox regression analysis.ResultsThe analysis included 283 consecutive patients who underwent optimal cytoreduction (size of residual tumor <1 cm (n=156)) or complete tumor excision (n=127) on primary surgery (n=168) or after neoadjuvant chemotherapy (n=115). 84 patients carried germline mutation in BRCA1 (n=77) or BRCA2 (n=7) genes, while 199 ovarian cancer patients were classified as sporadic. High-grade serous ovarian cancer patients treated with neoadjuvant chemotherapy had a lower disease-free interval compared with those undergoing primary surgery followed by adjuvant therapy (7.8 vs 14.2 months, p<0.001). This difference was attributed mainly to sporadic cases (5.1 vs 12.2 months, p<0.001), while BRCA1-associated cancers had a similar disease-free interval regardless of the sequence of treatments (12.5 vs 15.8 months, p=0.53). When treated with neoadjuvant chemotherapy, BRCA1-mutated patients had improved overall survival as compared with sporadic cases (45.7 vs 25.3 months, p=0.007), while patients subjected to primary surgery showed similar overall survival irrespective of BRCA1 status (54.6 vs 53.9 months, p=0.56). A total of 29/61 (48%) BRCA1/2-associated patients relapsed as a single local tumor; this was lower in sporadic cancer patients (38/134 (28%); p=0.01).ConclusionIn BRCA1 mutation carriers, the oncologic outcomes are similar when comparing primary surgery versus neoadjuvant chemotherapy. In addition, BRCA1-mutation carriers often have a single site of disease when diagnosed with recurrent ovarian cancer.

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Section: Discussionsupporting

confidence: 94%

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Gorodnova

Sokolenko

et al. 2019

Int J Gynecol Cancer

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“…Moreover, we found that neoadjuvant chemotherapy was independently associated with OS, which was consistent with our previous retrospective study [15]. Likewise, in 2017, Petrillo et al reported that in the subgroup of BRCA1/2 non-mutation carriers, patients with neoadjuvant chemotherapy had a worse PFS than those with primary debulking surgery, but no significant difference was found in BRCA1/2 mutation carriers, nor in the estimation of OS [24].…”

Section: Discussionsupporting

confidence: 81%

Survival Benefit of Germline BRCA Mutation is Associated with Residual Disease in Ovarian Cancer

Shi

Wang

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Prognostic value of germline BRCA1 or BRCA2 (gBRCA1/2) mutations in epithelial ovarian cancer (EOC) remains controversial, especially in the estimation of long-term survival. We previously reported the largest study of gBRCA1/2 mutation prevalence in Chinese EOC patients. The aim of this study is to further illustrate the correlation of residual disease and survival in BRCA-associated EOC in China. Methods: In the current cohort consisting of 615 cases from the Chinese EOC genome-wide association study, we evaluated the association between gBRCA1/2 mutation and clinical outcomes. Results: Overall, we did not find any significant difference between gBRCA1/2 mutation carriers and non-carriers in both progression-free survival (PFS) and overall survival (OS) (19.3 vs. 18.1 months and 77.2 vs. 73.2 months, P=0.528 and 0.147, HR 0.93 and 0.79, 95%CI 0.74-1.17 and 0.57-1.09, respectively). However, within three years after diagnosis, mutation carriers showed a longer OS than non-carriers (P=0.018, HR 0.53, 95%CI 0.31-0.90). Such a survival advantage decreased along with the extension of follow-up time. Quite interestingly, in the subgroup of patients with gross residual disease, mutation carriers had a longer survival than non-carriers (18.5 vs. 15.1 months and 68.5 vs. 54.3 months, P=0.046 and 0.038, HR 0.74 and 0.65, 95% CI 0.55-1.00 and 0.43-0.98, for PFS and OS respectively). Conclusions: Our findings provided the evidence that gBRCA1/2 mutation was not associated with survival in Chinese EOC patients, which possibly attributed to more than 37% of the patients without gross residual disease. Survival benefit of gBRCA1/2 mutation was prominent in ovarian cancer patients with gross residual disease.

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“…However, unlike in breast cancer studies, the status of BRCA1/2 mutations in our study was unrelated to CRS. In previous studies [31,32], patients with germline BRCA1/2 mutations were associated with wider disease diffusion than BRCA wild-type patients in terms of peritoneal spread and incidence of bulky lymph nodes. Furthermore, Soslow et al [33] showed the correlations between the genotype and characteristic morphologic appearance of ovarian cancer.…”

Section: Discussionmentioning

confidence: 85%

Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer

et al. 2020

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Background: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). Methods: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated.Results: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients. Conclusion: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

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BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study

Cited by 76 publications

References 23 publications

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

Survival Benefit of Germline BRCA Mutation is Associated with Residual Disease in Ovarian Cancer

Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer

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