BRCA Mutations Lessen Protective Effect of Pill against Ovarian Cancer

2001 ◽  
Vol 33 (6) ◽  
pp. 286
Author(s):  
J. Rosenberg
Keyword(s):  
Ovarian Cancer ◽  
Protective Effect ◽  
Brca Mutations

Prognostic influence of BRCA 1 somatic mutations in African Amercian versus Caucasian ovarian cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17054-e17054
Author(s):  
Sareena Singh ◽  
Karen Swarer ◽  
Analisa DiFeo ◽  
Joram Sawady ◽  
Susanna Syriac ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protective Effect ◽  
Tumor Biology ◽  
Progression Free Survival ◽  
Positive Control ◽  
High Grade ◽  
Brca Mutations ◽  
Pathology Laboratory ◽  
Significant Difference ◽  
Brca 1

e17054 Background: Racial disparities in outcomes exist between African-American (AA) and Caucasian (C) patients (pts) with high grade epithelial ovarian cancer (EOC). Not all disparity is explained by socio-economic and access related issues. Many argue that differences in tumor biology also play a role. Germline BRCA mutations confer a protective effect in these pts. Immunohistochemistry (IHC) for BRCA 1 is being developed to detect somatic BRCA1 mutations. Parp-inhibitors have been approved for use in pts with germline and/or somatic BRCA mutations. We describe the first comparison of the prognostic implications of BRCA1 somatic mutation status in tumor samples taken from AA and C EOC pts who underwent primary surgery followed by systemic chemotherapy. Methods: IHC staining of whole tumor sections from AA and C pts was performed using a commercially available monoclonal antibody against BRCA1 (Calbiochem). Staining was scored as: loss, retention, or equivocal in the presence of a positive control. Retention was described as wild-type and loss or equivocal as mutation. Standard statistical analyses were used to correlate race, BRCA1 status, and survival. Results: Tumor from 33 pts (16AA and 17C) was stained and scored. Most pts had Stage III (66.7%) disease and high grade serous subtype (82%). Stage, histology, and debulking status did not differ between groups. Overall, loss of BRCA 1 occurred 16/33 (48.5%) tumors. BRCA1 was mutated more frequently in tumors from AA pts (11/16) compared to C pts (5/17) (p=.024). BRCA 1 mutation conferred a protective effect, with a trend towards improved progression free survival: 9.5 vs 15.8 mos in AA (p=0.44) and 16.5 vs. 21 mos in C pts (p=0.97). No statistically significant difference in OS was seen. Conclusions: We demonstrate that IHC for BRCA 1 mutation is feasible in a standard hospital pathology laboratory. Race based differences in somatic BRCA 1 mutation exist; mutational differences are associated with a trend in improved PFS. A larger cohort is needed to elucidate the true effect of this status on outcome. Conceivably, knowledge of BRCA 1 tumor status could be used to improve outcomes in AA pts who may be able to achieve survival numbers comparable to C pts.

scholarly journals The Prognostic and Predictive Role of Somatic BRCA Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 565
Author(s):  
Angela Toss ◽  
Claudia Piombino ◽  
Elena Tenedini ◽  
Alessandra Bologna ◽  
Elisa Gasparini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Positive Impact ◽  
Progression Free Survival ◽  
Molecular Testing ◽  
Wild Type ◽  
Brca Mutations ◽  
Multicenter Cohort Study ◽  
Advanced Stages ◽  
Predictive Role

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

scholarly journals Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 547
Author(s):  
Iolia Akaev ◽  
Siavash Rahimi ◽  
Olubukola Onifade ◽  
Francis John Edward Gardner ◽  
David Castells-Rufas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unknown Origin ◽  
Parp Inhibitors ◽  
Serous Carcinoma ◽  
High Grade ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Epithelial Cancers ◽  
Pathogenic Variants ◽  
Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

scholarly journals BRCA mutations in Italian breast/ovarian cancer families

2002 ◽  
Vol 10 (2) ◽  
pp. 150-152 ◽  
Author(s):  
Raluca Nedelcu ◽  
Alexander Liede ◽  
Jennifer Aubé ◽  
Amy Finch ◽  
Elaine Kwan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutations

scholarly journals High frequency of BRCA recurrent mutations in a consecutive series of unselected ovarian cancer patients

2020 ◽  
Vol 28 (3) ◽  
pp. 257-266
Author(s):  
Andrei Chicos ◽  
Lucian Negura ◽  
Rares Braescu ◽  
Aliona Morariu ◽  
Anca Negura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Target Population ◽  
Consecutive Series ◽  
Inclusion Criteria ◽  
Brca Testing ◽  
Brca Mutations ◽  
Brca Genes ◽  
Incidence And Mortality ◽  
Recurrent Mutations

AbstractHereditary predisposition to breast and ovarian cancer (HBOC) is diagnosed by molecular analysis of deleterious mutations in BRCA genes, allowing oncogenetic follow-up of patients and of their families. BRCA testing addresses only to HBOC families, using restrictive inclusion criteria based on familial history of cancer and age at diagnosis. Sporadic ovarian cancer has high incidence and mortality in Romania, with low median age of diagnosis and possibly a higher magnitude of hereditary contribution comparing to othe populations. However, sporadic ovarian cancers do not qualify for BRCA testing according to inclusion criteria, and a complete BRCA screening of all cancers is neither feasible nor recommended. Despite the large diversity of BRCA mutations worldwide, some recurrent mutations have higher frequencies in diverse populations. Precisely screening for recurrent mutations in a target population allows to rapidly identifying mutation carriers without sequencing the entire BRCA genes. In Romanian population and neighboring countries, several recurrent mutations have already been described. In a consecutive series of 50 sporadic ovarian cancer patients, not qualifying for BRCA complete testing, we screened for 9 most common BRCA mutations, by multiplex-PCR, RFLP and targeted Sanger sequencing. Our results revealed 6 different BRCA mutations in 8 unrelated patients, with a frequency of 16%, much higher than expected. We further recommend screening for the identified mutations in larger series of cancer patients. The results are highly beneficial to cancer patients, healthy relatives, and overall, considering prevention in cancer a priority, to public health system and future of oncogenetics in Romania

scholarly journals Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

2020 ◽  
Author(s):  
Dorra Ben Ayed-Guerfali ◽  
Wala Ben Kridis-Rejab ◽  
Nihel Ammous-Boukhris ◽  
Wajdi Ayadi ◽  
Slim Charfi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Germline Mutations ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Counseling And Testing ◽  
Recurrent Mutations ◽  
Tunisian Patients ◽  
History Of ◽  
Brca1 Brca2

Abstract Background: The incidence of breast/ovarian cancer is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. Methods: We sequenced the entire coding regions of BRCA1and BRCA2 genes using Next Generation Sequencing (NGS) in 134 selected patients with breast/ovarian cancer. Results: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshisft indel (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A>T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p=0.029) and TNBC cases (p=0.008). In the groups of patients (31-40 y and 41-50 y), BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p=0.001 and p=0.044 respectively).Conclusions: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast /ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of breast/ovarian cancer.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

2021 ◽  
pp. 849-861
Author(s):  
Sudeep Gupta ◽  
Senthil Rajappa ◽  
Suresh Advani ◽  
Amit Agarwal ◽  
Shyam Aggarwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Fallopian Tube Cancer ◽  
Cross Sectional ◽  
Brca2 Mutations ◽  
Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers

2021 ◽  
Author(s):  
Yosr Hamdi ◽  
Najah Mighri ◽  
Maroua Boujemaa ◽  
Nesrine Mejri ◽  
Sonia Ben Nasr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Large Fraction ◽  
Age At Onset ◽  
Tunisian Population ◽  
North African ◽  
Brca Mutations ◽  
Access To Treatment ◽  
Genetic Components ◽  
Ovarian Cancers

Abstract Background Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations. Methods A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have been also investigated. Results 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations. Conclusion Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

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