Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution

2020 ◽  
Author(s):  
Yusuke Kobayashi ◽  
Akira Hirasawa ◽  
Tatsuyuki Chiyoda ◽  
Arisa Ueki ◽  
Kenta Masuda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cohort Study ◽  
Primary Prevention ◽  
Hormone Replacement ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
History Of ◽  
First Time ◽  
Risk Reducing

Abstract Background Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast–ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast–ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. Methods To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. Results The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38–58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. Conclusions Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

scholarly journals Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity!

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq
Keyword(s):  
Breast Cancer ◽  
Brca1 And Brca2 ◽  
Healthy Women ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Risk Reducing ◽  
Current Guidelines ◽  
Missed Opportunity

Since the identification of BRCA1 and BRCA2 genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like BRCA1 and BRCA2, is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

scholarly journals Three Cases of Breast Cancer in a Family with Hereditary Breast and Ovarian Cancer Syndrome Undergoing Risk-reducing Salpingo-oophorectomy

2019 ◽  
Vol 80 (3) ◽  
pp. 499-502
Author(s):  
Miki NAGATSUKA ◽  
Masami MATSUZAKI ◽  
Naoto KATAGATA ◽  
Takeshi SAKUMA ◽  
Mitsuhiro NIHEI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Risk Reducing

scholarly journals Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant

2020 ◽  
Vol 52 (3) ◽  
pp. 680-688
Author(s):  
Hyung Seok Park ◽  
Jai Min Ryu ◽  
Ji Soo Park ◽  
Seock-Ah Im ◽  
So-Youn Jung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Triple Negative ◽  
Cumulative Risk ◽  
Pathogenic Mutation ◽  
Personal History ◽  
Clinicopathologic Characteristics ◽  
Significant Difference ◽  
History Of ◽  
Risk Reducing

PurposeRecent studies revealed the <i>BRCA1</i> c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other <i>BRCA1</i>/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.Materials and MethodsThe data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.ResultsThe median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with <i>BRCA1</i> carriers and showed higher penetrance of OC than patients with other <i>BRCA1</i> mutations.ConclusionL1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

scholarly journals Breast and ovarian cancer risk reduction options for women with pathogenic variables in the brca1 and brca2 genes

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Sandro Vinícius Machado Melo ◽  
Thamyse Fernanda de Sa Dassie ◽  
Felipe Eduardo Martins de Andrade ◽  
Erica Maria Monteiro Santos ◽  
Benedito Mauro Rossi
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Risk Reduction ◽  
Surgical Management ◽  
Tertiary Hospital ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
Brca1 And Brca2 Genes ◽  
Risk Reduction Measures ◽  
Risk Reducing

Introduction: Most breast and ovarian cancers in women are sporadic. However, five to ten percent of these individuals may have an inherited predisposition to cancer (Famorca-Tram, 2015). Women with pathogenic variants in BRCA1 are at risk of breast cancer of up to 72% and of ovarian cancer of up to 44%. Pathogenic variants of the BRCA2 gene increase the risk of breast cancer by up to 69% and of ovarian cancer by up to 25%. Risk reduction measures include: risk-reducing mastectomy, salpingo-oophorectomy, and chemoprevention. For women who do not choose any of these measures, follow-up with periodic examinations is necessary. In this work, the risk reduction measures adopted by 52 women with pathogenic variants in BRCA1 or BRCA2 in a tertiary hospital in São Paulo, Brazil, are analyzed. In addition, it was analyzed what factors could influence the risk-reducing measure adopted. Materials and methods: cross-sectional study with a sample of 52 women with pathogenic variants identified in the BRCA1 and BRCA2 genes seen at a tertiary hospital. Results: 80.8% opted for surgical management as a risk-reducing measure, with 46.2% of women having had prophylactic mastectomy, 11.5% having had bilateral salpingo-oophorectomy, and 23.1% having undergone both surgical procedures. Non-surgical management occurred in 19.2% of the cases, with 8% (3 cases) undergoing chemoprophylaxis with tamoxifen and 15.4% undergoing surveillance. Conclusion: Most patients opted for surgical intervention, with risk-reducing mastectomy being the most frequent one, followed by salpingo-oophorectomy. When testing was not requested by the geneticist, there was a greater tendency toward the surgical option.

Influence of young age at diagnosis and family history of breast or ovarian cancer on breast cancer outcomes in a population-based cohort study

2006 ◽  
Vol 105 (1) ◽  
pp. 69-80 ◽  
Author(s):  
Jane C. Figueiredo ◽  
Marguerite Ennis ◽  
Julia A. Knight ◽  
John R. McLaughlin ◽  
Nicky Hood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cohort Study ◽  
Family History ◽  
Population Based ◽  
Young Age ◽  
Age At Diagnosis ◽  
Cancer Outcomes ◽  
Breast Cancer Outcomes ◽  
History Of

scholarly journals Literature Review of BARD1 as a Cancer Predisposing Gene with a Focus on Breast and Ovarian Cancers

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 856 ◽  
Author(s):  
Wejdan M. Alenezi ◽  
Caitlin T. Fierheller ◽  
Neil Recio ◽  
Patricia N. Tonin
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Protein Function ◽  
Association Studies ◽  
Study Groups ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
Germline Variants ◽  
Family Based

Soon after the discovery of BRCA1 and BRCA2 over 20 years ago, it became apparent that not all hereditary breast and/or ovarian cancer syndrome families were explained by germline variants in these cancer predisposing genes, suggesting that other such genes have yet to be discovered. BRCA1-associated ring domain (BARD1), a direct interacting partner of BRCA1, was one of the earliest candidates investigated. Sequencing analyses revealed that potentially pathogenic BARD1 variants likely conferred a low–moderate risk to hereditary breast cancer, but this association is inconsistent. Here, we review studies of BARD1 as a cancer predisposing gene and illustrate the challenge of discovering additional cancer risk genes for hereditary breast and/or ovarian cancer. We selected peer reviewed research articles that focused on three themes: (i) sequence analyses of BARD1 to identify potentially pathogenic germline variants in adult hereditary cancer syndromes; (ii) biological assays of BARD1 variants to assess their effect on protein function; and (iii) association studies of BARD1 variants in family-based and case-control study groups to assess cancer risk. In conclusion, BARD1 is likely to be a low–moderate penetrance breast cancer risk gene.

scholarly journals Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases

2019 ◽  
Vol 56 (5) ◽  
pp. 301-307 ◽  
Author(s):  
Robert D Morgan ◽  
George J Burghel ◽  
Nicola Flaum ◽  
Michael Bulman ◽  
Andrew R Clamp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Epithelial Ovarian Cancer ◽  
Medical History ◽  
Progression Free Survival ◽  
Cancer Syndrome ◽  
Platinum Sensitive ◽  
Endometrioid Ovarian Carcinoma ◽  
History Of

IntroductionPoly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.MethodsA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification.ResultsFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ≥15 points (14%).DiscussionOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a >10% prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.

Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study

The Lancet ◽  
2002 ◽  
Vol 360 (9337) ◽  
pp. 891-894 ◽  
Author(s):  
Kjell Bergfeldt ◽  
Bosse Rydh ◽  
Fredrik Granath ◽  
Henrik Grönberg ◽  
Lukman Thalib ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cohort Study ◽  
Family History ◽  
Cancer Patients ◽  
Population Based ◽  
Breast Cancer Patients ◽  
History Of
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