Mutation analysis of the BRCA2 gene in breast/ovarian cancer Spanish families: identification of two new mutations

Introduction. The study of mutation in BRCA1/2 genes was first initiated in the USA and Europe, and later in Russia. Statistics indicate that women with the BRCA1/BRCA2 mutation have a higher risk of breast and/or ovarian cancer than the general population. According to different authors, the average cumulative risk among BRCA1 carriers is 65% (range 44–78%) for breast cancer and 39% (range 18–54%) for ovarian cancer. For mutation carriers in the BRCA2 gene, the risk for breast cancer is 45–49%, while the risk for RNA is 11–18%. However, in patients already diagnosed with breast cancer or ovarian cancer, the risk of a second tumor persists throughout life and may remain high even in old age. Treatment of BRCA-associated breast cancer and/or ovarian cancer is almost the same as treatment for sporadic cancer, and includes surgical, radiation, and drug anticancer therapy. However, there are some features that need to be considered in clinical practice. Clinical case. In this article we present the clinical experience of the treatment of a 32-year-old patient with BRCA1-associated primary multiple synchronous breast cancer and metachronous uterine tube cancer. In July 2015, the patient was diagnosed with synchronous cancer of both breast (Luminal A right breast cancer and Luminal B left breast cancer). As part of a treatment and with the patient’s consent, a bilateral adnexectomy was performed. In the histological examination of the operating material, the uterine tube cancer was diagnosed in situ. From 16.03.2016 to the present time the patient receives adjuvant endocrinotherapy without signs of disease progression. Conclusion. This clinical case study presents the importance of a combined approach to the treatment and prevention of BRCAassociated cancer.

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Decision analysis of prophylactic mastectomy and oophorectomy in BRCA1-positive or BRCA2-positive patients.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.3.979 ◽

1998 ◽

Vol 16 (3) ◽

pp. 979-985 ◽

Cited By ~ 151

Author(s):

V R Grann ◽

K S Panageas ◽

W Whang ◽

K H Antman ◽

A I Neugut

Keyword(s):

Quality Of Life ◽

Ovarian Cancer ◽

High Risk ◽

Surgical Procedures ◽

Brca2 Gene ◽

Cost Effective ◽

Prophylactic Surgery ◽

Breast And Ovarian Cancer ◽

Prophylactic Surgical Procedures

PURPOSE Young Ashkenazi Jewish women or those from high-risk families who test positive for BRCA1 or BRCA2 mutant genes have a significant risk of developing breast or ovarian cancer by the age of 70 years. Many question whether they should have prophylactic surgical procedures, ie, bilateral mastectomy and/or oophorectomy. METHODS A Markov model was developed to determine the survival, quality of life, and cost-effectiveness of prophylactic surgical procedures. The probabilities of developing breast and ovarian cancer were based on literature review among women with the BRCA1 or BRCA2 gene and mortality rates were determined from Surveillance, Epidemiology, and End Results (SEER) data for 1973 to 1992. The costs for hospital and ambulatory care were estimated from Health Care Financing Administration (HCFA) payments in 1995, supplemented by managed care and fee-for-service data. Utility measures for quality-adjusted life-years (QALYs) were explicitly determined using the time-trade off method. Estimated risks for breast and ovarian cancer after prophylactic surgeries were obtained from the literature. RESULTS For a 30-year-old woman, according to her cancer risks, prophylactic oophorectomy improved survival by 0.4 to 2.6 years; mastectomy, by 2.8 to 3.4 years; and mastectomy and oophorectomy, by 3.3 to 6.0 years over surveillance. The QALYs saved were 0.5 for oophorectomy and 1.9 for the combined procedures in the high-risk model. Prophylactic surgeries were cost-effective compared with surveillance for years of life saved, but not for QALYs. CONCLUSION Among women who test positive for a BRCA1 or BRCA2 gene mutation, prophylactic surgery at a young age substantially improves survival, but unless genetic risk of cancer is high, provides no benefit for quality of life. Prophylactic surgery is cost-effective for years of life saved compared with other medical interventions that are deemed cost-effective.

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Mutation analysis of the hMTH1 gene in sporadic human ovarian cancer.

International Journal of Oncology ◽

10.3892/ijo.17.3.467 ◽

2000 ◽

Author(s):

F Takama ◽

T Kanuma ◽

D Wang ◽

J I Nishida ◽

Y Nakabeppu ◽

...

Keyword(s):

Ovarian Cancer ◽

Mutation Analysis ◽

Human Ovarian Cancer

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Correction to: BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report

Pathology & Oncology Research ◽

10.1007/s12253-019-00625-0 ◽

2019 ◽

Vol 26 (3) ◽

pp. 2009-2010

Author(s):

Chiraz Mehemmai ◽

Farid Cherbal ◽

Yosr Hamdi ◽

Abdelmoumene Guedioura ◽

Wassila Benbrahim ◽

...

Keyword(s):

Ovarian Cancer ◽

Mutation Analysis ◽

Germline Mutation ◽

Brca1 And Brca2 ◽

First Report ◽

Hereditary Breast Ovarian Cancer ◽

Eastern Algeria

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Caution Should Be Used When Interpreting Alterations Affecting the Exon 3 of the BRCA2 Gene in Breast/Ovarian Cancer Families

Journal of Clinical Oncology ◽

10.1200/jco.2007.13.4346 ◽

2007 ◽

Vol 25 (31) ◽

pp. 5035-5036 ◽

Cited By ~ 12

Author(s):

Orland Díez ◽

Sara Gutiérrez-Enríquez ◽

Teresa Ramón y Cajal ◽

Carmen Alonso ◽

Judith Balmaña ◽

...

Keyword(s):

Ovarian Cancer ◽

Brca2 Gene

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Germline mutation analysis of BRCA1 and BRCA2 genes in Yugoslav breast/ovarian cancer families.

Oncology Reports ◽

10.3892/or.6.6.1435 ◽

1999 ◽

Author(s):

J Papp ◽

L Raicevic ◽

J Milasin ◽

B Dimitrijevic ◽

S Radulovic ◽

...

Keyword(s):

Ovarian Cancer ◽

Mutation Analysis ◽

Germline Mutation ◽

Brca1 And Brca2 ◽

Brca1 And Brca2 Genes

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Screening of BRCA2 mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16567 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16567-e16567

Author(s):

Monica Zuradelli ◽

Nicolo' Buffi ◽

Paolo Bianchi ◽

Carla Barbara Ripamonti ◽

Monica Barile ◽

...

Keyword(s):

Prostate Cancer ◽

Ovarian Cancer ◽

Screening Program ◽

Brca2 Mutation ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Brca2 Gene ◽

Pathogenic Mutation ◽

Genealogical Trees ◽

Targeted Screening

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( > 4ng/ml and > 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.

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