Genetic testing for hereditary breast and ovarian cancer in Indian population: A single institutional study.

e13153 Background: Women with Hereditary breast ovarian cancer have an increased lifetime risk of developing breast, ovarian and other second primary cancers . A number of genes including BRCA 1 & 2 have been implicated in Hereditary Breast Ovarian Cancer. In this background we sought to analyze the genetic pattern of patients who underwent genetic testing as per the NCCN criteria for hereditary breast ovarian cancer syndrome. Methods: All consecutive patients who fit into the NCCN criteria for genetic testing for Hereditary Breast Ovarian Cancer from 2016 to 2018 were referred to our genetic clinic. The data of all the patients who underwent further genetic testing after counselling were collected and analyzed. Results: Out of 155 patients who underwent genetic testing ,131 patients were found eligible for the study.127 were female and 4 were male. There were 27 pathogenic mutations identified while 32 were variants of unknown significance . The remaining 72 were negative for any of the known mutations. 22 were pathogenic for BRCA 1 Mutation , two pathogenic for BRCA 2 and one for TP53 ,PALB2 and ATM each. Out of the 32 VUS, 9 were BRCA 2, 4 in CDH 1, 2 in BRCA1, CHEK2 ,MSH2 and BRIP1 and one each in MLH1, MLH3, ATM, APC, RAD51D, XRCC3, NBN, TP53.Three patients had double VUS reported. BRCA 1 is the most common pathogenic mutation ( 16.79% ) found while BRCA 2 is the most common VUS reported ( 28 %). Conclusions: 20.6 % of eligible patients had pathogenic mutations which is much higher than the western literature. However the VUS rates in Indian population are high 22% owing to a paucity of genetic data of Indian population. Multigene testing helps in identifying other genes asscociated with the Hereditary breast ovarian cancer criteria in addition to BRCA 1 & 2.

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Faculty Opinions recommendation of Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091180.544580 ◽

2007 ◽

Author(s):

Michael Friedlander

Keyword(s):

Ovarian Cancer ◽

Therapeutic Management ◽

Cancer Syndrome ◽

Hereditary Breast Ovarian Cancer

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A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

International Journal of Molecular Sciences ◽

10.3390/ijms22020889 ◽

2021 ◽

Vol 22 (2) ◽

pp. 889

Author(s):

Ava Kwong ◽

Cecilia Y. S. Ho ◽

Vivian Y. Shin ◽

Chun Hang Au ◽

Tsun Leung Chan ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca1 Gene ◽

Pathogenic Mutation ◽

Compound Heterozygous ◽

Strong Family History ◽

Breast And Ovarian Cancer ◽

Pathogenic Mutations ◽

Increased Risk ◽

History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

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Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations

Gynecologic Oncology ◽

10.1016/j.ygyno.2005.01.039 ◽

2005 ◽

Vol 97 (2) ◽

pp. 457-467 ◽

Cited By ~ 59

Author(s):

Murray Joseph Casey ◽

Carrie Synder ◽

Chhanda Bewtra ◽

Steven A. Narod ◽

Patrice Watson ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Syndrome ◽

Brca1 And Brca2 ◽

Prophylactic Oophorectomy ◽

Hereditary Breast Ovarian Cancer ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Prevalence of pathogenic mutations in Korean hereditary breast-ovarian cancer

Annals of Oncology ◽

10.1093/annonc/mdy441.012 ◽

2018 ◽

Vol 29 ◽

pp. ix116

Author(s):

G. Lee ◽

J.H. Kim ◽

S.N. Lee ◽

H. Chae ◽

J. Yoo ◽

...

Keyword(s):

Ovarian Cancer ◽

Hereditary Breast Ovarian Cancer ◽

Pathogenic Mutations

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Is Uterine Papillary Serous Adenocarcinoma a Manifestation of the Hereditary Breast–Ovarian Cancer Syndrome?

Gynecologic Oncology ◽

10.1006/gyno.2000.6003 ◽

2000 ◽

Vol 79 (3) ◽

pp. 477-481 ◽

Cited By ~ 85

Author(s):

Ran Goshen ◽

William Chu ◽

Laurie Elit ◽

Tuya Pal ◽

Jalil Hakimi ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Syndrome ◽

Serous Adenocarcinoma ◽

Hereditary Breast Ovarian Cancer

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Impact of hereditary multigene panel testing for cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.261 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. 261-261

Author(s):

Nimmi S. Kapoor ◽

Jennifer Swisher ◽

Rachel E. McFarland ◽

Mychael Patrick ◽

Lisa D. Curcio

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Survivors ◽

Gene Mutation ◽

Gene Panel ◽

Personal History ◽

Panel Testing ◽

Pathogenic Mutations ◽

Gene Panel Testing ◽

History Of

261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.

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Cost-effectiveness of surveillance and prevention strategies in BRCA 1/2 mutation carriers.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13051 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13051-e13051

Author(s):

Hideko Yamauchi ◽

Chizuko Nakagawa ◽

Makoto Kobayashi ◽

Yusuke Kobayashi ◽

Toshiki Mano ◽

...

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Cost Effective ◽

Breast And Ovarian Cancer ◽

Quality Adjustment ◽

Mutation Carriers ◽

Brca 1 ◽

Brca 2 ◽

Preference Ratings ◽

Risk Reducing

e13051 Background: Cost-effectiveness analysis is important in healthcare, especially in Japan, where preventive measures for carriers of BRCA 1/2 mutations are not covered by health insurance. Methods: We developed Markov models in a simulated cohort of women aged 35–70, and compared outcomes of surveillance with risk-reducing mastectomy at age 35 (RRM), risk-reducing salpingo-oophorectomy at age 45 (RRSO), and both (RRM&RRSO), with quality adjustment. We used breast and ovarian cancer incidence, and adverse event rates from previous studies, adjuvant chemotherapy and hormonal therapy rates from Hereditary Breast and Ovarian Cancer Registration 2015, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology and Ministry of Health, Labour and Welfare, and direct costs in 2016 Japanese yen from St. Luke’s International Hospital and Keio University Hospital. We used preference ratings for both of mutation carriers and controls (without known high risk) from a published study to adjust survival for quality of life (QALYs). Discount rate was 2%. Results: Compared with surveillance, RRSO and RRM & RRSO were dominant (cost-saving and more effective) and RRM was cost effective for BRCA 1 mutation carriers. RRM and RRM & RRSO were dominant, and RRSO was cost effective for BRCA 2 mutation carriers. Among four strategies including surveillance, RRM & RRSO was the most cost effective for BRCA 1 mutation carriers and RRM was the most cost effective for BRCA 2 mutation carriers based on preference ratings of controls. Conclusions: With quality adjustment, all the preventive strategies (RRM, RRSO and RRM&RRSO) were cost effective for BRCA 1 and 2. Using QALYs from the control group, RRM & RRSO for BRCA 1 and RRM for BRCA 2 were the most cost effective. We will use this result to promote insurance coverage for BRCA mutations carriers in Japan.

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Results of NGS panel of hereditary breast and ovarian cancer in Lebanese women.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13045 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13045-e13045

Author(s):

Joseph Al Ajami ◽

Nadine Jalkh ◽

Ghadi Moubarak ◽

Roland Eid ◽

Fady Haddad ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Mutation Rate ◽

Founder Effect ◽

Familial Cancer ◽

Brca1 Gene ◽

Pathogenic Mutation ◽

Genetic Alterations ◽

Breast And Ovarian Cancer ◽

Pathogenic Mutations

e13045 Background: Hereditary breast (BC) and ovarian cancer (OC) genetic alterations are considered the most prevalent among familial cancer. To date, four studies have exposed the mutations related to hereditary BC predisposition in the Lebanese population , with percentage of BRCA-related pathogenic mutations ranging between 5 % and 15 %. Methods: Between 2017 and 2019, 117 patients with high risk hereditary breast and ovarian cancer were referred to undergo the testing at the Unité de Génétique médicale (UGM) of Saint-Joseph University of Beirut, Lebanon. The sequencing was accomplished by using the 21-panel Next-Generation Sequencing (NGS) method for all of our patients, to which we also added the MLPA technique followed by the Sanger sequencing for validation whenever a genetic alteration was found. Results: From 117 Lebanese women with high-risk hereditary breast and ovarian cancer predisposition, 19 pathogenic mutations were identified in this study: 11 BRCA1, 1 BRCA2, 2 PALB2, 1 ATM, 1 CDH1, 1 MSH6, 1 RAD51C, and 1 BRIP1. Among those, 13 patients had BC, one had OC and five were healthy individuals. Five similar mutations were found within the BRCA1 gene, the p.C44F mutation, accounting for 45.4 %, thus suggesting a founder effect. Average age at diagnosis in the BC patients carrying a mutation was 41 years and 38.5% had a triple negative BC. Conclusions: The overall pathogenic mutation rate was equal to 16.2% while the BRCA deleterious mutation rate was 10.3% lower to those reported in the literature. The p.C44F mutation appeared five times suggesting a founder effect. [Table: see text]

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BRCA 1/2 mutations in high-grade serous ovarian cancer (HGS-OC) patients of three Latin American countries: Report of 412 cases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14288 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14288-e14288

Author(s):

Juan Molina ◽

Omar Orlando Castillo Fernandez ◽

Maria Lim ◽

Luis Mas ◽

Ignacio Fernando Veliz ◽

...

Keyword(s):

Ovarian Cancer ◽

Costa Rica ◽

Latin American ◽

Positive Family History ◽

Germline Mutations ◽

High Grade ◽

Serous Ovarian Cancer ◽

Brca 1 ◽

Brca 2 ◽

Latin American Countries

e14288 Background: Ovarian Cancer (OC) is the most common gynecologic cancer in women in the World and with elevated mortality. High Grade Serous Ovarian Cancer (HGS-OC) is a common histotype and closely related with the presence of BCRA abnormalities. This is to our knowledge the first report of a large series of patients with HGS-OC evaluated in Latin-American countries. The study aim was to present the data obtained from Perú, Costa Rica and Panamá from January 2016 to December 2018. Methods: A cross-sectional evaluation was performed in patients diagnosed between 2016 and 2018 with HGS-OC in three countries in Latin America. The patients were selected from Cancer National Reference Centers in Perú, Panamá and Costa Rica. Germline BRCA 1 / 2 mutations were evaluated through Next Generation Sequencing (NGS) in blood samples. Results: During the period 412 HGS-OC were studied. The mean age at diagnosis was 56.55(SD:12.21) years for all the evaluated patients and 55.42(SD:8.60) years in the mutated cases. Pathogenic HGS-OC mutations in germline BRCA 1 / 2 were diagnosed in 72 cases. Germline BRCA 2 mutations were the most frequent abnormality detected in Panama and in Costa Rica with 70.0 %(7/10) and 77.8%(14/18), respectively. However in Perú, germline mutations in BRCA 1 represents the majority of the mutations with 79.3%(35/44). Variants of uncertain significance (VUS) were detected in 3.64 %(15/412). Positive family history for breast or ovarian cancer were detected in 13.8% of patients with pathogenic mutations(10/72). Specific mutation distribution evidenced in Perú that 6 of 44(13.6%) mutated patients had the mutation in BRCA 1 c.2105dupT; 6 patients of 18(33.3%) had the mutation in BRCA 2 c.5303_5304delTT in Costa Rica and 2 cases had the mutation in BRCA1 c.5186C > A in Panama. The rest of mutations were less common. Conclusions: The frequency of Germline mutations BRCA 1 and BRCA 2 in patients with HSG-OC is similar to the reported in developed nations. However, the different mutation profile between the studied countries could be explained by the Latin-American genetic diversity. Most of the mutations we report were not described in previous studies evaluating breast cancer susceptibility.

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