Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations

Singh, Jaya; Thota, Nishita; Singh, Shashikant; Padhi, Shila; Mohan, Puja; Deshwal, Shivani; Sur, Soumit; Ghosh, Mithua; Agarwal, Amit; Sarin, Ramesh; Ahmed, Rosina; Almel, Sachin; Chakraborti, Basumita; Raina, Vinod; DadiReddy, Praveen K; Smruti, B K; Rajappa, Senthil; Dodagoudar, Chandragouda; Aggarwal, Sandeep; Singhal, Manish; Joshi, Anuradha Rajiv; Kumar, Rajeev; Kumar, Abhishek; Mishra, Deepak Kumar; Arora, Neeraj; Karaba, Aarati; Sankaran, Satish; Katragadda, Shanmukh; Ghosh, Arunabha; Veeramachaneni, Vamsi; Hariharan, Ramesh; Mannan, Ashraf U.

doi:10.1007/s10549-018-4726-x

Cited by 67 publications

(79 citation statements)

References 29 publications

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“…and BRCA2 mutations in a cohort of Nigerian patients with breast cancer, and mutation rates as high as 25% are reported in patients with breast and ovarian cancer in India. 7,8 These rates are comparable to the BRCA1 and BRCA2 mutation rates initially characterized in patients of Ashkenazi ancestry with breast cancer. Large biobanking studies of unselected general populations are also finding higher frequencies of BRCA1 and BRCA2 mutations than expected.…”

supporting

confidence: 56%

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

2019

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, issue of JAMA, the US Preventive Services Task Force (USPSTF) 1 offers updated recommendations for risk assessment, counseling, and genetic testing for the BRCA1 and BRCA2 genes. As in 2013, the USPSTF recommends risk assessment for women with family histories of breast, ovarian, tubal, or peritoneal cancers using risk stratification tools and offering those with positive results genetic counseling and possible testing (Grade B recommendation). The USPSTF continues to recommend against large-scale population risk assessment (Grade D recommendation). The 2019 recommendations explicitly add ethnicities and ancestries associated with pathogenic BRCA1 or BRCA2 gene variants (eg, Ashkenazi Jewish) as an indicator for risk assessment, dramatically expanding the number of testable patients in the primary care setting from the 2013 recommendations. Importantly, the USPSTF emphasizes that "Genetic counseling…should be done by trained health professionals, including trained primary care providers." With the increase in women eligible for genetic counseling and testing under these recommendations and the explicit directive for primary care practitioners (PCPs) to consider clinical genetics training per the 2019 USPSTF recommendations, the oncology community should welcome the opportunity to better integrate comprehensive cancer risk assessment and genetic testing for BRCA1 and BRCA2 into routine preventive medicine.

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supporting

confidence: 56%

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

2019

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“…Second, the present study population did not include a sufficient sample of histological subtypes other than HGSC; this limitation impairs the ability to capture the mutational landscape of these tumors. Third, as reported previously (58)(59)(60)(61). a multigene panel for germline and/or somatic testing would probably be cost effective, providing a substantial rate of clinically actionable pathogenic variants (62).…”

Section: Discussionmentioning

confidence: 74%

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

You

et al. 2020

Front. Oncol.

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Objective: Despite several nationwide cohort studies of germline BRCA1/2 mutations and several small cohort studies of somatic BRCA1/2 mutations in Chinese epithelial ovarian cancer (EOC) patients, little is known about the impact of these findings on survival outcomes in this population. In this study of 172 retrospectively recruited Chinese EOC patients, germline and somatic BRCA1/2 mutations and their value for predicting survival outcomes were evaluated. Methods: Unselected patients who visited the study center from January 1, 2011, to January 1, 2015, were recruited and asked to provide peripheral blood samples for this study if they were pathologically confirmed to have primary EOC. All patients received staging surgeries or debulking surgeries involving systemic platinum-based chemotherapy, and the patients were then followed up to December 1, 2017. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections and peripheral blood and sequenced for somatic and germline testing, respectively. The demographic and clinicopathological characteristics of the patients were collected to analyze the distribution of BRCA mutations in subgroups. Survival outcomes were compared among various BRCA mutation statuses using univariate and multivariate models. Results: In 58 (33.7%) patients, 63 variants were identified, including variants of unknown significance (VUS) in 18 patients (10.5%) and pathogenic or likely pathogenic variants in a partially overlapping set of 41 patients (23.8%). Germline BRCA mutations, somatic BRCA mutations, BRCA1 mutations in general, and BRCA2 mutations in general were found in 35 (20.3%), 7 (4.1%), 28 (16.3%), and 13 (7.6%) patients, respectively. Five recurrent mutations were identified. Personal and family cancer histories as well as hereditary breast and ovarian cancer (HBOC) criteria were associated with deleterious BRCA mutations both overall and in the germline specifically, whereas only age at diagnosis of EOC was associated with somatic BRCA mutations. In univariate and Cox regression analyses, patients with BRCA1/2 mutations in general had significant improvements in progression-free survival (PFS) and overall survival (OS). You et al. Germline and Somatic BRCA1/2 Mutations in EOC Conclusions: In Chinese EOC patients, the distributions and risk factors associated with germline and somatic BRCA1/2 mutations were similar to those previously reported in international studies. Deleterious BRCA mutations in general were associated with improved survival outcomes in this cohort.

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“…The comparison aimed to determine the similarities and differences between Chinese and the non‐Chinese Asian populations; Indian population: India has the 2nd largest population in the world, with highly diversified genetic background. Several large‐scale BRCA studies were reported recently with substantial BRCA data collected from the Indian patients . The comparison aimed to determine the similarities and differences between Chinese and Indian populations, the two largest populations in the world.…”

Section: Resultsmentioning

confidence: 99%

“…This variant had the highest prevalence of 5.6% (15 out of 266 detected by five studies). It is a stop-gain pathogenic mutation, present in the BIC, BMD, LOVD, ClinVar, BED databases and was reported as a Chinese founder mutation by a previous study (31 (2 out of 99), is pathogenic, and is present in the BMD, ClinVar, BED and LOVD databases.…”

Section: Comparison In Founder Mutationsmentioning

confidence: 96%

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Germline variation in BRCA1/2 is highly ethnic‐specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients

Bhaskaran

Chandratre

Gupta

et al. 2019

Intl Journal of Cancer

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BRCA1 and BRCA2 play essential roles in maintaining the genome stability. Pathogenic germline mutations in these two genes disrupt their function, lead to genome instability and increase the risk of developing breast and ovarian cancers. BRCA mutations have been extensively screened in Caucasian populations, and the resulting information are used globally as the standard reference in clinical diagnosis, treatment and prevention of BRCA ‐related cancers. Recent studies suggest that BRCA mutations can be ethnic‐specific, raising the question whether a Caucasian‐based BRCA mutation information can be used as a universal standard worldwide, or whether an ethnicity‐based BRCA mutation information system need to be developed for the corresponding ethnic populations. In this study, we used Chinese population as a model to test ethnicity‐specific BRCA mutations considering that China has one of the latest numbers of breast cancer patients therefore BRCA mutation carriers. Through comprehensive data mining, standardization and annotation, we collected 1,088 distinct BRCA variants derived from over 30,000 Chinese individuals, one of the largest BRCA data set from a non‐Caucasian population covering nearly all known BRCA variants in the Chinese population ( https://dbBRCA-Chinese.fhs.umac.mo ). Using this data, we performed multi‐layered analyses to determine the similarities and differences of BRCA variation between Chinese and non‐Chinese ethnic populations. The results show the substantial differences of BRCA data between Chinese and non‐Chinese ethnicities. Our study indicates that the current Caucasian population‐based BRCA data is not adequate to represent the BRCA status in non‐Caucasian populations. Therefore, ethnic‐based BRCA standards need to be established to serve for the non‐Caucasian populations.

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Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations

Cited by 67 publications

References 29 publications

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer

Germline variation in BRCA1/2 is highly ethnic‐specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients

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