Genetic Counseling, Testing, and Management of HBOC in India: An Expert Consensus Document from Indian Society of Medical and Pediatric Oncology (original) (raw)
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Indian Journal of Gynecologic Oncology, 2019
Objectives To identify cases needing genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome among cases of breast and ovarian cancer and assess their acceptability for genetic testing. Materials and Methods One hundred patients of breast and/or ovarian cancer were recruited. A series of family meetings were done with patient and close family members. The first meeting was for pedigree chart preparation and identification of cases for genetic testing (HBOC) as per NCCN 2013 criteria. Second family meeting was held for counselling about genetic testing. Third meeting was held for recording acceptance or refusal for genetic testing. For those refusing the test, reasons for refusal were recorded. Outcome measures including prevalence of high-risk cases, acceptance rate for genetic testing and factors affecting the above acceptance rates among high-risk women were statistically analysed. Results Out of 100 patients of breast and ovarian cancer recruited in the study, 88 were found to be at high risk of HBOC. The most common criterion for high risk among breast cancer cases was age below 45 years. Family history of breast or ovarian cancer was present in 3.03% cases of ovarian cancer and 11.76 cases of breast cancer. Eleven (16.66%) cases of epithelial ovarian carcinoma and six (27.27%) cases of breast carcinoma accepted genetic testing. Socioeconomic status was found to have statistically significant correlation (p \ 0.001 and p = 0.030) with acceptance for genetic testing. Conclusion Though it is a small sample study, there is huge burden of women needing genetic testing for HBOC. There is lack of awareness about familial nature of disease and low acceptance for genetic testing in our population. There is a significant effect of socioeconomic status on acceptance for genetic testing.
Tumor Biology
Global burden of breast cancer is expected to increase to >2 million new cases every year by 2030 and 10% of these are likely to have hereditary breast and ovarian cancer syndrome. Identifying these individuals by pedigree and BRCA1/2 mutation analyses will enable us to offer targeted mutation testing and appropriate counseling. This study from a tertiary care hospital showed that of the 127 breast cancer patients on treatment during 2014–2015, 24 of them fulfilled the criteria of hereditary breast and ovarian cancer syndrome after detailed verbal autopsy and pedigree analysis, and BRCA1 and 2 next-generation sequencing done after pre-test counseling revealed mutations in 13 cases (54%), these included 9 BRCA1 mutations (69%) and 4 BRCA2 mutation (31%). Subsequent post-test counseling recommended targeted mutation analysis for 64 high-risk members in these 13 families with pathogenic mutations, which will help in surveillance for early detection, appropriate management, and preve...
Current Oncology, 2014
Objectives: It is estimated that 1–2% of individuals of Ashkenazi Jewish (AJ) ancestry carry one of three pathogenic founder mutations in BRCA1 and BRCA2. Targeted testing for these mutations (BRCA1 187delAG and 5385insC, and BRCA2 6174delT) is therefore recommended for all AJ breast and ovarian cancer patients, regardless of age of diagnosis or family history. Comprehensive analysis of both genes is recommended for a subset of AJ patients in whom founder mutations are not identified, but estimates of the yield from comprehensive analysis in this population vary widely. Methods: We sought to establish the proportion of non-founder mutations in AJ patients undergoing clinical testing in our laboratory from January 2006 through August 2013. Analysis included AJ patients for whom: (1) comprehensive testing was ordered as the initial test, or (2) founder mutation testing was ordered with instructions to “reflex” to comprehensive analysis if negative. The latter group was limited to case...
Background:BRCA1/BRCA2 mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. Methods: The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. Results: In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services. Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. Conclusions: The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management.
Breast cancer research and treatment, 2018
Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagn...
Current Oncology, 2012
Background: Nearly 15% of DNA tests for BRCA1/2 results in the identification of an unclassified variant (UV). In DNA diagnostic laboratories in The Netherlands, a 4-group classification system (class I to IV ) is in use (Bell et al.). Aim of this study was to investigate whether the UVs in different classes showed a significant difference in their in silico characteristics and would justify current differences in protocols for counselling with respect to communication to the counselees.
Germline BRCA1 Mutation Analysis in Indian Breast/Ovarian Cancer Families
Cancer Biology & Therapy, 2002
Most of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in two tumor suppressor genes BRCA1 and BRCA2. To explore the contribution of BRCA1 mutations to hereditary breast cancer among Indian women, we examined the coding sequence of the BRCA1 gene in 14 breast cancer patients with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation sensitive gel electrophoresis (CSGE) followed by sequencing. Three mutations (21%) in the BRCA1 gene were identified. Two of them are novel mutations of which one is a missense mutation in exon 7 near the RING finger domain, while the other is a one base pair deletion in exon 11 which results in protein truncation. The third mutation, 185delAG, has been previously described in Ashkenazi Jewish families. To our knowledge this is the first report of a study of germline BRCA1 mutation analysis in familial breast cancer in India. Our data from 14 different families suggests a lower prevalence but definite involvement of germline mutations in the BRCA1 gene among Indian women with breast cancer and a family history of breast cancer.
European Journal of Breast Health, 2021
Background: Worldwide genetic counseling practices are variable and often not reported in low-and middle-income countries (LMICs). We present the follow-up genetic counseling, breast screening, risk-reducing salpingo-oophorectomy (RRSO) and contralateral prophylactic mastectomy (CPM) on a cohort of study patients with either BRCA pathogenic mutations or BRCA Variant of Unknown Significance (VUS). Methods: Chart review and phone calls for the collection of information. Out of a cohort of 250 patients, 14 had deleterious mutations and 31 had a VUS of whom 19 had primary early breast cancer. We collected information about genetic counseling, screening, CPM and RRSO. Results: 14 patients with deleterious mutations (7 BRCA1 and 7 BRCA2) and 19 patients with VUS mutations (20 VUS, 4 BRCA1, 16 BRCA2; 1 patient had both) were surveyed. Of 14 patients with BRCA deleterious mutations, 57.14% (8/14 patients) received genetic counseling from their oncologist. 85.71% (12/14) are undergoing mammography screening, 35.71% (5/14) screening breast MRI. 50% of them underwent CPM and 57.14% underwent RRSO. Of 19 patients with VUS mutations, 10.5% received genetic counseling from their oncologist; 78.9% were undergoing regular screening mammogram, 31.5% were undergoing MRI breasts; one patient underwent CPM and two patients RRSO. Conclusions: Within 3 years from knowing they have a mutation, 50% of patients with germline BRCA mutations had undergone CPM and 60% RRSO, the majority of them had screening mammography surveillance but only 50% had screening MRI. Follow-up of patients with VUS with mammography was at 78% rate but MRI was only 31%. Lack of MRI surveillance reflects both limited resources and unsufficient counseling. Genetic counseling was done by medical oncologists which reflects a trend in LMIC and others. Our U n c o r r e c t e d p r o o f Data shows the importance of the need for professional genetic counselors and optimal surveillance in Lebanon and other LMICs.
Journal of Biosciences, 2009
Mutations in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. To explore the contribution of BRCA1 and BRCA2 mutations in the development of hereditary breast cancer among Indian women, we carried out mutation analysis of the BRCA1 and BRCA2 genes in 61 breast or ovarian cancer patients from south India with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation-sensitive gel electrophoresis (CSGE) followed by sequencing. Mutations were identified in 17 patients (28.0%); 15 (24.6%) had BRCA1 mutations and two (3.28%) had BRCA2 mutations. While no specific association between BRCA1 or BRCA2 mutations with cancer type was seen, mutations were more often seen in families with ovarian cancer. While 40% (4/10) and 30.8% (4/12) of families with ovarian or breast and ovarian cancer had mutations, only 23.1% (9/39) of families with breast cancer carried mutations in the BRCA1 and BRCA2 genes. In addition, while BRCA1 mutations were found in all age groups, BRCA2 mutations were found only in the age group of ≤40 years. Of the BRCA1 mutations, there were three novel mutations (295delCA; 4213T→A; 5267T→G) and three mutations that have been reported earlier. Interestingly, 185delAG, a BRCA1 mutation which occurs at a very high frequency in Ashkenazi Jews, was found at a frequency of 16.4% (10/61). There was one novel mutation (4866insT) and one reported mutation in BRCA2. Thus, our study emphasizes the importance of mutation screening in familial breast and/or ovarian cancers, and the potential implications of these findings in genetic counselling and preventive therapy.
Cancer Management and Research
Background: The spectrum of BRCA mutations that predispose to development of breast/ ovarian cancer in Indian population remains unexplored. We report incidence and various types of pathogenic, likely pathogenic and variants of unknown significance (VUS) mutations in BRCA1 and BRCA2 genes observed at a tertiary cancer center in North India. Materials and methods: A total of 206 unrelated breast and/or ovarian cancer patients, who met the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, were screened for germline BRCA1/BRCA 2 mutations on high-throughput sequencing platform; large genomic rearrangements were assessed by multiple ligation probe assay. Mutations were mined in mutational databases, PubMed, and discerned into classes. Furthermore, the clinicopathological correlation of BRCA mutation status with prognostic markers in breast cancer and tumor histology in ovarian cancer was performed. Results: In total, 45/206 and 17/206 cases showed positivity for BRCA1 and BRCA2 mutations, respectively, whereas 1/206 was positive for a mutation in both the genes. Altogether, 33 distinct BRCA1 mutations were observed, among which 27 were deleterious (12 frameshifts, 8 nonsense, 1 missense, 3 splice-site variants, 2 big deletions and 1 large duplication) and 6 were VUS. Five novel BRCA1 mutations (c.541G>T, c.1681delT, c.2295delG, c.4915C>T and exon 23 deletion) were identified. Seven mutations (c.2214_2215insT, c.2295delG, c.3607C>T, c.4158_4162delCTCTC, c.4571C>A, splicesite_3 (C>T) and exon 21-23 duplication) occurred more than once, whereas 16 distinct BRCA2 mutations were noted-9 were lethal (6 frameshifts, 2 nonsense and 1 big deletion) and 7 VUS. One unique pathogenic BRCA2 mutation (c.932_933insT) was recognized. Two mutations (c.9976A>T and c.10089A>G) recurred twice. No significant difference in hormone receptor status was observed among BRCA1 carriers, BRCA2 carriers and noncarriers. Conclusion: We have documented various pathogenic and VUS mutations in BRCA1 and BRCA2 genes observed in the cohort. Six novel mutations were identified. The knowledge shared would assist genetic testing in enabling more focused site-specific screening for mutations in biological relatives.