Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Abstract

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 prevention of the disease by decreasing the burden to both family and nation. Results from this preliminary study highlight the importance of genetic counseling, pedigree analysis, and genetic testing. It can be recommended that all oncology units should have a genetic counseling service for providing appropriate support to oncologists, patients, and families to prevent unnecessary testing; however, breast cancer screening program is incomplete without evaluating for hereditary breast and ovarian cancer syndrome.

Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population

“…However, despite the high penetrance and the high frequency of variants found in BRCA1/BRCA2 genes, only about 20% of hereditary BC and OC have been attributed to the presence of pathogenic variants in those genes, moreover, about 5-10% have been associated with other susceptibility genes, such as TP53, STK11, PTEN, ATM, and CHEK2 [14]. Studies have demonstrated molecular diagnosis rates of about 4.6-54% when only BRCA1/BRCA2 are screened, which evidences the association of other less penetrant genes with HBOC pathogenesis [15][16][17][18]. Even though the protocols for clinical management are well established for BRCA1/BRCA2 carriers, patients tested negative for pathogenic BRCA1/BRCA2 variants lack the proper clinical follow-up and genetic counselling when presenting similar clinical characteristics and BC/OC increased risk [19].…”

Oncology Gold Standard™ consensus statement on counseling patients for molecular testing and personalized cancer care

“…The advantage of identifying a family with higher risk of hereditary cancers are: [30,31] a. Identification of which members of cancer has that risk and more importantly which member of the family does not have this risk.…”

“…Yet, it is important to screen and test for hereditary cancer risk in select groups of families -to tailor the screening, diagnosis, treatment, and follow-up recommendations for those with higher risk. [30][31][32]…”

“…For instance, breast cancer patients whose tumors were estrogen receptor positive were given hormonal therapy (e.g., tamoxifen) and those with Her2/neu receptor positivity were treated with monoclonal antibodies (trastuzumab) or small molecule tyrosine kinase inhibitors (lapatinib). [11,18,19,31] Clearly, it has always been the basis of stratified approach to cancer management. Today, this approach has improved outcome in select group of more than 30 cancer types -including lung cancer, head-neck cancer, sarcoma, brain tumors, and ovarian cancer.…”

“…It also empowers the patients and families to be responsible for their choices. [11,18,19,31,38] Take Home Messages 1. Today India sees more than 11 lakh new cancer patients every year.…”