Cancer Research, Statistics, and Treatment

: 2020  |  Volume : 3  |  Issue : 2  |  Page : 374--375

Hereditary breast-ovarian cancer syndrome

Anvesh Rathore1, Subhash Ranjan2, AP Dubey3,  
1 Department of Medical Oncology, Army Hospital (R and R), New Delhi, India
2 Department of Medical Oncology, Command Hospital (EC), Kolkata, West Bengal, India
3 Department of Medical Oncology, Shanti Mukund Hospital, New Delhi, India

Correspondence Address:
Anvesh Rathore
Army Hospital (R and R) New Delhi - 110 010

How to cite this article:
Rathore A, Ranjan S, Dubey A P. Hereditary breast-ovarian cancer syndrome.Cancer Res Stat Treat 2020;3:374-375

How to cite this URL:
Rathore A, Ranjan S, Dubey A P. Hereditary breast-ovarian cancer syndrome. Cancer Res Stat Treat [serial online] 2020 [cited 2022 Jul 1 ];3:374-375
Available from:

Full Text

I have read the original article, 'Spectrum of germline BRCA mutations in hereditary breast and ovarian cancer syndrome in Indian population: A central reference laboratory experience,' published in the last issue of the journal by Chheda et al. and the accompanying editorial,[1],[2] I congratulate the author and the team for their valuable article which is an important contribution to the understanding of hereditary breast and ovarian cancer (HBOC).

Breast cancer is the most common cancer in Indian women, with an incidence of 25.8 per 100,000 women and a mortality of 12.7 per 100,000 women. As per the literature world over, HBOC syndrome accounts for 5%–10% of breast cancers. Mutations of BRCA1 and BRCA2 genes encode for 85% of such cases. The lifetime risk in BRCA1 or 2 mutation carriers of developing breast cancer is 45%–80% and that of ovarian cancer is 20%-40%.

Apart from increasing the risk of breast and ovarian cancer, HBOC is also characterized by an increased risk for male breast cancer (1.2% and 8.9%, for BRCA1 and 2 respectively) prostate cancer (8.6% and 20%, for BRCA1 and 2 respectively), pancreatic cancer (1%–3% and 2%-7% respectively), and melanoma. Hence, BRCA1- and BRCA2-associated HBOC should be suspected and is recommended as per the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian.[3]

The diagnosis of BRCA1- and BRCA2-associated HBOC is established in a proband by identification of a heterozygous germline pathogenic variant in BRCA1 or BRCA2 on molecular genetic testing. Molecular testing is most likely to be informative in an individual with BRCA1/2-associated cancer (e.g., breast cancer at age <50 years, ovarian cancer) and is often referred to as the 'best test candidate.' Thus, molecular genetic testing ideally should be performed initially on the 'best test candidate' as opposed to a family member who may have unrelated cancer or who may not have a personal history of cancer. However, if the 'best test candidate' is not available, molecular testing may be performed on another individual, without a cancer history, with the understanding that failure to detect a pathogenic variant does not eliminate the possibility of a BRCA1 or BRCA2 pathogenic variant being present in the family. Molecular testing approaches can include a BRCA1 and BRCA2 gene panel and the use of a multigene panel.[4]

Chheda et al. reported a study conducted in India, in which 160 women were subjected to genetic testing for BRCA1 and BRCA2 mutations using Sanger sequencing and next-generation sequencing methods. Pathogenic variants were found among 34.5% of cancer-affected patients and 25% in cancer-unaffected female relatives with HBOC family history. Pathogenic variants in breast cancer cases (31.5%) were lower than ovarian cancer cases (39.5%). BRCA1 mutations were almost five times higher than BRCA2 mutations in stand-alone cases of ovarian cancer. A spectrum of 20 different pathogenic variants was identified in BRCA1 and 14 in BRCA2.

Differentiating between clinically significant changes and benign nonpathogenic variations, termed as variants of unknown significance (VUS) in BRCA1/2, is one of the difficulties faced in clinical practice. Genetic testing has revealed that approximately 13% of BRCA1 and BRCA2 mutations are VUS, implying clinical uncertainty and ambiguity in risk assessment of tested individuals. The molecular profile of selective cohort (HBOC probands) shows that the prevalence of pathogenic variants in BRCA1 and BRCA2 is high in the Indian population.

The spectrum of BRCA variants is highly diverse, especially in the Indian scenario. Hence, it is very important to correctly classify them as pathogenic, VUS, or benign and to have a country-based database to classify them correctly. The knowledge of the pathogenicity and likely pathogenic mutations are useful to predict prognosis, make therapeutic decisions, apply risk reduction strategies in patients, and carry out cost-effective screening in first-degree relatives. This will also aid in management and surveillance, focusing on reducing the risk of breast cancer and may also influence surgical decision-making in newly diagnosed breast cancer and ovarian cancer patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Chheda P, Pande S, Dama T, Vinarkar S, Chanekar M, Limaye S, et al. Spectrum of germline BRCA mutations in hereditary breast and ovarian cancer syndrome in Indian population: A central reference laboratory experience. Cancer Res Stat Treat 2020;3:32-41.
2Akram Hussain SM. Molecular-based screening and therapeutics of breast and ovarian cancer in low-and middle-income countries. Cancer Res Stat Treat 2020;3:81-4.
3Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast cancer linkage consortium. Lancet 1994;343:692-5.
4Manahan ER, Kuerer HM, Sebastian M. Consensus guidelines on genetic testing for hereditary breast cancer from the American society of breast surgeons. Ann Surg Oncol 2019;26:3025-31.