‘Not all BRAC1, BRAC2 mutations result in breast cancer’

“Genetic test for BRCA1/2 is not recommended as a screening test,” said Dr. Vani Parmar, Associate Professor, Department of Surgical Oncology at Tata Memorial Hospital, Mumbai. “We don’t recommend it for individuals who do not have a family history or if they do not already have breast cancer.” However, genetic testing would be recommended for those with breast cancer and aged less than 35 even without a family history.

“All BRCA1/2 alterations do not result in breast cancer,” says Dr. Parmar. Also, the hereditary factor comes into play only in the case of ten per cent of breast cancer patients.

“Never do testing on individuals who want to know if they are at risk of developing breast cancer just because one first-degree relative [like mother or sister] has breast cancer,” emphasised Dr. T. Rajkumar, Professor and Head of the Department of Molecular Oncology, Cancer Institute, Chennai. The reason for this is that in 60-70 per cent cases, the genetic test would only show single nucleotide polymorphism (SNP). The effect of SNPs is not known in about 40-50 per cent of cases.

It is important that a molecular oncologist understands and explains the significance of a genetic test result. There is a need for counselling prior to undergoing the test and before the test result is revealed.

The biggest handicap in the case of India is that we have very little information on specific breast cancer mutations that are common in our population.

In some ethnic groups in the world, specific breast cancer mutations are common in a given population. It is best demonstrated in the case of Ashkenazi Jews, who have been inbreeding over a long period of time. About 2.6 per cent Ashkenazi Jews with hereditary breast cancer carry three specific mutations called founder mutations. The occurrence of these mutations in the general population is just 0.2 per cent, according to a 2007 paper in the journal Annals of Oncology.

A study by Tata Memorial Hospital, Mumbai, found four particular mutations common in a given population. A mutation found in Ashkenazi Jews population was commonly found in a particular sect of Brahmins from the Western coast. “Forty-fifty unrelated families were studied and we found this mutation in this sect all along the western coast, from Maharashtra to Kerala,” said Dr. Rajiv Sarin, Director of ICMR Centre for Cancer Genetics at ACTREC and Tata Memorial Hospital, Mumbai. “The mutation is distinct from Ashkenazi Jews’ and has occurred independently and separately.”

Dr. Rajkumar has also found a mutation specific to Ashkenazi Jews in Indian families. “Of the 30 families found to have deleterious mutations in the BRCA1, BRCA2 genes, eight families have Ashkenazi Jews mutations,” said Dr. Rajkumar. “Their ethnicity in terms of region and religion — Jains, Christians, Hindus — are completely different.”

According to Dr. Rajkumar, it is better to opt for mastectomy rather than breast conservation in the case of breast cancer patients with deleterious mutations of BRCA1, BRCA2. “The chances of breast cancer occurring in the remaining portion of the breast are very high in such patients,” he said. “The ovaries also need to be addressed.”

Explaining the reason why BRCA1, BRCA2 genetic testing is done in people who already have breast cancer, Dr. Rajkumar said: “The genetic test result offers information that will be useful in treating the patient.”

Dr. Rajkumar seeks to dispel the notion that deleterious mutations in BRCA1/2 genes alone are responsible for hereditary breast cancer. “Like BRCA1/2, mutations in p53 gene also put a person in the high-risk category.”

Of the 30 genes that are profiled at Cancer Institute, 20 genes fall in the intermediate-risk category. Of the 20 genes, one or two genes are associated with hereditary breast cancer or ovarian cancers.

“This is a new finding,” he said.

Published in The Hindu on May 19, 2013