Issue 03 | March 2017

How relevant are BRCA1 and BRCA2 news to India?

Thank you for reading our latest myStrand issue on all things cancer and genetics as seen through an Indian lens. In previous issues we have written about how all cancers have a genetic cause, the role inherited cancer plays in the overall cancer scenario and how you can know whether you have a family history of cancer or not. Now, in hereditary cancer, two genes generally are at the forefront of popular news on inherited cancer and sure enough, they have also featured across many of our articles and blog posts. They are the two Breast Cancer genes BRCA1 and BRCA2. But we all know that many a time new medical findings abroad don’t always translate to the Indian or South East Asian context because let’s face it Indians are different, not just culturally, also genetically.

So how relevant are BRCA1 and BRCA2 in the Indian context? Our first article in this issue will look at the latest studies on this subject and recent consensus from the IMRC on breast cancer in India. For our second article, we’ve picked up the discussion on the price of genetic testing in India highlighted by the discoverer of the BRCA genes, Prof. Mary-Claire King, in her lecture series on hereditary cancer in several Indian cities last month.

Please write to us with any questions or suggestions for topics that you would like to see covered in myStrand. You can reach us at strandlive@strandls.com or through any of the communication channels of our #StayAheadOfCancer campaign.

The myStrand team!

The Indian BRCA Connection

A little BRCA history

First, let us begin with a little history. The BRCA genes and their association with breast cancer were first discovered by a researcher in the US in the 1990s. She is Prof. Mary-Claire King, now Professor of Genome Sciences and Medicine at the University of Washington, and she continues to work on research that establishes a connection between specific genetic mutations and human disease. In her early work, she identified that certain mutations in the BRCA1 gene are to blame for some cases of breast cancer and went on to discover a second gene, BRCA2, where certain mutations also had a cancer-causing effect. A couple of decades on, we now have a catalogue of mutations in both BRCA1 and BRCA2 genes and several other genes that are passed on from generation to generation and are known to cause early-onset breast as well as ovarian cancer. In medical circles, these cases are referred to as hereditary breast and ovarian cancer syndrome (HBOC).

The Indian scenario

In recent years, there has been a string of highly-publicized cases of patients who tested positive for HBOC and how they have dealt with this diagnosis. But the vast majority of these cases are from the West. So how relevant are BRCA1 and BRCA2 mutations in the Indian scenario?

Differing breast cancer mutation profiles in India, Singapore and US
Breast cancer mutation profiles are different in India, Singapore, and US

Recent research conducted in India with a pan-Indian group of 141 breast and ovarian cancer patients has found that it is very relevant indeed! Out of all the mutations found in the investigated genes, the vast majority appeared in the BRCA1 gene, with the gene with the second most mutations was TP53 (hereditary cancer caused by a mutation in this gene are known as Li-Fraumeni syndrome), unlike the North American profile, where mutations in the BRCA1 and BRCA2 genes are the most common. These findings are also reflected in our own clinical practice at Strand Life Sciences where we have recently completed over 1,000 hereditary cancer tests.

Just what the doctor ordered

Genetic testing for breast and ovarian cancer patients with a suspected family history and their family members has become an integrated part of healthcare provision in North America and some European countries with detailed guidelines on when to test, the role of genetic counselling, and what happens after the results are available. In India, where many doctors are still not familiar with genetic testing and its utility for diagnosis and treatment, the picture is less clear. However, the Indian Council of Medical Research (ICMR) published a ‘Consensus Document for Management of Breast Cancer’ in 2016 that includes a separate chapter on hereditary breast cancer.

In this chapter, the contributing doctors also attribute over 50% of hereditary breast cancer cases to mutations in the BRCA1 and BRCA2 genes and that another smaller set of cases is caused by a mutation in TP53, and therefore classified as Li-Fraumeni syndrome. Most importantly, however, the document sets out clear guidelines on how to assess whether a case of breast cancer is likely to be hereditary and in what situations risk assessment and genetic testing should be recommended. The document also clearly presents the recommended screening and preventive options for BRCA mutation carriers or family members of a confirmed HBOC case as follows:

  • Screening for women from HBOC families or known BRCA mutation carriers should start at the age of 25 years or 5 years before the youngest affected member in that family, whichever is earlier. Screening methods include:
    • Monthly breast self-examination
    • Six-monthly clinical breast examination
    • Annual breast imaging, ideally by MRI for younger patients, as breast tissue tends to be denser at a younger age, which makes mammography, clinical examination, and ultrasound less effective in detecting early stages of disease.
  • Cancer prevention:
    • Chemoprevention using tamoxifen
    • Risk-reducing surgery to remove ovaries and fallopian tubes (Salpingo-oophorectomy) at the age of 35-40 years and after completion of childbearing. This reduces the risk of ovarian cancer by 99% and of breast cancer by 50%.
    • Risk-reducing surgery to remove both breasts (Bilateral Prophylactic Mastectomy) with reconstruction surgery.
    • Clinical trials of Platinum agents and PARP inhibitors are underway for women with BRCA1/2-associated hereditary breast or ovarian cancer (Note from the editors: PARP inhibitors are already being used in India in this scenario; you can watch an actual patient story here).

Disclaimer: The information provided in this article is in no way intended to replace expert medical advice. Always discuss the best possible course of action for your situation with your doctor.

Show full article.

What are the BRCA1 and BRCA2 genes?

what-are-brca1-and-brca2-genesBRCA1 and BRCA2 are genes that were named after their involvement in the occurrence of breast cancer was discovered – BReast CAncer 1 (pronounced as ‘bra-ca’ 1) is located on chromosome 17, while BReast CAncer 2 is located on chromosome 13. They belong to a group of genes known as tumor suppressor genes because of their important role in repairing damaged DNA when they function normally. However, when a genetic mutation is present in either one of these two genes, they are no longer able to perform their duties and this leads to an increased risk of breast or ovarian cancer and even some other cancers.

 

The Cost of Genetic Testing in India

Genetic testing is the latest diagnostic technique that is set to revolutionize diagnoses of various diseases as well as provide new options for very specific treatment of each patient. It’s almost like a customized fitting of therapy to disease, quite like getting a bespoke suit tailored for you! Although genetic testing sounds complicated and expensive, it is not. Procedures for sample collection are not much different from existing tests and the actual testing and analysis part has been perfected at Strand Life Sciences. Moreover, prices continue to tumble as scientists, device manufacturers, and testing companies are working hard to make the elusive US$1000 genome (around 60,000 Indian rupees) a reality. In fact, the number of people opting for genetic tests I son the rise.

Meanwhile, a whole gamut of genetic tests has started to flood the Indian healthcare market, ranging from your lifestyle advisor (telling you how good your body is at metabolizing coffee or whether the gym is for you or not), medical diagnostic tests for metabolic disorders, rare diseases and cancers, as well as prognostic tests that tell you whether you are at a higher risk than the average person of getting certain diseases like diabetes, high blood pressure, as well as certain hereditary cancer types. Since there is little or no regulation yet from the Indian government, the genetic testing industry largely depends on self-regulation and the patient is tasked with gathering the necessary information through online searches and advice from their doctors to ensure a given test addresses their specific needs.

So let us look at these different types of genetic tests and their price tags:

  • Genetic Testing for Lifestyle, Nutrition, Fitness: These tests have to be clearly separated from the other two, more medical oriented categories, especially since anyone can order the test without a doctor’s prescription and often still user older test methods. Such tests typically include a single gene, or a small number of genes related to specific aspects of your metabolism and how your body deals with certain nutrients or exercise regimens. Sometimes these tests also include an indicator of a risk to develop diabetes or obesity. Recent prices stated online for such tests range from some 3,000 rupees to close to 20,000 rupees for more comprehensive gene panels. The cost is usually linked to the number of genes being tested and the sky is the limit here.
  • Diagnostic Tests for Metabolic Disorders, Rare Diseases, and Cancer: These tests are usually only prescribed by doctors based on specific symptoms and in the case of cancer, require an actual biopsy of the tumor. Depending on the condition suspected by the physician, a single gene test can be sufficient or a larger panel with many more, up to several hundred genes could be advised. Accordingly prices range from under 10,000 rupees for single gene tests to over 1 lakh rupees for the larger investigational panels. But the impact is huge considering that you are likely going to be able to identify a drug regimen or clinical trial that will give you a chance at significantly improving your quality of life.
  • Prognostic Tests for Hereditary Conditions (including Cancer): These types of tests lie somewhere between the first and second category in that they should be prescribed by a physician but don’t have to be depending on the company providing the test. For example, some of the tests offered by companies focusing on lifestyle genetic testing include genes that predict cancer risk. But the hereditary cancer-focused multi-gene panels typically include anywhere from 20 to 50 genes (typically including the BRCA genes, TP53, PTEN and others) are priced between 20,000 to 60,000 rupees, including Strand Life Sciences’ Hereditary Cancer Test. Of course, single gene tests are also available in this category and would therefore be priced much lower relative to the total number of genes tested.

Sounds like a lot of money for a single test, right? And certainly in the Indian context, such price tags make the tests unaffordable for a large majority of patients. However, once you start looking at the value particularly the diagnostic and hereditary cancer testing categories can give, you might just reconsider.

Take the BRCA genes for example. Knowing your BRCA1 status is not just beneficial if you are in your 30s and not diagnosed with cancer yet, when you might know you have a family history and that nagging doubt of whether it might hit you as well hanging over your head. In this case, the test result will either reassure you that you are not at the significantly higher lifetime risk of getting breast cancer of up to 80% (and up to 50% of getting ovarian cancer), or replacing uncertainty with the opportunity to take charge of your own health with recommended screening and preventive surgery options and making lifestyle changes that minimize your risk. Adopting these recommendations will make it more likely that any cancer is detected early when it is much more treatable or even prevented altogether.

In fact, more recently, doctors in India have also started recommending certain drugs known as PARP inhibitors to breast and ovarian cancer patients who tested positive for BRCA1 or BRCA2 and many of them are seeing a significant improvement in their quality of life as a result. Plus, testing a cancer patient for their BRCA status will provide valuable information to her daughters and sisters and their future healthcare management. This is why Prof. Mary-Claire King, discoverer of the BRCA1 gene and its link to hereditary breast cancer, recommends that all women over 30 should get tested. Albeit, in the case of India, where affordability is still a huge hurdle, she suggests to routinely start testing breast cancer patients to allow them and their immediate family to benefit.

Have questions, or would you like to get more information on this topic? Please do not hesitate to get in touch through our StayAheadOfCancer portal (www.strandls.com/stayaheadofcancer) to make an appointment with a genetic counsellor to discuss your concerns.

Disclaimer: The information provided in this article is in no way intended to replace expert medical advice. Always discuss the best possible course of action for your situation with your doctor.

A Patient Story

Watch this inspirational story of an ovarian cancer survivor who braved the odds and gained a new lease of life thanks to genetic testing and the treatment options it opened up for her. Watch now!