By Mariam Khan
Tue, 10, 21

This week You! looks at how you can stay ahead in the race against breast cancer by learning about inherited gene mutations…



If you had the power to find out anything about your health, would you want to know about your chances of getting breast cancer? Or would you tell yourself that you do not need to bother about a problem that does not exist in the present? In the race against cancer, though, we have to be one-step ahead. We cannot afford to ignore cancer otherwise; it has the potential to be merciless.

How the genes work?

Our genes carry codes that tell our cells when to grow and divide. When there are mutations in certain genes, corrupting the important instructions related to cell division, cancer might develop. You can imagine these genes as the accelerator of a car and its brake. Some mutations lead to acceleration of cell-growth while some mutations lead to a brake-failure like situation and uncontrolled cell division – both situations lead to cancer. While every cancer involves a mutation in genes, several mutations are required to result in cancer. We have two copies of most genes and in healthy individuals, if a gene is defected, it is repaired or destroyed, which ensures normal functioning of our bodies. In case of cancer, the aforementioned process fails and both mutated genes survive. The mutations in our genes can be inherited, passed on from our parents, or these can be sporadic, which means acquired later in life due to environmental or lifestyle factors. Around 10 per cent of breast cancers are hereditary. It is important to know your risk of gene mutations because it gives you the power to act and manage risk for yourself, for your children and for your family members.

Harmful mutations in BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) genes can significantly increase a woman’s lifetime risk of developing breast cancer. To understand the risk, we can look at the data for women without BRCA1/2 mutation and those with this mutation.


How many women develop cancer?

Generally, 13 per cent of women will develop breast cancer sometime during their lives. On the other hand, according to an estimate, 55–72 per cent of women with BRCA1 mutation and 45–69 per cent of women with BRCA2 mutation will develop breast cancer during their lifetime. Men and women both can inherit a harmful BRCA1/2 mutation and they may pass the variant to their children. Each child has a 50 per cent chance of inheriting a parent’s variant.

It is important to know that statistics for overall population can only tell us so much about risks for a single person. Particular risk for an individual with a BRCA1/2 mutation depends on a number of factors including environment, family history, and mutations in other genes. While this uncertainty can be frustrating for some, it allows for hope. Having BRCA1/2 mutation does not mean that you will necessarily develop breast cancer. Having this conversation is important because it gives you the opportunity to act and take control of your health.

How can you manage risk?

Knowing about your BRCA1/2 mutation means that you can discuss risk management with a genetic counsellor or a doctor trained to deal with patients with inherited cancers. There are a number of options available to manage your risk, such as, prophylactic surgery, which means removal of tissue at risk, lifestyle changes, and increased surveillance with regular screening, which does not prevent cancer but can help to catch it early for successful treatment. Our readers may be aware of Angelina Jolie’s choice of prophylactic double mastectomy after learning about her increased risk of developing breast cancer because of BRCA 1 mutation.

The role of family history is very important in determining your risk for hereditary breast cancer. Certain characteristics in your family history can indicate that you are at a higher risk for BRCA 1/2 mutation. For example, your risk is increased if you have several relatives with breast cancer, any relatives with ovarian cancer, relatives who were diagnosed with breast cancer at an early age before 50, a relative with both breast and ovarian cancer, a male relative with breast cancer, a relative with cancer in both breasts, and a relative with a known BRCA gene mutation.

In this regard, Dr Usman Rashid, a senior research scientist shared that the largest Pakistani study investigating BRCA1/2 mutations on 539 breast cancer patients of Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore was published in 2019. According to this study, BRCA1/2 mutations account for 24.7 per cent of high-risk breast cancer patients in Pakistan. The highest mutation frequency for BRCA1 was noted in families with both breast and ovarian cancer, followed by families with at least three breast cancer cases, then families with two breast cancer cases, and families with one early-onset breast cancer case under the age of 30 years. This study was based on a tertiary care cancer centre located in Lahore where majority of the patients come from Punjab, followed by the KPK and surrounding areas. It is hoped that construction of a large dedicated cancer centre in Karachi will fill this gap and it will open the opportunity to study cancer in the population of Southern Pakistan.

Who should get tested?

Testing for inherited BRCA1 and BRCA2 variants may be done using a blood sample or a saliva sample and it is being offered by Shaukat Khanum Laboratories. Experts recommend testing only for those who have a higher risk of carrying a harmful BRCA1 or BRCA2 variant, such as those who have a family history of certain cancers. Your doctor may suggest if you are eligible for this testing. If you suspect that your family history puts you at a higher risk of breast cancer, request your doctor to investigate it further. You must remember that if you are eligible for testing, the choice of finding out about your cancer risk is solely yours because it can have life-altering consequences. Nevertheless, you should make an effort to know your risk of breast cancer to be able to act and make a difference in your life and in the lives of your loved ones.

The writer is a LUMS alumna and a community social worker with special interest in public health, philosophy, and human rights.