Why me?

Prof Carol-Ann Benn unlocks the genetic code of who gets breast cancer to resolve the Why me question.

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I’m often asked, “Why did I get cancer? I’ve done everything correct,” or “I know why I got breast cancer, it’s because I hate my mom…don’t eat properly…don’t exercise.”

My answer is, “You have done nothing wrong. Find me a perfect person…still waiting and I don’t see any hands up.” So, getting breast cancer is really like a card game. Let’s call it the five card draw game of life.

But what happens when you are given that hand of cards? Maybe you’ve had a genetictest and pulled the black spot (like in pirate movies) and you have a positive BRCA test; or the geneticist, that you were sent to because you’ve a family history, has told you that you have a gene that puts you at risk for many cancers possibly and you’re thinking…write a will, party hard or don’t have kids.

The five card draw game

The genetic truth is you’re dealt five cards; three you keep and can’t change; two you can change. These cards apply to all aspects of life. There are many five card hands: five cards of health and lifestyle; five cards of relationships, those of worth and life goals.

The cards of breast cancer risk

The first card (you can’t change) is your family history and genetic blueprint. The second card (you can’t change) is your endocrine history (when you start your period, when it stops, ability and timing of having children; breast feeding, etc.) The third card is how you live your life. It doesn’t matter what your genetics are, living your life is what it’s all about in both a good and bad sense. The card you must give away if you can, is some of your weight (at least a few kilos).

Your social behaviour history (alcohol and smoking) and bad eating habits (sodas, takeout, fatty foods, sweets and processed foods) is the next card you should ditch. Don’t judge, look at you and slowly chip away at what you can improve on.

The card you must take is exercise (easier said than done) and healthy dietary choices (who gets that right all the time?). There is no perfect diet for anyone and maintaining a BMI under 30 is probably the most important diet goal.

Does this mean that you can let your hair down? The problem with doing a BRCA test if you’ve a family history, is that without an index positive (mom or aunty tested positive), a negative test means little because until our clever computers work out the AI algorithms for genetic codes, the combinations are like trying to open that safe. So many options, and no matter how you hold your stethoscope to the safe door, we can’t work out the many combinations that may affect your health.

A bit like a slot machine, the more genetic material we feed into the AI health systems, the more likely we get the genetic lotto combo that means lots of genetic moolah information that may help on how to modify your life. This is why having banks of genetic whole genome sequencing is of value. Remember you can’t prevent completely but you can decrease your disease profile risk by understanding where your genetic code provides possible chinks in your armour.

How does this genetic code lock work?

We all know I’m an anxious traveller so all the locks in my house have the same combination. Now that may sound like a daft and simple combination. But if you try and open a lock, the options are endless; 999 to be exact.

This explains why trying to uncover a single genetic mutation causing a breast cancer can be so difficult and daunting for a geneticist as there are so many combinations. Combination mutations occur when there are family histories on your father and mother’s side of breast cancer (particularly) and other cancers too. So, the cancers that may cluster together, creating a way for your family lock to open are breast, prostate, melanoma, stomach, colon, pancreas, and thyroid (certain types).

The issue is more about the age at which the family members developed the cancers and less about the number of cancers in family members. So, getting cancers when you’re young and your cells have had less chance to age and be exposed to all the environmental pollutants is more likely to be due to a genetic cell malfunction (one or many).

Now about that result, the geneticist says you have that gene. About 10-12% of women have a single gene mutation causing their breast cancer, and the percentage is higher in younger people who get breast cancer. The real truth is that you’ve had that gene since you were born, you just have more info now.

Genetics are worries that you’ve no control of. My kids look at me and ask what they can do to avoid being like me, and to an extent they can. Never underestimate the power of nurture. In the nature vs nurture argument, adapting your environment is critical.

Tempering your genetics

How do you avoid nature? You can’t, but you can temper it if you know your genetics. This is a plus, much like being aware of global warming and environmental pollutants, you need to take the same approach with your body.

If you have a family history of high cholesterol, you shouldn’t be smoking or overconsuming alcohol; you should be watching your diet and exercising regularly and ensuring that you’re not overweight. Same applies if you’ve a family history of hypertension. Guess what? The same applies if you’ve a genetic predisposition to cancer.

The one genetic anomaly that you have heard about are the BRCA 1 and 2 genes. These account for 6-8% of genetic mutations. There are a couple of other weird and wonderful ones. In patients with a personal and/or family history of breast and other cancers, a specific predisposing gene is identified in <30% of cases. Up to 25% of hereditary cases are due to a mutation in one of the few rarely identified genes with high penetrance which result in an 80% lifetime risk of developing breast cancer (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11).

An additional 2-3% of cases are due to rare mutations with moderate penetrance gene, associated with doubling the risk of developing cancer (CHEK2, BRIP1, ATM, and PALB2). 

Founder mutation

Some groups of people are more susceptible to the BRCA1 and BRCA2 mutation? The first step is to understand the concept of a founder mutation. A group of people who are usually historically from one isolated geographic area develop a genetic mutation. This is then seen more frequently in that group.

We have, for example, Afrikaner founder mutations for BRCA and Ashkenazi Jewish; one found in people from Scotland; and, basically, in other parts of the world, such as people of Eastern European descent and those from Iceland and Norway.

So, what are we saying? When we have a group of people from one specific area, it’s more likely that there will be certain genetic traits that come to the fore: more pure blood and less muggle.

Who should consider genetic testing?

Should all people test or only those with a family history of cancer, or those from parts of the world where more BRCA mutations are found? Personally, I’m pro genetic testing as it provides useful information as to how you can adapt your life.

Whilst there is no single definition of familial breast cancer, accepted criteria for testing are: at least three breast and/or ovarian cancer cases in a family; two breast cancer cases in close relatives, with at least a case diagnosed before age 50; two breast cancer cases in a family diagnosed before 40 years of age; any male breast cancer with a family history of ovarian cancer or early onset female breast cancer; Ashkenazi Jewish ancestry with breast cancer, particularly triple-negative breast cancer diagnosed before age 60; or breast and ovarian cancer in the same patient.

It’s important to understand what testing means and why; having an idea of family history or family history combined with certain backgrounds increases the chance of a positive test. Ideally, testing a person in your family with a cancer is better than a random test as a negative test doesn’t exclude mutations. This isn’t as simple as going to a lab and saying test me for BRCA, proper counselling by a genetic counsellor is required.

What if there are so many people with cancer in your family and you test for BRCA and it’s negative? Are you safe or did we get the lock combo wrong? Because life like that special meal is all about the combo of ingredients.

You have the gene, what next?

Not all people with a genetic mutation develop the disease. With BRCA, we talk about a 60-80% lifetime chance of developing breast cancer. So, how is it that you can have that naughty missing code and not actually get a cancer? How come the clever statisticians don’t say 100% of people with a BRCA gene mutation get a cancer?

Imagine this, a BRCA mutation is a seam that is missing in the sewing together of your genetic clothes. This can be for different types of breast cancer, with BRCA1 cancers occurring more commonly in younger women; more commonly triple-negative. BRCA 2 cancers more often occur at an older age; more commonly associated with men; and more commonly ER-sensitive.

But diseases, genes and people don’t follow textbook guidelines. Penetrance of the gene with a combination of person, lifestyle factors, genetics and other luck results in the breast cancer expression not necessary occurring, or presenting differently. 

The options

If a woman tests positive for the gene, what are all her options? Is a preventative mastectomy and/or oophorectomy always the best means of preventing cancer developing in the future and why or why not?

First is to understand that if you test positive for a gene, you’ve had that gene since you were born, and you shouldn’t rush into any treatment. It’s important to look at your family and which and what cancers they got when, to understand all possible cancers that you can get. Whereas you can cut off breasts and take out ovaries, the same can’t be said for your skin or pancreas.

Screening

Regular radiology and clinical screening is important. This includes ultrasounds twice yearly, mammography yearly from age 35, and yearly MRI scans.

Less than 20% of patients elect for risk-reducing surgery. This isn’t cosmetic surgery and comes with potential complications. It should always be discussed in detail, witha clear understanding of problems attached to any surgery.

We are saying the same thing

So, actually everyone is still saying the same thing: whether you’ve genetics for breast cancer or cholesterol, exercise and control your habits and weight.  Embrace understanding your genetic make-up that you can’t control but can temper. Be your own best friend, change what you can and don’t feel guilty for what you can’t. Enjoy the game, it’s all that you have and make the most of the cards you’re dealt.

Header image by Freepik