Me and My Mutation

[Editor's note: Like actress Angelina Jolie, up to 2,300 women in Canada may be diagnosed this year with the breast cancer genetic mutation. Many of these women are the third or fourth generation to have cancer in their family. Today on The Tyee, Kate Follington tells the story of her struggle over whether to pass her breast cancer mutation on to her children or find a medical way out.]

I'm the only person I know who pays an annual storage fee to safely preserve a group of embryos. There are eight of them in all, each three-days-and-eight-cells old, locked up in a giant freezer at a fertility clinic in Vancouver. I pay $200 dollars a year in rent.

It started as a simple case of self preservation.

In 2010, just before starting chemotherapy for a tumour I found in my left breast, I worried about losing my fertility. Someone recommended the freezing, so I convinced my partner at the time to help me create the embryos. With the help of a foundation that supports young cancer patients facing infertility, it didn't cost much. Four weeks to the start of treatment, we took the opportunity.

Despite an intense six months of chemo and a year of stalled menstrual cycles, including menopausal hot flashes that felt like my hair was on fire and my face was burning off, my ovaries eventually kicked back into gear, a year later. I assumed if I got pregnant, I would have children naturally.

During that time my partner and I lay in bed at night and occasionally talked about our frozen embryos. Smiling at the possible label on the petri dish -- "An interesting blend of ancient Andean fortitude, Japanese finesse and Australian spirit; they will be stocky, short, strong-willed and charismatic" -- we jokingly referred to them as our eight warriors. For the most part though, I thought of them distantly, a wonder of science we would likely never need. Even less so once my fertility returned.

Mid-treatment, however, my oncologist began to stress the need for further investigation of my genetic code. It's not typical, you see, to find a tumour in your breast at 33. She explained that tests would determine what course of treatment to prescribe and help explain what may have caused my body's inability to ward off tumour growth, given the fact I was fit and healthy at the time of diagnosis. My DNA went under the microscope.

Free spirits and free radicals

I'm the fourth woman in my family to be diagnosed with breast cancer, so it wasn't a huge stretch to assume something genetic was involved. My mother's two cousins died of cancer, while my mother herself, diagnosed at 40 and again at 50, is still standing despite two tumours in both breasts.

The DNA test threw back some distressing results: I carry a rare genetic mutation called BRCA2. My oncologist recommended a complete mastectomy and breast implants to reduce any chance of recurring cancer, which because of the mutation, was somewhat likely. I soon learned it would also conveniently reduce any future sagging problems; I now wake up everyday like I just stepped out of a cold pool.

Most cancers are linked to aging or lifestyle, not genetics or family history. Of the 22,700 women diagnosed with breast cancer in 2012, about five to 10 per cent of diagnoses are related to one of two genetic mutations.

In a normal, healthy genetic system, when something mutates within a gene structure the cells begin to implode and then die, destroyed by a pair of tumour suppressor genes which kick into action. To stop cancer forming, we need at least one of the pair of suppressors pulling its weight, constantly repairing damaged DNA.

In my case, one gene scrubs up and fixes damaged DNA (free radicals!), and if it sees cells dividing too much because they're damaged, it switches them off. However, the other gene is permanently sleeping in the corner. The good gene is then overwhelmed with all that "suppressor" action. That's how cancer cells spin into overdrive and tumours come knocking. Hence cancer at 33.

Mapping the trends of hereditary cancer is extraordinary -- so similar are the cases it's almost hard to believe. For example, families tend to display a younger diagnosis with each generation. A 2009 study from the University of Texas that looked at 132 families -- all mutation carriers with multiple generations of cancer patients -- revealed an average drop in age of seven years between successive generations. My mother was 40 on her first diagnosis; I discovered my lump two weeks after my 33rd birthday. Exactly seven years.

Studies have also found high rates of new primary tumours appearing within 10 years. My mother was diagnosed with a second tumour roughly 10 years after her first. At the time of that diagnosis, in 2000, genetic research and trend mapping was still in its infancy, so they couldn't have predicted what was in store for her future, nor mine.

These days, however, it's quite different; there are statistical probability rates for both breast cancer mutations BRCA1 and BRCA2. As it turned out, I had a 46 per cent chance of developing cancer from the day I was born and a 40 per cent chance of developing a second tumour within 10 years of the first. The same stats will apply to my daughter if she's carrying the mutation: a 46 to 57 per cent probability, and a more than 20 per cent chance of developing ovarian cancer.

It suddenly dawned on me one evening, late into the night, that if I had a daughter she could face a cancer diagnosis as early as her mid-20s. Seven years younger than my year of diagnosis places her at risk by her 26th birthday.

With this knowledge, I saw my eight frozen warrior mini-mes differently. They might all carry the BRCA2 mutation, some of them might, or they could be completely mutation free.

I wondered: If I could remove the mutated embryos and birth one without the bad gene, could I reduce my daughter's risk of cancer from almost 50 per cent to 12 per cent -- the same statistical chance of breast cancer as all women -- effectively eliminating the mutation from my family's genealogical DNA? And would I, given the choice?

Journey into the gene void

A bit about myself. A hippy at heart, I prefer and even revel in the natural chaos of things. In short, until Nov. 13, 2009, genetically modifying my children was not how I rolled. I would've loved them in whichever strange combination of bone and fur they were delivered. But I'm also a realist, and hard evidence was all around me in the form of medical charts, diagnosis sheets and memories of other young women I know who lived with cancer.

Women not as lucky as me. Women I shared meals with at health retreats for patients, women who sat next to me in the chemotherapy chair, who I compared breast scars with and then sobbed over when their cancer recurred and they passed away. Their shared spiritual insights and stories during their final months were life-changing, and not easily forgotten.

I spent a good part of six months reading scientific journal articles and learning every word from genome to ortholog in Wikipedia. I entered a world that shot me down a twisting ladder of DNA strands, spinning me in and out of genetics and bending my brain backwards visualizing a single microscopic cell, before zooming me past 30,000 genes like beads on a string that decorate our chromosomes only to arrive alongside chromosome 13 and BRCA2, the gene that doesn't work properly, the mutated gene, mirrored in every one of my trillions of cells.

Single gene mutation testing is already available for around two dozen (often more) of the most common disorders, including life-threatening diseases such as cystic fibrosis, Tay Sachs and Huntington's disease, as well as the more familiar syndromes like Downs, and more manageable though still life-affecting diseases like Celiac's. There are known genetic mutations linked to over 1,000 disorders and gene testing is advancing at a rapid rate. Medical termination is an option if the breast cancer mutations, BRCA1 and 2, are tested positive in the womb, however requests for this are rare, as there's no guarantee of adult on-set diagnosis.

My brother chose to let nature decide his daughter Lily's future by not testing either himself or her, and there's something to say for letting fate work its magic. I respect my brother's decision; after all, many memorable days of my life weren't necessarily good for my health. Had I known, as I do now, that I have a mutation that makes me vulnerable to cancer, I might not have so hedonistically indulged in the past. Or perhaps I would have revelled in it longer! And different life opportunities may have presented themselves.

Future of gene repair

The question, then, was is it medically possible to test for the mutation on a frozen embryo eight cells in diameter?

My doctor responded by email: My embryologist Jill spoke with an embryologist at RMA (Reproductive Medicine Associates) in New Jersey. I also spoke with Dr. Richard Scott on Thursday at a meeting in Chicago. They are probably the only clinic world-wide that could accommodate your request. You will need to set up a phone consultation and we will forward your chart and a note from me to explain. Let me know what you would like. JR (Dr. Jeff Roberts, Pacific Centre for Reproductive Medicine, Vancouver)

Parents will move mountains for their children, but unlike driving them to the other side of the city for baseball, I considered meddling with their genetic structure, their magnetic plate, before even the first seed had begun to shoot. At times this seemed a bit extreme; like a sci-fi novel, I proposed hand-picking the DNA of an eight-celled being whose life experience so far has been to multiply and freeze. But logically, by removing the mutation carriers from the eight, my hypothetical children, once implanted, would have the same chances of getting breast cancer as other "normal" people -- no more, no less.

I was asked to send my embryologist reports to specialty clinics in Australia and New Jersey for analysis, to see what options they had for testing the frozen embryos.

"We do offer PGD (pre-implantation genetic diagnosis) testing on frozen embryos, however the key thing here will be to find out if the embryos have been fertilized by ICSI (careful insertion of a single sperm into an egg, as opposed to blasting the egg with thousands of sperm). We won't be able to test them otherwise. Also, it is very important to know at what stage the embryos were frozen (day 2 or 3 or 5/6). There could be some loss on thawing the embryos but it is highly likely that there would be something to test from eight embryos, depending on the quality." - Public liaison Officer, IVF Australia.

Both clinics in New Jersey and in Australia required my embryology reports, so I sent them through.

Friends, on the other hand, were puzzled when I explained my fears for the little warriors. Free of the stats and medical history, it seemed excessive to them. Too many unknowns.

"We're talking about 25 years from now! Technology could be wowing us with repairing mutated genes," said a very rational journalist. So I asked my genetic counsellor, Carol Cremin, and my oncologist, Karen Gelman, exactly that question: Where will gene repair technology be in 25 years?

"Treatment options will be better: Better earlier detection, better combination drugs to assist in limiting tumor growth, and a better understanding of how to assist the mutated gene in doing its job," Gelman told me.

Fixing the lazy gene altogether however, as Cremin explained, is not that simple or even plausible. Some areas of gene therapy are showing promise, such as producing a virus to go in and repair damaged DNA. But science has not yet figured out a way to deliver a good copy of the gene to all of the specific areas of the body that need it.

My nurse friend Heather, who is not comfortable with any tampering or testing of embryos, argued that to remove embryos because they have the mutated gene either by aborting or through testing them as embryos assumes that other problems wouldn't cross their path.

I understood her point of view. We all face challenges in our lives; genetic mutation or not, my children will be as fragile as anyone and will face their own share of life's challenges, if not cancer then perhaps anorexia, depression or addiction. Was I avoiding one risk only to have selected an embryo that's vulnerable to something else, perhaps even another form of cancer?

In truth, my offspring may carry the mutated gene, but might live their whole lives with no signs of cancer at all.

In the case of Huntington's Disease, an incurable neurodegenerative disorder, every mutation carrier displays symptoms by their mid-40s, and they often don't survive beyond 20 years of the first signs of diagnosis. If my daughter is diagnosed with cancer as a young adult (a 46 per cent probability), and she finds a tumour early enough, she will also likely survive.

Logically I knew this. But as survivable as this horrendous journey of cancer has been for me, touch wood, knowing and loving some women my age diagnosed too late, some carriers of the same mutation, changed everything. Humbled at their courage in dying as they left behind small children, accepting half the life they expected, is confirmation enough that medical science simply can't solve all our problems.

What we can control

Including this one, it seemed. After months of waiting for a response from embryologists, all the while answering questions about the warriors, how they'd been formed, how many days old and number of cells they were, I received the same answer from Australia and New Jersey.

"Dr. Scott unfortunately has confirmed that because your embryos were formed by an [in vitro fertilization] process, and not ICSI, they are unable to perform the pre-implantation genetic diagnosis on the frozen embryos. We're very sorry to pass this news on. We wish you all the best in your journey toward having children."

It turned out the decision was not mine to make in the first place. Testing the embryos was clinically impossible because of the way they were frozen.

I'm now left with three options: selectively test in the womb for the mutation and abort, have the child with the mutation, or have no children at all.

Most parents have the same instincts: do the best they can to prepare their children for the risks they'll undoubtedly take, and hope like hell their stumbling blocks are survivable.

What we can control is the ability to celebrate every single obstacle they defeat.

At least, that's the lesson of my mutation.