Fighting cancer one question mark at a time

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The morning after I discovered the hard, round mass far down the side of my left breast, I arrived unannounced at my doctor's office. The lump was small but it was there, and I needed my doctor to give a reasonable explanation for its appearance. After an hour in her office, I left with assurances and appointments for a follow-up ultrasound and MRI, and with the beginning of a cold certainty that cancer had caught up with me. This hard little pea, as I'd come to think of the mass in the hours since I'd found it, had rolled down through my family: from my grandmother, to my father and now to me.

It was February, 2008, and I would learn a week later, after the tests and scans rapidly moved this discovery from concerning to urgent, that it was invasive-ductal carcinoma. Or, as a wonderful medical fellow from New Zealand would soon explain to me with a warm smile on his face, "your garden variety breast cancer."

I was 39. A mother of three children. A woman who ran a business she loved. When I got the call from my doctor confirming the diagnosis, the floor tilted wildly, and a lot of things must have gone through my terrified mind, but "Why me?" wasn't one of them. In fact, something quietly slipped into place, like a knot cinching on a thin cord. "Why not me?" was more to the point.

My two sisters and I had by this time been in rigorous screening for breast cancer for several years – ever since my father was diagnosed with intra-ductal carcinoma and underwent a mastectomy on his left breast. Male breast cancer is rare, accounting for only about 1 per cent of all breast cancers. What made my father's situation all the more concerning is that his mother died of metastasized breast cancer when she was just 34, leaving behind her only child, a 21-one-month-old baby. We had grown up with the tragic story of my grandmother's early death; my father's diagnosis cast it – and the question of what might be lurking in our genes – in a new, sharper light.

My father's doctors believed he was probably carrying one of two recently discovered genetic mutations for breast cancer – BRCA1 and BRCA2 – and suggested genetic testing. With three daughters, my dad felt an urgent need to know what dangers lay ahead for us. Cancer seemed to be circling my family: my sister had Hodgkins lymphoma when she was 18, and, though we didn't know it yet, my father would within three years also be diagnosed with prostate and skin cancer. Could a blood sample and some DNA analysis solve the mystery of why we seemed predisposed to cancer? At that point we could only hope.

We didn't know how we'd cope with knowing the results of my father's genetic test – how would we feel knowing we had a mutation that drastically increased our risks for breast cancer? Would it leave us with a sense of being more protected or more vulnerable?

In the end, the results brought more uncertainty: My father didn't have the mutation, and we were left wondering whether that news was reassuring, or simply evidence that science didn't yet know what was causing my family's cancer.

But our brains have a way of protecting us from fear, especially abject, undefined fear like the risk of something like cancer. And I felt wrapped in a protective shield, cushioned from threat by some sort of vague law of probability: Cancer had chosen my sister and father, not me. I wasn't going to get sick.

My daughter was 16, my sons, 7 and 2, when I got my diagnosis. The conversations I had with my daughter around the realities of what was happening were filled with facts and reassurances, optimistic statistics and medical information. When I spoke to my sons, I told them about this strange thing the doctors had found in my breast. Like a pea, it was growing there quietly. But if I left it alone, it would continue to grow and could eventually make me sick. We all decided that the best thing to do was take the pea out, take some medicine and be done. And that's what I did. Like standing at the opening of a long, dark tunnel, I put my head down and blasted through as fast as I could to reach the light and air at the other end. Over the course of the next 11 months, I underwent a lumpectomy, four rounds of chemotherapy, a double mastectomy with reconstruction, and a laparoscopic salpingo oophorectomy (removal of my ovaries and fallopian tubes, because I now worried about ovarian cancer, sometimes linked to breast cancer).

While I was recovering from the mastectomy, one of my sisters confided that she'd found a lump in her right breast. "There's no way…" we both said. But she didn't have the luxury of denial and within a week, she had her own diagnosis: more garden-variety breast cancer. When I was diagnosed, and then later when my sister was, the doctors spoke again of the likelihood of finding a genetic marker. They assured us that the process had become more sophisticated and refined since my father was tested. And so they took blood samples and scrutinized our DNA. And still found nothing.

During the years since, my family's relationship to breast cancer has continued to puzzle doctors. I imagine we, like other families with multiple cases of breast cancer who don't present any of the known genetic mutations, have been thrown into a file with a big question mark attached. Something is clearly going on deep within our shared DNA; no one could possibly say this was a coincidence. The question shouting from the silence of quiet moments was what was happening at a genetic level to make us such a fertile ground for cancer?

By the summer of 2011, it looked as if we might finally have a chance to find out. Steven Narod, Canada Research Chair on Breast Cancer and a professor at the Dalla Lana School of Public Health at the University of Toronto, was looking for a family with an unusual cancer history. A member of the international research teams that uncovered the BRCA1 and BRCA2 mutations in the 1990s, Dr. Narod remains at the forefront of efforts to decode the intricate relationship between genetics and cancer. In Canada, he seems to be the end of the road for families like ours – patients who present disturbing patterns and frequency of breast cancer that cannot be explained by known mutations.

Dr. Narod now had funding to map the entire genome of a family and scrutinize it for irregularities and mutations in an effort to uncover something new. He chose us. All he needed from us was a complete family history and blood samples. A a lab in Montreal would decode our DNA and he and his team would analyze it.

"This is good as it gets," Dr. Narod told me when I met him to discuss the results in his office at Toronto's Women's College Hospital in late November. I think he was talking about my family – as research subjects, we offered a rich vein of information – but I also knew that whole-genome sequencing was about as good as things got, from a genetic research standpoint.

I had come to the meeting ready to hear that they'd found something to account for the breast cancer in our family; a marker of some sort that we would eventually be able to use to test my other sister, who was in rigorous screening and operating under the assumption she had a huge bull's eye on her chest, and our children. So I was completely unprepared when he told me they'd run the analysis, and found nothing. "The possibility that these cancers are due to chance is zero," he said. "We think there's a gene there and not one we've seen before." The challenge is in finding it.

The typical genome has about 20,000 variants, most are normal and define what make us unique (green eyes as opposed to blue, being taller than someone else in your family). But Dr. Narod and his team are looking for more harmful mutations. At this point, they've narrowed the field from 20,000 to 210. They are going to keep looking.

Sitting in Dr. Narod's office, I realized how profoundly disappointed I was that they had not yet found something. I had, without ever really thinking about it, let myself hope that this research would provide absolute answers. But another thought struck me, as well. I was in the same position my father had been 15 years earlier. I had faced the worst in finding my own cancer, but new information could highlight new risks for my family: my kids, the three people I loved most in the world. My sister and her daughter. My mind turned to the question the genetic counsellors had asked us: What was I prepared to do with this information?

I don't have any answers for this. Not yet. But I have agreed to Dr. Narod's request that I meet him and his team of researchers in their lab in January, to participate in discussions that will lead to a more targeted analysis of our DNA. I know more now, and understand we still may not find what Dr. Narod believes is certainly there. But knowledge and time are the only things that make a difference in staying ahead of the devastating course of cancer. I want to take control of both. And maybe, just maybe, I'll begin to fill in some of the dark spaces of my cancer, shedding just a little bit of light on what we don't know. And sharing that light with others.