My sister, Bea, was 35 years old when she was diagnosed with breast cancer, and 38 years old when she died in 1993. She left behind a husband, two toddlers and, innocently, a genetic legacy that our family continues to confront today.
While she was alive, Bea participated in a clinical study run by a prominent research institution, the goal of which was to discover gene mutations that predispose individuals to cancer. The rest of our family – my mother and father, my two brothers and myself – also agreed to participate.
The consent forms each of us signed indicated that the institution would be in touch if they learned anything. As a physician still in training, I was happy to be part of a clinical study. And because we’d heard little from the researchers in the years following Bea’s death, I was even happier to take their silence as a good sign.
As it turns out, my interpretation of their limited communication was based on hopes rather than facts. As Stephen Colbert would so often say on “The Colbert Report”: “Truthiness prevailed.” Eventually, I’d find myself on a twisted road toward reality.
Nine years to the day after Bea died, I finally did call the research institution to confirm that everything was A-OK. In the time since Bea’s death, I’d embarked on a career as an oncologist-scientist and was poised to become engaged to my now-husband, Sean. I hoped that this phone call could lay to rest any lingering cancer-risk concerns and, in turn, allow me to marry free of worry.
Up until then, I had had reasons to wonder about my family’s genetic inheritance. Not only had Bea succumbed to cancer at a young age, but my father’s branch of the family tree was permeated with the disease. So, naturally, I was surprised when the person I spoke with told me that my family’s experience with cancer was “not clearly hereditary.”
I asked if he was sure, and he affirmed that they had no evidence for a genetic cause for our family’s cancers but that they would inform us if things changed.
“Excellent!” I said. Now I could move on, marry the perfect guy and start a family. I was eager to hang up and get on with life since I no longer had to fear that a cancer-causing gene was targeting my family like a serial killer. Bea’s early death was simply an unfortunate fluke.
In the mid-1990s, a few years after Bea’s death and during my internal medicine residency and oncology fellowship, scientists discovered BRCA1 and BRCA2, the two genes most commonly linked to hereditary breast cancer (and other cancers). A few years later, new clinical data indicated that surgical removal of normal breasts and ovaries reduced the risk of breast and ovarian cancer in women with BRCA mutations. If Bea had one of those mutations, I thought, would prophylactic surgeries have prevented her premature death? Certainly, if she did have a mutation, then we would have heard from the research institution by now. In any case, these discoveries fueled my enthusiasm for studying cancer-causing genes.
Of course, given how long it took me to follow up on my family’s clinical study, my passion for cancer-gene hunting could not have extended too far into my personal life. As a doctor, I knew this information could help my family make key health decisions, but as a person about to tie the knot and a junior scientist setting up a lab, I was too busy, too immortal. Objectivity was overshadowed by denial, and the research institution’s “not clearly hereditary” phrase gave me permission to start a new chapter without caution.
Consideration of a possible cancer predisposition was postponed until further notice.
The vagueness of the phrase “not clearly hereditary” enabled my “truthiness.”
This state of denial ended in September 2003. At Sean’s urging, I asked a friend who is a dermatologist to check out a spot that had appeared on my calf a year earlier. Our friend, being unsure of what it was, offered to remove and test it.
A few days after the biopsy, I listened to a voice mail from a dermatology fellow while I was driving home that indicated we needed to talk. I turned the car around and drove back to the office. My heart was pounding in my ears as I went online to check the pathology record, which indicated the spot was a thin melanoma. No problem. This could be easily treated with a minor surgery. So why was my heart so revved up?
After surgery a few weeks later, I was relieved to be free of disease but also slightly embarrassed that I hadn’t bothered to investigate the melanoma sooner. Denial was starting to fade, and I realized that I could no longer ignore reality. Sean pushed for us to obtain a second opinion about my family’s genetic predisposition to cancer.
In January 2004, we took a memorable drive from Ann Arbor, Michigan, to a well-known cancer genetics clinic in Columbus, Ohio. After an assessment, the oncologist and genetic counselor said that with my dad’s Ashkenazi Jewish background, our family history of cancer and my melanoma, we could first test to see whether I carried a BRCA mutation. We had an extensive counseling session, a blood sample was collected, and Sean and I departed, expecting a six-week respite.
Four weeks later, we received the call. I had tested positive for a BRCA1 mutation. I thought I’d be agitated by the news, but instead I was excited to be given concrete information, excited to have surgical options to reduce my risk and excited to tell my family.
During one of our routine Sunday dinners with my mom – an economist and Russian scholar who was then 82 – Sean and I tried to describe the results, but they just didn’t compute for her. She was convinced that the gene had come from her Polish-Catholic side of the family, despite our careful explanation that the mutation was common in Ashkenazi Jews and had almost certainly come from her late Jewish husband, who had had several cancers by the time of his death. It was remarkable how difficult it was for her to grasp the genetics. She remained adamant that the mutation had come from her; we remained convinced that it had come from Dad.
In the middle of this debate, she said, “You know, Bea’s research institution sent me a letter some time ago saying they had new information.”
“Did you call them to find out what it was?” I asked.
“No, I forgot about it and filed it away. But it must not have been important, or they’d have contacted me again.” She brushed it off, but we weren’t so sure.
Sean asked my mother to retrieve the letter from her files. Dated two years earlier in 2002, it was an innocuous, vague form letter that simply said the center had new information and for a small fee she could receive the result. It rang no warning bells that the information might change the way she and her family members managed their cancer risk. I would have filed it away, too. But with my recent BRCA1 test results, the letter held more significance.
The next day, I called the institution, explained the situation and asked about the new information. The staff checked their files and apologized profusely for not following up. They had, indeed, discovered the BRCA1 mutation in our family. I urged them to send me all information they had on our family and hung up the phone in disbelief.
Stunned, we wondered whether anything would have changed had we known sooner. If I was housing any breast or ovarian cancer now, would I have had it earlier? Had similar oversights happened to other families?
(I chose to have prophylactic mastectomies and oophorectomies, and I was lucky to learn that, despite the delay, I did not have breast or ovarian cancer.)
The shock didn’t end there. As I pored over the data they sent me, it became clear that the researchers had not tested my father for the mutation. My mother had been right: The positive test had come from her. It made little sense, but facts were facts. We began notifying our maternal relatives, knowing it was still possible there was another mutation on Dad’s side.
Although it was too late for Bea, those of us in the family with the mutation now have the opportunity to manage our cancer risks in ways she never had.
There’s no doubt that when the research institution identified the mutation in my mother, it should have contacted family members who had consented to participate. But it was also my reliance on “truthiness” that prevented me from being proactive and communicating regularly with the institution.
I had risked my own life because I had preferred to stay blissfully uninformed for so long. I made the deadline thanks only to a great partner, great luck and great genetic care. Others may miss the deadline due to bad luck and, more often than not, absence of genetic care.
If I, a doctor who lost a 38-year-old sister to cancer, could avoid seeking out the data, it’s easy to see how others could do the same. At times, we all need the relief of “truthiness.” But when it comes to most health decisions, knowing is better than not knowing. Knowledge allows for choices, choices that can improve and save lives.
Ross, author of ” A Cancer in the Family: Take Control of Your Genetic Inheritance,” is an oncologist and director of the cancer genetics program at the University of Texas Southwestern Medical Center.