It’s Rare Disease Week, and this year I’m thinking about it in a new way.
My experience with breast cancer has been so different from the diagnostic odysseys that rare disease families traverse. While they’ve championed novel treatments where none existed, I had choices handed to me, the protocols detailed and time-tested, with instant support from thousands of “pink sisters.”
A rare disease affects fewer than 200,000 people in the US (1 in 1,615), or fewer than 1 in 2,000 in Europe. Parents are told their children are one in 50,000; one in a million; one of a handful of patients known in the world. Or the only one.
That was the case for teen Vincent Pieterse, whom I wrote about in April, 2015, in the Journal of the American Medical Association, “Exome Sequencing Comes to the Clinic.”
At the time, he was the only person known to have what’s now called brachycephaly, trichomegaly, and developmental delay. But in September 2015, Vincent’s dad, Marc, using the tool Genematcher, found a 5-year-old who has it. (See this article about the controversy over the condition’s name.)
In contrast, breast cancer is everywhere. In the US, 3.1 million women have had breast cancer (I hate “survivor,” I’m not outracing a tsunami); 1 in 8 women develop it at some point in their lives. (I also hate “contract” cancer; it isn’t an infection.)
Comparing a cancer to a single-gene disease is somewhat apples to oranges, but during rare disease week I can’t help but think about how the medical journey differs.
When symptoms unfold gradually, diagnosis can careen from one explanation to another. For Taylor King, fading vision at first looked like retinitis pigmentosa. But then difficulty with arithmetic in second grade and other findings led to an unexpectedly dire diagnosis: a form of neuronal ceroid lipofuscinosis, aka Batten disease.
For Hannah Sames, the first sign of giant axonal neuropathy (GAN), recognizable only in retrospect, was her kinky hair at birth, so different from that of her sisters and parents. Her grandmother noted the toddler’s halting, hesitant steps, and by age 3 Hannah’s legs bowed. But physicians dismissed the observations until a physical therapist friend viewing cell phone video recognized a gait reminiscent of muscular dystrophy. Finally, an astute pediatric neurologist connected the diagnostic dots, retrieved a textbook and opened to a page featuring a child with crazily kinky hair. The boy had GAN.
But I had no symptoms, no lump, although my mother had been diagnosed with breast cancer at my age. All I had was a bad mammogram – a routine test that millions of women take each year. I’d been called back for a repeat test before, so no worries.
Not this time. Following the second, diagnostic-level scan, events unspooled quickly, dancing to a choreography set by health insurance coverage. Biopsy. MRI. Diagnosis: ductal carcinoma in situ (DCIS).
Next: My DNA would reveal whether I needed a single or double mastectomy and to alert relatives.
For Taylor, an enzyme deficiency narrowed the pool of genetic tests to the 8 types of Batten disease, which affect 2 to 4 newborns per 100,000 in the US; her mutation is in the gene CLN1. Taylor’s family has raised funds for an upcoming clinical trial for a gene therapy. Her sister Laura tells the story in a TEDx talk and in her book, Run To the Light, due out in November.
Hannah had just turned four when genetic testing confirmed the pediatric neurologist’s clinical diagnosis. Back in 2008 only a few dozen people in the world were known to have GAN. Thanks to her parents’ efforts, that number has grown, but not by much. Still a unicorn among the zebras of rare diseases, GAN may be misdiagnosed as a form of Charcot-Marie-Tooth disease.
Today diagnostic odysseys are shortening thanks to clinical exome and genome sequencing of children sick enough to be in intensive care units. Here is one child’s story. But those technologies wouldn’t have helped Taylor or Hannah, whose symptoms appeared slowly.
Genetic testing was much easier for me.
Single gene tests or neurological disease test panels can detect Batten disease or GAN, typically ordered by a pediatric neurologist. But a BRCA test? Thanks partly to celebrity spokeswomen like Angelina Jolie and Sheryl Crow, BRCA breast cancer susceptibility tests are familiar.
I chose a test panel from Invitae that covered more than 80 oncogenes and tumor suppressor genes, and had results in about 10 days. I have nary a mutation, so a single mastectomy was ok and my daughters and sister had no elevated risk from those genes, which I blogged about a few weeks ago. (My insurance wouldn’t cover my test. I suspect it’s because the powers-that-be don’t understand that many genes hike breast cancer risk, not just the BRCAs.)
But DNA tests are only the first step in the molecular interrogation of cancer.
If breast cancer cells are festooned with extra estrogen or progesterone receptors, then drugs to block these hormones, like Tamoxifen, are needed. The idea to do this dates to 1973 by some accounts, but also to farmers’ observations on lactating barnyard animals in 1896!
If breast cancer cells sport too many human epidermal growth factor receptors, then the drug Herceptin can help.
But there’s still more!
Oncotype DX is a gene expression profiling test that I wrote about in 2003, when it was introduced. “Oncotype” is now bandied about on Facebook as commonly as “mastectomy.” The score indicates how likely chemo is to work. It’s exciting to see something that was once a research tool alter lives.
Anatomy provides clues too. Tumors are graded by how often their cells divide, number of lymph nodes involved, and where they are and aren’t. A breast cancer shorthand pervades online posts, as much a part of the lexicon as LOL or FOMO: “IDC, Left, 2cm, Stage IIB, Grade 2, 1/2 nodes, ER+/PR+, HER2-,” reads one.
TMI? No! With any disease, the more information the better. And with so many tests, options, and classifications, breast cancer may be common, but treatment highly tailored.
Batten disease and GAN have no FDA-approved treatments. Hannah’s had gene therapy and is working hard as her motor neurons begin to manufacture the protein that her body cannot naturally make. But gene therapy will come too late for Taylor.
In contrast, treatment choices and protocols for breast cancer are so varied that the barrage of information can be overwhelming when you’re going through it – I can see why many women simply listen to whatever their doctors say. It’s comforting to know that something can be done, for a long time. Even women with stage IV breast cancer can live for many years.
Communication and Support
Taylor’s family started Taylor’s Tale and Hannah’s family started Hannah’s Hope. Communities coalesce, fundraising and awareness campaigns begin, and, ultimately, research leads to treatments. It’s happening right now, for many rare diseases. (See Talia’s Story, my Rare Disease Day post from last year.)
Umbrella organizations unite the rare disease patient group silos, to share stories, resources, contacts, ideas, tips, and solutions. These include the National Organization for Rare Disorders, Global Genes, Orphanet, and CheckOrphan.
In contrast to the years it took Taylor’s Tale and Hannah’s Hope to build their groups, it took me mere minutes to find help.
Googling got me right to www.breastcancer.org message boards, where it seemed every conceivable question had already been asked and answered many times.
On Facebook I joined more than 15,000 women in three closed groups. The 12,475 members of Breast Cancer Straight Talk include the newly-diagnosed and those recovering and in treatment; discussion ranges from technical details to dealing with stupid comments and fleeing boyfriends to images of foobs (fake boobs). The 2,804 women in Breast Cancer and Fitness are feeling better.
I’m one of only 116 members of the High Grade Negative DCIS Support Group, where last week I found a link to a paper in Cell that I doubt even my oncologist has read yet. The findings are surprising – that DCIS doesn’t differ genetically from invasive ductal carcinoma – and confirmed that I’d made the right choice of mastectomy over lumpectomy.
Information is empowering, no matter how rare or common a disease. It quells the terror, identifies the enemy. I hope that continuing annotation of millions of human genomes will enable those with rare diseases to soon have as many options as I have had on my journey.