by Lizzie Stark
As a BRCA mutation carrier, my risk of ovarian cancer is also elevated. How high? As with all the BRCA risk numbers, research is still coming in, and they’re being revised, largely downward, as the families used to discover the genes typically had very penetrant genes, while many mutations we now know about may actually connote a more modest level of risk. A study of Ashkenazi Jewish mutations says the lifetime risk is 54 percent and 23 percent for BRCA1 and BRCA2 mutations, respectively. But my mutation is French and hasn’t been widely studied. Another study of multiple families puts the lifetime risk at 39 percent and 11 percent for BRCA1 and BRCA2 families. A third meta-study says it’s 55 percent for BRCA1 and 21 percent for BRCA2 carriers on average.
Thirty-nine percent, 55 percent for a BRCA1 mutation, what’s the difference, really? No matter what way you slice it, that’s a drastic, exponential increase over the typical woman’s lifetime risk, which is about 1 in 72 or 1.4 percent. And the disease is a killer. Even though it’s only the eighth most common cancer in women, it is the fifth leading cause of cancer-related death in women. When caught early, it’s mostly curable. The problem is that only about 20 percent of ovarian cancer is detected early, according to the American Cancer Society. And the likelihood of a woman living for five years after being diagnosed with ovarian cancer is only 44 percent, a rate that has only budged by about 7 percentage points since the late 1970s. Let me say that again: an ovarian cancer diagnosis means your odds of living five more years are worse than winning a coin toss. It feels extraordinary to me that my grandmother survived the disease.
The symptoms are a hypochondriac’s wet dream: bloating or feeling full, abdominal pressure or pain, pelvic pain, indigestion, constipation or peeing too much, losing your appetite or feeling full quickly, weight gain or loss, fatigue, lower back pain, nausea and heartburn, loss of energy, pain during sex, and spotting between periods. Maybe it’s food poisoning, or maybe it’s ovarian cancer. Maybe you’ve been partying too much, or maybe it’s ovarian cancer. Could you be pregnant, or do you have ovarian cancer?
As it turns out, I’m not so Heffalumpless after all. In no time flat I’ve transferred my anxiety from breast to ovarian cancer. My period changes, and every time I menstruate for the next year, I’m thinking about my ovaries. At my age, it’s vastly unlikely. Even in my family, women like my grandmother and her sister didn’t get the disease until their fifties, but for a while, it still feels like it’s the explanation for everything. I stub my toe. “Ovarian cancer!” I tell George. He gets a headache. “Ovarian cancer!” we shout together. We blame it for our over-seared beef, our messy house, my still-weak arm muscles.
A few months after my surgery, we grab a beer with an old friend who is now in medical school and meet his soon-to-be fiancée, an ob-gyn. I ask her whether people bug her for medical advice, and with an apologetic look in her eye, she tells me that usually, it happens in a situation like this, with a woman she’s just met who is a friend of a friend, or the girlfriend of a friend, who, when the night comes to an end, confesses some lady-business problem. Two beers later, I’ve got my serious face on and am telling her it’s probably ovarian cancer. It’s not ovarian cancer, she says, it’s not.
I hate feeling like a hypochondriac. As before, with the breasts I no longer have, I need reassurance that I don’t have cancer, the constant call and response asserting that I don’t have ovarian cancer now … or now … or now. Unfortunately, this is something medicine is not equipped to provide. To reduce your risk of ovarian cancer, you can do things like take oral contraceptives for a few years—check!—exercise—check!—be shorter than five foot eight—check!—and have children early—er … maybe? Of course, surgery to remove the ovaries or uterus or to close the fallopian tubes helps too, but that is dramatic to contemplate, leaving me again considering surveillance.
Like many other cancers of the internal organs, ovarian cancer is difficult to detect. The National Comprehensive Cancer Network (NCCN), a “not-for-profit alliance of 25 of the world’s leading cancer centers,” including participants from Stanford, Duke, Mass General, and Sloan Kettering, according to its website, recommends that BRCA carriers be screened for ovarian cancer every six months, using a transvaginal ultrasound to scan for masses and a CA-125 blood test, which looks for a certain substance in the blood produced by some ovarian cancers. Of course, as these guidelines admit, neither of those tools has been shown to be effective. Dr. Mary Daly is well aware of this fact. “We have a lot of data that there is no screening that works for ovarian cancer,” she tells me. Daly is the chair of clinical genetics at Fox Chase Cancer Center in Philadelphia and chair of the NCCN’s Guidelines panel on genetic/familial high-risk assessment for breast and ovarian cancer.
If ovarian screening doesn’t work, I ask her, why is it recommended? Mainly because the research isn’t in yet, she tells me. There are studies looking at whether taking CA-125 levels every six months, rather than every year, works better. “Frankly,” she tells me, “I’m guessing those won’t be successful either.” This is why it is important to get high-risk women into studies looking at cancer screening, so that the data improves. And then, there is the psychological angle as well. “Some women just have to be doing something because otherwise they feel helpless about their ovarian cancer risk,” she tells me. I have the sudden sense that the helplessness is not only frustrating to patients but to the doctors who want to help them as well.
Still, hope abides in the form of new research. If absolute CA-125 levels don’t work as ovarian cancer screening tools, maybe more individualized ones might. A recent eleven-year study of 4,051 women used CA-125 levels differently—tracing how a woman’s levels rose and fell compared to her own baseline over time. The study used the data to class 117 women into a high-risk group and gave that group transvaginal ultrasounds, which led to ten surgical operations. Of those ten surgeries, doctors found four cases of ovarian cancer—caught in early stages—two borderline cases, one case of endometrial cancer, and three benign tumors. Those are promising results but ones that are not yet conclusive. In the UK, a large-scale random screening trial of two hundred thousand women is being organized, and the results are due in 2015, according to MD Anderson Cancer Center, which performed the initial study. And that’s not the only research out there, of course. Dr. Daly’s group is also participating in research looking at new markers for ovarian cancer, in addition to CA-125. “So it’s kind of muddy waters right now,” she tells me, “but in one or two years we should have the results of this trial.” I hope that both of them pan out.
In the meantime, the only thing I can do is check the last items off my ovarian cancer risk reduction list, which means carving out more organs to satiate my ravening Heffalump.
I don’t feel as sentimental about my ovaries as I do about my breasts. They mean about the same to me as my spleen does—something I’d prefer to keep in, but not something that hits close to the core of who I am. That is, until I begin reading about the effects of oophorectomy. The procedure itself is far easier than what I’ve already gone through; it’s usually performed using tiny incisions. One BRCA carrier told me, “Mine went in through my navel. No scars. And compared to a mastectomy, it’s like going to the dentist.”
The effects of ovarian removal, though, affect a patient long past the recovery time. Oophorectomy removes the body’s main sources of estrogen and will give me instant surgical menopause, ideally, if I follow NCCN’s recommendations, between the ages of thirty-five and forty, or individualized based on my family history. On a cosmetic level, as fellow BRCA1 mutant, book author, and journalist Masha Gessen wrote in Slate while contemplating her own surgeries in 2004, estrogen in women produces most of the physical features we associate with femininity—a narrow waist, wide hips, skin that is less red than men’s, full lips, and lush hair. “Without her ovaries, a woman will often gain weight, especially around the midsection (there goes the torso), her skin will lose elasticity, her lips will lose their fullness and color,
and her hair will thin (though not necessarily the same way a man’s hair does). Another sexual attribute that goes out with the hormones is the libido.” Removing my breasts impacted my self-image because they were part of my femininity. It feels vain and shallow to say so, but removing my ovaries feels like it will take whatever’s left.
Surgical menopause does all the other things that natural menopause does and comes with risks of changes in sex drive, hot flashes, vaginal dryness, osteoporosis, and mental side effects such as loss of memory and decline in thinking skills. With natural menopause, which occurs, on average, around age fifty-one, the hormones ramp down over time, like a smoker who tries to cut down and then quit. Surgical menopause is more like going cold turkey. One day you wake up, and no more estrogen. Hormone replacement therapy can help mitigate some of the side effects, and I’ll be able to have that, I hope, because I’ve already had a mastectomy.
And then there are the more serious side effects of early oophorectomy, the ones that are still being studied. Some studies have found links between oophorectomy before age forty-five and things like dementia, cognitive impairment, cardiovascular disease, and, most shockingly, premature death. Of course, it appears that the science is still coming in both on possible links and on whether hormone replacement therapy affects these risks—for example, one model predicted that for BRCA1 and 2 carriers, oophorectomy would increase life expectancy by some years, regardless of the use of hormone therapy. For her part, Daly suspects the premature death risk is due to the risk of developing metabolic syndrome after surgical menopause, a condition characterized by an increased risk for high blood pressure, diabetes, abdominal obesity, and high levels of fat in the blood. She tells me surgical menopause raises a woman’s risk for metabolic syndrome from something like 20 percent to 30 percent. “Until recently, it wasn’t really recognized that this is something you have to be aware of and start screening for a bit earlier,” she tells me. But now, she says, “it makes sense to start screening these women who have early menopause whether BRCA-related or for other reasons.” This means watching glucose and blood pressure levels and weight. “These are all things we can control,” she reminds me, “unlike ovarian cancer that we can’t control.”
When I read over the list of possible symptoms of preventive ovarian removal, I can’t help but feel disappointed and angry at science. The only way to lower my risk is to give up my sexual drive, my waistline, even the thickness of my hair? It feels like the quest to reduce my risk could destroy everything I like about myself. As a writer, the idea of cognitive changes fills me with fear and dread the most out of all of the possible side effects. I rely on my ability to remember things, process complex thoughts, and render them back in prose. That ability touches the core of my identity. As I told myself over and over again as a teenager, if I can’t be beautiful, fine. I’d rather be smart and interesting. And what about my sexual desire? What if I lose my lust for my husband so early? That wouldn’t be fair to him, and it wouldn’t be fair to me either. It could change our relationship all over again, when all I want is for things to stay still and constant, to get a grip on what I have before I lose it again.
Sometimes it feels like this tiny piece of DNA will take everything from me.
But this is also hyperbole—women the world over undergo menopause, mostly natural menopause, and live to be sharp as a tack, like my ninety-three-year-old grandma who still remembers the names of all the horses on the farm she grew up on in the 1920s and 1930s, does the crossword every day, and can tell you exactly how to miter the corner on a homemade quilt with a precision her arthritic hands can no longer match. Or my mother, who still teaches children to read and manages to juggle a schedule of activities that Superman would find challenging. She and my aunt—a similarly energetic woman—have both been through surgical menopause. I hope I will be like them.
I’ve had it with medical journals, though, with their statistics and numbers and likelihoods of this or that. I want to know what it’s like in the trenches; I want to hear what it’s like from other BRCA women.
I consider starting with the women in my family, but I can’t bring myself to ask my mother and aunt about their sex drives since menopause. So instead, I interview dozens of women with BRCA mutations and learn that everyone responds differently. Most women tell me it wasn’t as bad as they thought it’d be, especially with hormone replacement, though it quickly becomes clear that figuring out dosage and type can take time to get right. This heartens me. One woman tells me it’s the best thing that has ever happened to her. “I love being menopausal,” she says. No more periods and cramps, no more cyclical mood swings or birth control. “Oh yeah, I love it,” she reiterates. “I would highly recommend it to anyone.”
An hour later I’m talking to a different woman on the phone. She’d been athletic and toned before her oophorectomy at age forty-three. Now, five years later, she tells me sadly, “I was at peak, and I don’t think I ever will be again.” Even her muscle tone changed, she says. Due to a previous bout with cancer, she cannot take hormone replacement therapy. In the wake of the operation, she tells me,
My cholesterol has gone up, bone density has gone down. I have a lot more physical signs of aging, and my sexuality has changed a lot. My libido has plummeted. My orgasms are a lot weaker—not the same orgasmic experience at all. I feel like with the change of my sexuality a part of me is gone, a part of my identity is gone. When I look at pictures of myself from before, you know, the big before, it’s a little upsetting to me. I feel aggrieved and I feel grief for the part of me that died. I think there’s a bit of a code of silence there too, because not everyone has that experience.
Surgical menopause contains multitudes; it can be the best or worst thing in the world, and I won’t know how it is for me until I try it.
Of course, loss of ovaries also means loss of childbearing ability. No more ovaries, no more eggs—unless you’ve frozen some, of course. It’s a pretty final sort of birth control.
At the time of writing, I’m in my early thirties, and I think I probably do want kids. But along with the idea of fertility, the specter of ovarian removal also raises questions about whether it’s ethical for me to do so. For a long time, I went back and forth on this question. On one hand, having medicalized so many other parts of my life, I am reluctant to introduce technology into what feels like the last natural lady process my body has left: conception and childbirth. There are also ethical concerns about whether BRCA is really so terrible that it needs to be wiped from the world—it’s not certain that a BRCA carrier will develop cancer, and there are potential, if sucky, treatments for the condition to mitigate against these. On the other hand, the cycle could stop with me. I could ensure that the horror that has plagued my family for generations ends here, especially given that at least one study suggests that BRCA positive women are slightly more likely to have female children.
The idea of breeding a baby without BRCA entices me until I learn more about the available options. If I want to have non-BRCA biological children, as opposed to adopting, then there are two choices: preimplantation genetic diagnosis and prenatal diagnosis. The first involves in vitro fertilization (IVF). Basically, scientists combine egg and sperm from a woman and her partner outside the womb, test the embryos for BRCA when they are very small—six to eight cells big—and transfer a couple without mutations into the mother. It’s expensive and comes with all the risks of IVF, like multiple births, premature delivery and low birth weight, miscarriage, ovaries that become painfully large, and ectopic pregnancy, in which the embryo implants into the fallopian tube and must be terminated. There may or may not be a slight increased risk of birth defects and of elevating the ovarian cancer risk of the mother thanks to injectable hormones used during the egg-retrieval process, which is a complicated medical procedure in itself. The certainty of having a non-BRCA baby is offset by the risk of losing the baby, birth defects, having multiples, and a possible increase in ovarian cancer risk. No thank y
ou.
Prenatal genetic diagnosis involves getting pregnant and genetically testing the fetus, and then deciding whether to abort if it is BRCA positive. There’s a 50 percent chance that I’d get pregnant with a BRCA baby, so it’s possible I’d have to do this more than once. The idea of carrying a wanted pregnancy—maybe several times—to the end of the first trimester and then aborting it because it happens to carry my least-favorite gene, well, I don’t think I’m emotionally equipped to do that.
If I’m able, I’d like to have my own biological children. Of course, a study has linked BRCA1 mutations to early ovarian failure, so maybe I won’t be able to. But I’d like to try. It’s a human desire and one I don’t apologize for. In some ways, I feel that what the BRCA mutation hath given—a work ethic and a life planned to make my achievement goals early—is perhaps as much as it hath taken away.
The other thirty BRCA carriers I spoke to didn’t yield much consensus on the procreation question, though everyone agreed that it’s a heavy decision. Many of the men and women I spoke to had already had children by the time they tested for the gene, so their thoughts about whether they’d make that decision knowingly were purely theoretical. One man’s story in particular stood out to me. He had tested positive for a BRCA2 strain linked to pancreatic cancer, and when we spoke he was in remission from this lethal disease. He had a young daughter. “I worry, what kinds of decisions does she have to make?” he told me.
Like first of all whether to be tested or not. And do you tell your husband or your prospective husband that you have this gene that might give cancer to your kids? And do you have kids early or freeze embryos or decide not to have kids? I lament the fact that she will have to go through this.
It’s hard for people of any generation to grapple with. This same man had inherited his BRCA2 mutation from his father. Shortly after he was diagnosed with the pancreatic cancer that doctors believed would quickly kill him, he went to dinner at a restaurant with his seventy-six-year-old father, his two siblings, and all their kids. His sister and brother had asked his father whether, if he had known about his BRCA mutation all those years ago, he would have had children. “He broke down crying in the restaurant based off that question, which I didn’t know they were going to ask…. He’s a very stoic person and normally would not break down whatsoever.” While he wept, he explained to the family that it was a difficult question. On one hand, it would mean giving up the children sitting in front of him, but on the other hand, one of those kids had pancreatic cancer with what was at the time a terminal prognosis. As his son, who had been cancer-free for two years at the time we talked told me, “I tried to console him and say I essentially decided myself I was going to go ahead and have kids, and of course I would let my wife make the decision as well, but my glass half-full is that there will be something to fix this by the time they have to face this.”