In an interview, Long says her own decision for bilateral mastectomy was fairly straightforward; her gene mutation was discovered shortly after a diagnosis of triple-negative breast cancer. But as a young woman who hoped to one day become a mother, she wanted to keep her reproductive organs as long as possible. How many years would be too long?
Long wanted data. She says she is most comfortable applying math to real-world problems, a habit reinforced by marriage to a behavioral economist with similar tendencies. As she describes it, even their take-out dining decisions are data-driven.
So she asked the doctors: Statistically, what would be the best age for me to undergo oophorectomy to avoid ovarian cancer? How would my cancer odds change if I delayed the surgery for five years?
Long found that no one — neither professionals at national cancer organizations nor the top BRCA experts at a dozen medical centers she consulted — could give her definitive answers. No established guidelines exist to advise BRCA mutation carriers of optimal ages for each surgery. The advice she heard most often, which included prophylactic salpingo-oophorectomy after completing childbearing, made no distinction between BRCA1 and BRCA2 mutation carriers, despite their starkly different risk factors, and did not consider the effect of these surgeries on quality of life.
"What scared me the most, when I asked about when I should have surgeries, was that I got a lot of different answers," Long recalls. "I am trained in statistics and making medical decisions under uncertainty, and I felt overwhelmed."
Long enlisted the help of Eike Nohdurft and Stefan Spinler from the Kühne Institute of Logistics Management at WHU in Germany, two colleagues she had worked with on a previous study that predicted Ebola cases in different locations in West Africa, using data from the 2014-2015 epidemic. Together, the three researchers turned her medical dilemma into a cold hard research question: At what ages should BRCA gene mutation carriers undergo prophylactic surgeries for optimal survival and quality of life?
Two years later, they have produced some answers.
Personalized Cancer Risks
The model that Long, Nohdurft and Spinler developed applies not just to Long's situation, but to any woman who carries the BRCA1 or BRCA2 gene mutations. Customized for each carrier's health status, the model potentially answers the questions: How do my odds of cancer change if I have bilateral salpingo-oophorectomy at age 28 versus 38, or any other age? How much are the odds reduced if I only have bilateral mastectomy? What if I never have surgery? And also: Given the downsides to each surgery, what are the optimal ages to undergo each, if at all?
The study, "Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies among BRCA Mutation Carriers," appeared in the September 2017 edition of Decision Analysis, an academic journal dedicated to research that establishes rational steps for making complicated decisions. (Jolie, a BRCA1 mutation carrier, famously made public her own decision to have both surgeries prophylactically in her late 30s.)
The model can't tell a woman whether she will or will not get a future diagnosis of cancer, Long explains. But it does allow her to see how her personal odds change if she chooses, or declines, certain prophylactic surgeries now. It shows how a woman's cancer risks change with her health and her age, in a way that Long found lacking in her own search for advice.
For example, a 30-year-old carrier who undergoes prophylactic oophorectomy will lower her risk of ovarian and breast cancer, but not as much as a woman who also undergoes prophylactic bilateral mastectomy. The model incorporates the odds for more than four million different health states, changing the statistical prognoses again for each prophylactic surgery.
In its current state, a statistician or other mathematically inclined professional is required to manipulate the model. But the researchers are working on a tool, possibly an app, that will allow individual carriers to enter their personal data and determine optimal ages for surgeries for themselves. They hope to have the program operational before the end of 2018.
"I've thought a lot about how I wish I could take this experience and scale it up to help more people," Long says. "Our ultimate goal of building an online tool is to make it as easy as possible for a woman to compare different strategies, personalized to her based on the latest available data, so that she can make an informed decision."
Accounting for Trade-Offs: Fertility or Peace of Mind?
If the sole goal of every woman with the BRCA mutation were to reduce her cancer risk as much as possible, Long explains, the recommendation would be unequivocal: all carriers would have both surgeries at age 18. But of course Long doesn't advocate that, because the decision is never that simple. Some women would rather live with the cancer risks than endure possibly unnecessary surgery. Some will move up plans to get pregnant and then schedule prophylactic surgeries after giving birth and breastfeeding. For others, peace of mind is worth the fertility and quality of life concessions that mastectomy and oophorectomy require.
Long wanted to incorporate the likely quality of life impacts from each procedure into the surgical strategy recommendations — guidance for whether or when to undergo bilateral mastectomy, bilateral salpingo-oophorectomy, both surgeries or neither —that the model would ultimately produce.
So the researchers looked at survey data that asked BRCA mutation carriers to rate these surgeries' detrimental effects, including cosmetic issues, the end of fertility and side effects of early menopause. The study accounts for these variances in quality of life over time, assuming, for example, that a mastectomy creates a temporary reduction and an oophorectomy reduces quality of life until a woman would otherwise be in natural menopause around age 50. The model's objective is to maximize future quality-adjusted life years, or QALYs, which captures both the length of life and average quality of each year.