Bringing WISDOM to Breast Cancer Care

Dr. Laura Esserman answers the door of her bright yellow Victorian home in San Francisco’s Ashbury neighborhood with a phone at her ear. She’s wrapping up one of several meetings that day with her research team at University of California, San Francisco, where she heads the Carol Franc Buck Breast Care Center. She motions me in and reseats herself at a makeshift home office desk in her living room, sandwiched between a grand piano and set of enormous windows overlooking her front yard’s flower garden. It’s her remote base of operations when she’s not seeing patients or operating at the hospital.

The research Esserman is discussing is a potentially groundbreaking study that could transform the way women are screened and treated for breast cancer. She and her team hope to bring a more personalized approach to figuring out each woman’s risk for the disease, and tailor a screening and treatment program appropriate for that risk.

Not all doctors in the field are convinced that such a radical change is even needed, noting that current mammogram screening is sufficient in detecting most cancers. And some doctors aren’t quite willing to give up the tried and true, if crude, way of advising women when to get mammograms based on their age. Esserman knows she’s got a lot of convincing to do.

That’s why she launched WISDOM, Women Informed to Screen Depending On Measures of risk, in 2016. After years of watching women diagnosed with the disease get the same, drastic treatment of disfiguring surgery or brutal chemotherapy and radiation, Esserman believed doctors not only could but should be able to do better. She also knew that to convince them, she needed data.

Right now, women are screened for breast cancer essentially based on that one major risk factor: age. And experts can’t even agree on that. After advising women to start getting yearly mammograms at age 40, the U.S. Preventive Services Task Force in 2016 advised women between ages 40 and 50 to make individual decisions about screening after discussions with their doctors, and recommended that women start screening, with mammograms every two years rather than every year, by age 50. The American Cancer Society, meanwhile, suggests women start annual screening at age 45. Major cancer centers still advise women to start screening yearly at age 40. “When you have so much controversy and so many smart people believing in very, very different things, you need to break the deadlock,” Esserman says. “And the only way to break the deadlock is with wisdom. The only way you get wisdom is to run a trial and test a new approach and give yourself a chance to make things better. I don’t want to end my career doing the same thing I did when I started. I want things to be different, and I want them to be better.”

While age is certainly an important risk factor for many cancers, including breast cancer, other contributors, including a woman’s genetic makeup as well as what she eats and how much alcohol she drinks, aren’t incorporated into screening guidelines in a formal way, mostly because there isn’t convincing data to support using them.

That’s where Esserman hopes WISDOM will make a difference. Rather than starting with a broad guideline like age, Esserman flips the script. She starts by asking patients, “What do we do with you?” It’s not a question born of frustration or exasperation or even genuine bewilderment. For her, it’s a thought exercise, a conscious effort to think about the person sitting in front of her as an individual and not a statistic, as someone with her own complicated amalgam of risk factors and behaviors that tilt her particular chance of developing breast cancer one way or the other. It’s also a reminder that each woman has her own, personally calibrated way of measuring risk and setting a threshold for how much risk she is comfortable with. The question forces Esserman to remember that what breast cancer experts generally advise when it comes to screening and treatment is just a starting point, and not the final answer. What may be right for hundreds of thousands of women isn’t necessarily right for the woman sitting in her office who wants to know how worried she should be about breast cancer.

That might seem obvious enough, but it’s actually not. Breast cancer diagnosis and treatment are stunningly effective, and far more advanced than they were even a generation ago. That’s led to a stunning 40% decline in mortality from the disease from 1989 to 2017. But Esserman thinks we can and should be doing better. The current recommendations for breast cancer mammogram screening mean some women with very low risk of the disease are screened more often than they need to be, while others who are at higher risk aren’t screened frequently enough to catch faster-growing cancers.

“We have got to do better than we are,” she says, fixing her laser-like gaze on me with an intensity that mirrors her passion for the subject. “We have 265,000 women a year being screened and getting diagnosed with breast cancer, over 40,000 women a year dying, despite everything we’re doing. Does anyone think that is good enough? My goodness, no—by no means.”

More sophisticated imaging, as well as lab-based tests of breast cancer biopsies, make it clear that breast cancer is not a single disease but many different ones, and that even an individual patient may harbor different types of tumors. Yet, argues Esserman, studies on breast cancer and the resulting recommendations about how to screen and test for it “treated everybody as if they had one disease, or that one size fits all. It’s like the different perspectives you get when you snorkel or scuba dive—viewed from the water’s surface, everything looks uniform, yet slip underwater and you’ll find a teeming universe of different life forms.”

WISDOM is an ambitious effort to find answers to the unanswered questions about breast cancer. Which women are at highest risk of the disease? Which risk factors, from genetics to family history to lifestyle factors, are most important in influencing that risk? Which women don’t need to get mammograms every year? How can doctors better answer questions about breast cancer risk among women of different racial and ethnic backgrounds? Are their cancers different? “The only way to do better is to know better,” Esserman says of these still-yawning gaps in breast cancer knowledge. “Every woman, regardless of her race, or ethnicity, is at risk for any one of these types of [breast] cancers. We just don’t know which one yet. We are not sophisticated enough to know who is at risk for these cases, but I believe that can all change. That’s why we do the WISDOM study.”

Since launching in 2016, WISDOM has enrolled 35,000 women ages 40 to 74 years old from across the U.S., with the ultimate goal of including data from 100,000 diverse women from different racial, ethnic and socioeconomic backgrounds. Each woman is asked to fill out a 50-question survey every year for five years about her family history and lifestyle habits such as diet and exercise patterns, as well as her health status including weight, blood pressure and other medical metrics. She also chooses whether she would like to be randomly assigned to a traditional breast cancer screening schedule in which she follows current advice and gets a mammogram every year, or whether she would like to get a more personalized screening “prescription” based on her particular risk profile. If she chooses the customized approach, the WISDOM team sends her a DNA testing kit; she provides some saliva that is then analyzed for around 10 major breast cancer-related genes. Based on the results of that genomic test, as well as her survey answers, the WISDOM team gives her a proposed screening schedule—it could be a yearly mammogram, mammograms every two years if she is at low risk or, if she is at higher risk, alternating mammograms and MRIs every six months. All of the advice falls within the guidelines of screening recommendations by the various cancer bodies; none of the screening schedules ask women to screen any less than what is currently recommended.

“The tailoring of screening actually identifies a group at lower risk, where, what a blessing if you don’t have to do something like an annual mammogram, then don’t do it,” says Esserman. “And it also allows us to do more for the people that are more likely to benefit from additional screening or more intensive surveillance. In my experience, the better we are at understanding biology, the more effective we will be. And the better outcomes we will have not only because people will survive longer, but because there will also be less toxicity from treatments that they might not necessarily need.”

It’s the Holy Grail of where she hopes WISDOM will take us: to a smarter and more efficient way to manage women when it comes to breast cancer. “The WISDOM trial is an important step in the right direction, which is trying to clarify the optimal screening intervals for women,” says Dr. Larry Norton, medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center. “The most important thing about WISDOM is that we’re doing it. Whatever the results of the study are, they are going to be informative in terms of the next study and next study and so on in the process.”

In the past, the way that doctors think about screening, and the inertia of existing protocols, meant that the idea of even testing a different screening approach wasn’t a given. After hard-won efforts to raise awareness about breast cancer and the importance of screening regularly—preferably once a year—as the best way to prevent disease and death, many breast cancer experts remain reluctant to shift women away from annual screening. Some predicted that any move away from at least yearly mammograms would lead to a spike in cancer rates and more women being diagnosed with advanced cancers that weren’t treatable.

Dr. Daniel Kopans, emeritus professor of radiology at Harvard Medical School and Massachusetts General Hospital, has been one of WISDOM’s most vocal critics. “WISDOM is based on a failure to understand the facts,” he says. “The randomized, controlled trials proved that early detection saves lives for women ages 40 to 74 years.” Kopans takes issue with the fact that in making the case for WISDOM, Esserman relies on a Canadian study that showed yearly screening wasn’t lowering deaths from breast cancer, and therefore researchers needed to revisit the advice to screen annually. That study, he says, was skewed to include more women with harder to treat or advanced cancers, so the benefits of annual screening weren’t obvious.

In addition, Kopanssays, because WISDOM allows women to choose whether they get the recommended yearly screening or the personalized regimen, it’s not an unbiased comparison of the two; there could be selection bias that skews the findings. He acknowledges that WISDOM’s intention—to compare annual screening to biennial screening—will be useful, but doesn’t believe the trial is designed to provide reliably scientific answers. The genetic, lifestyle and other risk factors also may not be the right ones to analyze. “The vast majority of women diagnosed with breast cancer each year have none of the known elevators of risk,” he says.

Esserman counters that while existing guidelines may be adequate, they aren’t enough. The current screening recommendations are based on studies done at a time when doctors knew much less about the different types of breast cancer, and don’t take into account newer ways to analyze cancers through imaging and genetic testing. And even with screening, she says, 40,000 women a year still die of the disease.

She says only the data from women who are randomly assigned to a screening regimen will be included in the final scientific analysis, so there won’t be selection bias in the data. And she says there is no evidence that more women will die of breast cancer if not all of them are screened every year. “I don’t think there’s any evidence for that at all,” she says, pointing to other countries where women are screened every other year, or even the U.K., where women 50 to 70 years get mammograms every three years. “The best way to answer that question—and there are deep divisions on this; it’s almost religious, of people who feel strongly one way or the other—the best thing to do is to test it in a trial. I’m not saying let’s go out and do personalized screening. I’m saying, ‘let’s test it, let’s let it have its day in court.’”

Esserman’s position comes from years of painstaking work studying breast cancer cells, and trying to understand the different ways they can present in patients. She was among the early researchers who recognized that since not all breast cancers are the same, they should not all be treated in the same way, and that contrary to initial understanding, not every cancer detected in breast tissue must be so aggressive and fast-growing that it requires rapid, radical and toxic treatments. Rather, there are indolent cancers, similar to those in the prostate, that grow more slowly, or hardly at all. These likely aren’t as dangerous to people’s health. “People had trouble believing that,” she says. “And that’s why I worked so hard to molecularly characterize them and show that they existed.”

That work, especially with cancers known as ductal carcinoma in situ (DCIS), or very early lesions that some doctors believe are not even cancerous yet, convinced her that treating all women as if they harbor fast-growing tumors that would spread throughout their bodies wasn’t doing them—or the health system, in terms of financial cost—much good. If DCIS doesn’t pose an immediate threat to a woman’s health, is it necessary to have her risk potential complications from surgery, chemotherapy or radiation to remove it? At Duke University, another pioneering breast cancer expert, Dr. Shelley Hwang, is putting this idea to the test. She’s leading a study comparing women diagnosed with DCIS who are assigned to careful monitoring of their growths with a mammogram every six months, or treatment with surgery or radiation according to current guidelines, to see how the rates of cancer recurrence or spread compare in the two groups. “I think we are all benefiting from taking a big step back, and looking at the big picture of what we have been doing that hasn’t been benefiting the patient in any way,” Hwang says. “The next challenge is going to be to pull the rest of society with us in saying that we now have biomarkers, we have data and clinical trials that show us that doing a lot of the things we were doing in the past that we thought we had to do, we’ve now shown that we don’t really need to do. The place to do that is in people with very low-risk conditions—that’s where the opportunity is to really start digging into ideas of de-escalation.”

Finding those sweet spots where doctors can pull back on screening and treatment recommendations is Esserman’s goal. “In the late 70s and early 80s when I was in medical school and training, women were taken to the operating room and they had no idea if they actually had breast cancer or not,” she says. “They would do a frozen section [biopsy] in the operating room; we would have no idea what was going to happen; it was a terrible experience. And I watched this as a medical student.” While she was working with mentors who began questioning whether all women needed chemotherapy, and starting to build profiles—based on more sophisticated understanding of what was driving different cancers in different women—Esserman was inspired to focus on breast cancer. “I thought, ‘here is an opportunity where biology could lead to different outcomes if we applied it properly,’” she says.

That questioning of the status quo has become a feature of Esserman’s career. After finishing medical school at Stanford, she was offered a fellowship to pursue a business degree. It was during that program that she first hatched the idea for a more comprehensive approach to managing breast cancer, from screening to treatment to research trials, and finding innovative ways to improve care. For a business school project, she recruited fellow student Robin Joy, now senior vice president at DocuSign, to study ways that different countries screened for breast cancer, and developed models for figuring out which screening schedule—yearly, every other year, every three years—led to the best outcomes for women. “That became the foundation for much of what I’ve done around screening for the rest of my life,” she says.

It also established a trait Esserman carried with her to UCSF to direct the breast cancer center there: questioning the status quo to ask, “can’t we do better?” As basic research on breast cancer revealed the universe of different diseases under the seemingly uniform surface of the singular term of breast cancer, she became more convinced that the only way to dramatically keep new breast cancers from occurring, and from saving more lives among those that did, was to develop better ways of measuring an individual woman’s risk. Esserman took her cue from heart disease—in the 1940s, the Framingham Heart Study revolutionized the way doctors treated the leading killer of Americans. That groundbreaking trial, which initially involved more than 5,000 people and has now blossomed into tens of thousands, including the next generations of the original participants, created a new precedent for differentiating people’s risk of heart disease by collecting information on a suite of things influencing that risk—from blood pressure to cholesterol to exercise, diet and family history. The study produced an algorithm for weighting those factors, known as the Framingham Risk Score, that gave people a rough predictor of how likely they were to have a heart problem in the next five or 10 years. Esserman is convinced the same should and can be done for breast cancer risk.

“The Framingham study started by understanding people’s risk,” she says. “And then they built risk models and started thinking about which risk factors contributed to heart disease—blood pressure, weight cholesterol—and one after the other they started going after each one of these. And they brought the risk of dying from heart disease or getting a stroke way down. We can do that in breast cancer.”

Having such a formula for assessing risk would have a profound impact on women on a number of different levels. For Shelia Bauer, joining WISDOM has already changed the way she manages her breast cancer risk. Bauer, 74, who lives in Cape Cod, Mass., joined WISDOM after her daughter, who works with Esserman on recruitment efforts, recommended it to her mother. Bauer’s sisters, who were twins, both died of breast cancer, and for most of her life, she thought that she too carried the same genetic lottery that had given her sisters the disease. For 30 years, she got both an annual mammogram and an annual MRI of her breasts since she has dense breast tissue, and studies show that MRIs are more likely to pick up potential tumors. But the latter were particularly anxiety-provoking for Bauer, since she is claustrophobic. “Having to go to a breast MRI face down in an MRI machine in itself has been extremely stressful to me, but I’ve done it because that’s what the protocol has been.”

As part of WISDOM, Bauer received a genetic testing kit in the mail, and sent in a saliva sample so her DNA could be analyzed. To her surprise, she was negative for nearly 10 major breast cancer genes. The WISDOM team recommended that she could scale back to getting just a mammogram once every other year, which eases her concern over the accumulated radiation exposure she’s had over the past 30 years of getting the annual scans. It also means she doesn’t have to enter the tight space of the MRI tube as often either—only if the mammogram picks up something unusual. “That was an enormous relief for me,” she says.

On the flip side, WISDOM, and the more customized lens through which it looks at women’s risk, could also uncover hidden risks that mammograms might not find in time. Heather Mann, 49, from San Francisco, never thought she was at risk of developing the disease. Her genetic test from WISDOM, however, was positive for a mutation called CHEK2, which is known to increase breast cancer risk. Her regular mammogram, just after she received these genetic test results, showed nothing unusual, but an MRI, which she got because the genetic test results indicated she was at higher risk for the disease, revealed a suspicious growth. A biopsy proved it was cancer— t was small, and detected early, but still malignant. “We really thought they needed to go back to the lab and recheck the results because they had the wrong patient or the wrong phone number,” she says. “I was absolutely in shock.”

But she was grateful that she had joined WISDOM, which led to her getting the genetic test and MRI that exposed the cancer. “To me, this is one of the great success stories of WISDOM,” says Esserman, who removed Mann’s tumor with surgery and is currently treating her with targeted anti-cancer drugs. “Her tumor was very small, and she was able to do a fairly small surgery and take it out. And CHEK2 mutations are almost all hormone-positive, so by taking endocrine therapy, she reduced the risk that she would get breast cancer on the other side, and she didn’t feel that she had to have a bilateral mastectomy.”

In fact, during Mann’s appointment with Esserman about her surgical options, she asked her father, a retired physician who treated cancer patients with radiation, to join by speaker phone. “He was very worried for me, and he was like, ‘do a double mastectomy right away, just get rid of it,’” she says of the cancer. “Laura jumped in and talked about breast conservation, and I thought, ‘that’s so awesome.’ To feel like you can just cut off your breasts and it’s no big deal is completely inaccurate. I loved her approach of ‘let’s do what we can to keep your breasts and not put your life in danger; we have many ways. I thought that was really great.”

So far, however, there are just under 10 major genetic markers tied to breast cancer that tests seek out. There are certainly teems of other combinations of genetic mutations that, while alone might not contribute to a significant increase in risk, together might. Having the genetic tests of the tens of thousands of women will help the WISDOM team start parsing out those so-called polygenic, high-risk combinations. “Polygenic risk scores have been percolating for a couple of decades now,” says Dr. Jennifer Litton, vice president of clinical research at the University of Texas MD Anderson Cancer Center. “They have been interesting, but certainly nothing has gotten to the point where I thought they should be routinely applied to everyone yet. When we think of genetic risk, everything dwarfs when compared to the BRCA mutations, but that doesn’t mean there isn’t quite a bit more we can learn from other constellations of genes. I think it’s time to start addressing that question.” That’s why Litton says she would encourage any of her patients to join the study if they were interested.

Bauer, for one, appreciates the evolution in thinking that WISDOM represents. “Things haven’t changed in the past 30-odd years in the way we do testing,” she says. “I’ve been waiting a very long time for somebody like Dr. Esserman to come up with maybe a new approach and new protocols and have a more personalized approach to individuals. I believe that the way we look at breast cancer is ‘one size fits all’ right now. It needs to change. We are all individuals; we don’t all have the same family backgrounds, we don’t all have the same ethnic backgrounds, so why are we all being tested the same way?”

For women of color in particular, such data could be life-changing, since most guidelines and data on breast cancer have come from studies of white women of European descent. “I don’t experience the screening recommendations in the same way that white women do,” says Yvette Gullatt, chief diversity officer for the University of California, who joined the study to improve the information on breast cancer that’s available to other Black women. “I experience breast cancer in Black women as highly aggressive and lethal. I had a former student of mine [a Black woman] pass away earlier this year; she left a 3-year old daughter. Her breast cancer was discovered while she was pregnant, and essentially early, but two and a half years later, she’s gone,” she says. “I’ve had white colleagues who were diagnosed with breast cancer and go to radiation in the morning, and are back at work by 10 a.m.; they never miss a day. We need more studies like this because [researchers] need more data in order to diagnose and treat us better.”

Esserman and her team are working closely with community advocates to increase awareness and education about clinical trials among Black women, who already have a deep mistrust of the medical system given notorious episodes of medical exploitation, including the Tuskeegee and Henrietta Lacks experiences in which Black patients were used in research studies without being fully informed of their participation or the potential risks of participating. It’s especially important, since about 25% of breast cancers among Black women are triple negative, a highly aggressive form missing the locks to three hormone-based drug “keys” that have become effective weapons in fighting the disease in recent years. Without these locks, the drugs can’t work, and tumors grow more quickly and seed new growths in other parts of the body. Most of these cancers also start in younger Black women, under age 40, so they aren’t picked up because they aren’t getting mammograms yet according to current guidelines. “There is this background genetic information that we can use to tailor risk assessment in different ethnic groups,” says Esserman. “Most of the studies where these risk factors have been developed are mostly from women of European ancestries. So we really, really, really want to encourage African-American women, Latina women, women of all backgrounds to participate in this study. This is the way in which we can make sure that the results of WISDOM are helpful for the whole population.”

As part of WISDOM’s recruitment, Esserman has also reached out to the VA health system in the U.S., to include female veterans whose risk of breast cancer may be related to not just hereditary factors but environmental exposures during their service. Lisa Edwards, a veteran who was discharged from the Army in 1989, says the study is also an opportunity to raise awareness and resources for women’s health in the VA system in general. Edwards, who was getting sporadic mammograms, had two needle biopsies when doctors found suspicious growths during her screenings. After joining WISDOM, the genetic test revealed she did not have a genetically higher risk of disease, but because of her dense breast tissue and history of biopsies, the team recommended she continue with yearly mammograms. But because her VA in Wilkes-Barre, Penn., does not have a mammogram machine, Edwards goes to an imaging center nearby for her yearly screening. “As female veterans, we faced chemicals and exposure just as the men did. But because our bodies react differently, I think in the future it may help researchers understand certain cancers from chemicals that react differently in women than in men,” she says.

On the same day I visit Esserman at her home, she is boiling over the Texas governor’s decision to ban abortions past six weeks in the state. As an organizer for the annual San Antonio Breast Cancer Conference, a major gathering of key leaders and physicians from around the world involved in the research and clinical care of breast cancer, she was busy writing an op-ed calling for doctors and scientists to boycott the meeting in protest. “Where is the sense of outrage?” she asks. In the commentary, which she sent to both the New York Times and the Washington Post, she and seven other organizers argued that a conference focused on finding ways to improve treatment for disease that mainly affects women should be held in a state that discriminates against women.

Esserman isn’t afraid to speak her mind, especially when it comes to advocating for women’s health. She jokes that her husband, Michael Endicott, a professional photographer, warned her throughout last year that her unfiltered comments about the Trump Administration’s views on science and handling of the COVID-19 pandemic would jeopardize her government-based grant funding. But Esserman wasn’t concerned—a singer and piano player, she’s penned a political parody musical entitled Audacity that makes her views on Trump very clear.

Esserman’s sense of social justice was nurtured from a young age by her parents Ron, who was in the auto business, and Charlene, a teacher and community advocate, both of whom were active civic leaders in Miami, where the family moved when Esserman was 10 years ol. The young Esserman was fascinated by the story of Marie Curie after reading her biography. “I still remember the book—the tattered leather cover,” she says. “I was so impressed by her observations and how she turned those into major discoveries by her persistence and her ability to succeed as a woman. When I was little, women did not have the opportunities they have today. And I felt like I, too, could maybe grow up and make a difference in science.”

Esserman nurtured her love of science along with a talent for music. She admits she once took a stipend when she was a research assistant in medical school and spent it on a piano—”I was very thin and hungry for a quarter or two, but I had a piano that I have had ever since.” She’s just as likely to break out into song as she is to cite statistics about the slow progress in breast cancer care, and early in her career as a surgeon, started a unique singing tradition for her patients. During her second year at UCSF, she noticed one of her patients in the operating room was getting extremely anxious about the upcoming procedure; it was a Saturday, and the patient needed surgery because of a complication. “I was just watching her blood pressure go up, and my blood pressure was going up watching that,” she says. Esserman had just seen Phantom of the Opera the night before, and she asked if the patient liked music. She did, and Esserman began serenading the operating room with “All I Ask Of You,” beginning with the appropriately reassuring lyrics “No more talk of darkness/ Forget these wide-eyed fears/ I’m here/ Nothing can harm you/ My words will warm and calm you.” Her patient’s blood pressure dropped back down. “I thought, I will make this a part of what I do,” she says.

It’s a tradition she continues today with every patient on whom she operates. But rather than deciding herself what she’ll sing, she asks her patients for their favorite song and learns the lyrics so they can hear them as they slip under anesthesia. The requests have ranged from Broadway tunes to arias (Esserman requests a week to prepare for those; for the rest, she picks up the melodies and lyrics pretty quickly). For Mann, Esserman sang the aptly worded “For Good” from Wicked. “A lot of times in [medical] training people say, ‘be guarded, and don’t share.’ That’s just not my style. I think it’s important to share a little bit of yourself and for people to share a little bit of themselves. Caring for someone is an art, it’s a privilege.”

She’s still defending her conviction that doctors can and should improve on the way they evaluate women’s risk of breast cancer. If women are better segregated into lower and higher risk groups, then doctors can better advise them about how to potentially prevent the disease as well. “We are working with data that is old,” says Litton from MD Anderson. “It doesn’t take into account in many cases the imaging techniques we are using now. It doesn’t take into account if you’re not a white woman. And it doesn’t take into account what we’ve known for a long time, that hereditary breast cancer has a different growth pattern. WISDOM is a start to trying to answer those questions.”

Norton also sees WISDOM as a catalyst for rethinking the way doctors calculate cancer risk—by looking for more precise markers of tumors in the blood, for example, that can indicate not just a breast cancer but any type of abnormally growing cell in any tissue in the body. And the idea of honing the crude models we now have of which genes contribute to cancer to the precise suites of mutations that confer the highest risk is also an important harbinger for how doctors might manage breast cancer in the coming years.

Esserman recognizes that WISDOM won’t fill all the gaps in our knowledge about breast cancer. “The WISDOM study is a start. This is the beginning of a change in screening; we’re going to build on this platform,” she says. “In my fondest dreams I hope, five years from now, that we might be able to really identify a group of people that are so low risk, they don’t actually need to get screened. I think that would be very exciting. As well, I think it would be fantastic if we really had a way to identify those women who are at risk for aggressive cancers.” Finding those women, she says, will allow doctors to start building trials to test ways to prevent these aggressive cancers from appearing in the first place or, at the very least, from progressing if they do. “The best outcome would be 10 years from now that the rates of breast cancer are half, and that the people who need screening are doing more of it, and the people who don’t need screening are doing less of it or not at all.”

Clarification added: The USPSTF advises that women under age 50 make individual decisions about whether to start mammogram screening.

Marc and Lynne Benioff, the co-chairs and owners of TIME, have been philanthropic supporters of Dr. Esserman’s breast cancer research. The WISDOM study receives software support from Salesforce, where Marc Benioff is chairman and CEO.