Most women are told to start regular mammograms at age 40, with the goal of catching breast cancer early and saving lives. Yet despite advances in mammography technology and medical treatments, breast cancer remains the second leading cause of cancer death for women in the U.S. and the most common cancer in women except for skin cancer.
Breast cancer is also the most common cancer among adolescents and young adults (ages 15-39), accounting for 30% of cancers in this age group. This rate has been rising for nearly the past two decades.
With more women under 40 getting breast cancer – many of whom are diagnosed at a late stage – does the age-based approach to screening still make sense?
The WISDOM study seeks to answer this question by testing a personalized approach to screening for women as young as 30, compared to standard-of-care annual mammograms beginning at age 40.
Individualized Risk
WISDOM stands for “Women Informed to Screen Depending On Measures” of risk. The study, which enrolled 50,000 women across the U.S., was launched in 2016 by Laura J. Esserman, MD, MBA, director of the UCSF Carol Franc Buck Breast Care Center at UC San Francisco, a professor of surgery and radiology at UCSF, and a practicing surgeon and breast cancer oncology specialist.
The five-year trial compares two approved screening approaches: annual mammograms for all women, starting at the age of 40, or a personalized approach to breast screening that is based on a woman’s individual risk factors for breast cancer, such as her breast density, genes and family health history.
“The WISDOM trial is an exciting opportunity for all of us to participate in a program that will help us learn who’s really at risk for what kind of breast cancer,” says Dr. Esserman. Dr. Esserman is also the founder of the University of California-wide Athena Breast Health Network, whose member institutions are part of the study.
In the study, women ages 40-74 were placed in two groups; each filled out online questionnaires about their health history. Based on their group, participants received screening recommendations on when to start and how often to have mammograms.
The Annual Group of the study recommends annual mammograms starting at age 40, following the guidelines of the majority of professional societies in the U.S. At the end of April, the U.S. Preventive Services Task Force updated its guidelines to recommend that women at average risk for breast cancer start screening at age 40, lowering the age from its previous recommendation of age 50.
In Dr. Esserman’s view, all of the current guidelines – and how they are developed — are problematic.
“The same data is being analyzed and re-analyzed,” she notes. “There is no ability to personalize screening recommendations based on risk for specific tumor types nor to customize prevention recommendations.”
In the Personalized Group of the WISDOM study, women receive a personalized plan with recommendations on how often and when to get screened based on their unique risk factors for breast cancer. Participants also receive a kit to provide a saliva sample for genetic testing.
This personalized approach is a practice that the study is evaluating and is based upon international screening guidelines.
“WISDOM uses the full spectrum of existing and emerging risk factors, including a full understanding of the contribution of inherited genes,” Dr. Esserman explains. “Single gene mutations as well as the combination of smaller genetic factors can help us predict the risk for fast- and slow-growing cancers.”
In both study groups, mammogram reports are collected for women who have had a mammogram in the past. At the end of each study year, participants fill out a survey to make updates on any changes in their breast health and family history. They then receive new screening recommendations based on those changes.
Surprising Genetic Findings
In 2022, WISDOM’s genetic counselors reported initial results from the personalized group. They learned that out of the nearly 17,400 people tested for genetic mutations, only about 3% had them.
But within this small group, there was an unexpected discovery: a substantial proportion of mutation carriers (24%-46%) reported no family history of breast cancer in first-degree or second-degree relatives, with over 60% without a first-degree family history.
Currently, health care providers may only advise genetic testing for women with a first-degree family relative with a history of breast cancer. These findings could influence strategies and guidelines around genetic testing for the general population.
Fast-Growing Cancers
In October 2023, a new version of WISDOM was launched allowing women as young as age 30 to enroll in the study, with the goal of offering breast cancer risk assessment, including genetic testing, to thousands of younger women who could be at higher risk of developing aggressive cancer.
WISDOM 2.0 enrolls women ages 30-74, who are eligible to join the “Personalized” arm of the study. The goal is to identify the small percentage of women at very high risk for breast cancer, get them screened earlier and provide prevention strategies.
“If someone develops cancer in their 30s, they are usually aggressive and no matter how often you screen, those cancers will grow so quickly that your next mammogram may be too late for some good treatment options,” says Allison Fiscalini, MPH, director of the Athena Breast Health Network and WISDOM Study.
Along with expanding enrollment to include women as young as 30, WISDOM 2.0 uses an updated risk model that can help predict the risk of developing fast-growing cancers.
“There are lots of risk models out there with different components and they weigh risk factors slightly differently,” Fiscalini explains.
“We’re using the Breast Cancer Surveillance Consortium risk model, which brings in race, ethnicity, breast density, prior biopsies – which some of the other models don’t include. And when we combine these with a unique genetic test not routinely available to assess genetic risk, we are providing a more comprehensive risk model.”
She notes that some other models were largely developed based on women of European descent.
The WISDOM team has already implemented risk models specific to Latina and Asian women and is working on developing a model specific to Black women.
Black women are more likely to die from breast cancer than any other race or ethnic group at any age. This is partially because they have a higher risk of triple-negative breast cancer, which is especially aggressive.
Those who learn they are at higher risk in the study will be offered genetic counseling services and risk reduction strategies, as well as a Breast Health Decision Tool, which has suggestions for prevention and tools to understand risk. Women are encouraged to bring this information to their doctors.
Environmental Harms
Since the majority of women who get breast cancer don’t have a family history or genetic marker, the researchers are trying to determine if there is a risk factor that hasn’t been investigated or adequately studied.
One of these is environmental exposures. “Some of those exposures might alter how your genes are expressed and increase the risk for developing breast cancer,” Fiscalini explains.
While it has been known that certain pollutants are linked to breast cancer risk, robust data from environmental monitoring was not available when the study first launched. With advancements in the data and science, the study team seeks to learn more about how exposures influence breast cancer risk.
The researchers are gathering information about women’s occupational and residential history. Several different types of environmental exposures will be examined, including air and water pollution, superfund site proximity and chemical exposures associated with several occupations.
They will then investigate whether the information collected is predictive of breast cancer risk and whether adding this information to risk models improves the accuracy. If it is determined that adding this information does improve accuracy, the study team will integrate this new model into a subsequent version of WISDOM.
Risk Assessment as First Step
With limitations of the current age-driven screening guidelines, the WISDOM team is recommending that every woman have a comprehensive risk assessment when they are younger – at age 30.
“That will help us to find the people we know with explained risk factors and offer them prevention and screening at a younger age, especially genetic mutation carriers who have no family history,” Fiscalini says.
Unless a woman has a family history, they’re usually not being assessed, according to Fiscalini, who adds that not all providers are trained in breast cancer risk assessment.
“Our goal is to provide more education,” she says. “If we find those people who should be concerned about breast cancer, we can have a really big impact. This is especially important for women at the highest risk.”
Fiscalini notes that many women are at low risk and may not need screening until their 50s.
Joining the Study
WISDOM 2.0 seeks to enroll another 50,000 women, with at least 10,000 Black women.
People ages 30-39 across the country are encouraged to join. Women are eligible if they have not had breast cancer or ductal carcinoma in situ.
“This study is an opportunity to get free access to the best available data and tools, and to generate the information to create better and more informed guidelines in the future,” Dr. Esserman says.
For more information, visit the WISDOM website.
