‘We need to do better’: WISDOM study aims to ‘reimagine’ breast cancer screenings for women

Key takeaways:

• The WISDOM study compares annual mammograms for women vs. a personalized screening approach.
• Researchers encourage all women aged 30 to 74 years without breast cancer history to enroll.

A research study, WISDOM, is currently underway to improve breast cancer diagnosis timing and outcomes by comparing annual mammography with a personalized screening approach to identify women at highest risk for fast-growing cancers.

“Screening seems like it is very simple, but in fact, it is a complex story,” Laura J. Esserman, MD, MBA, the Alfred A. de Lorimier Endowed Chair in General Surgery, director of the University of California, San Francisco (UCSF) Breast Care Center and co-leader of the Breast Oncology Program at the UCSF Helen Diller Family Comprehensive Cancer Center, told Healio. “There is a lot that is not well understood and there are many opportunities to improve the way we screen. More knowledge and generating more modern data would go a long way to improving our approach to screening.”

About $10 billion to $20 billion is spent yearly on breast cancer screening with about 65% of women in the U.S. screened, Esserman said. And, while screening reduces the relative chance of dying of cancer, the kind of cancers detected via screening are usually slower growing, hormone-driven cancers with preferable outcomes, Esserman noted.

“The absolute difference that screening makes in reducing mortality is somewhere in the 2% to 4% range,” Esserman said. “So, it’s not huge, but screening could be so much better in general.”

Who should be screened?

Currently, every woman in the U.S. is screened as if they are at risk and have the same risk factors for the same type of breast cancer, according to Esserman. In addition, about 85% of fast-growing stage II and III cancers are not detected via screening, Esserman said, either because the cancers occur when people are younger than the recommended screening age or they occur fast between screens.

“We have to stop saying that the solution to breast cancer is everyone goes out and gets a mammogram. We have been doing that for decades,” Esserman said. “We still have 42,000 women a year dying of breast cancer, and we are detecting 300,000 breast cancers a year, and it is going up.”

Allison Stover Fiscalini

The aim of the WISDOM study is to improve breast cancer screening through personalizing mammogram schedules for every woman, similarly to personalization of treatments, since risk factors are not the same for everyone. This study compared annual mammography, which begins at age 40 years, with a personalized approach to screening based on individual risk factors such as breast density, genes and family history.

“One of the best things that we can do is start with risk assessment,” Esserman said “While it may not be perfect, it is better than not conducting a risk assessment at all. We can identify people at much higher risk and people at much lower risk. That allows people to make better decisions about how they want to screen.”

According to Esserman, about 2% of the population has an inherited breast cancer risk from mutations in one of the 11 major genes. WISDOM investigators aim to identify those at high risk for breast cancer early so they can be treated and prevent further adverse events.

“We want to help people understand not only how to adjust their screening, but how to think about prevention,” Esserman said. “As part of the WISDOM study, we have a tool called ‘breast health decisions.’ Anyone who joins as part of that personalized arm receives a personalized tool, so they can learn about their risk factors and steps they can take to individually improve their own breast health.”

Esserman said WISDOM results will likely be available by mid-2025; however, more efforts are needed to improve breast cancer risk assessment. Researchers observed no family history of breast cancer among 65% of women with mutations, which suggests family history alone is not the proper way to screen for inherited breast cancer risk.

How to enroll

The WISDOM studies are open to any woman living in the U.S. aged 30 to 74 years without a history of breast cancer, and enrollment can be completed from home, Esserman said.

“I want everyone to feel like they want their voice heard,” Esserman said. “It is a study about women for women to generate data to make the future better for themselves, their mothers, their daughters, their sisters, their loved ones and their community.”

Allison Stover Fiscalini, MPH, director of the Athena Breast Program in the department of surgery at UCSF, a WISDOM co-investigator, encouraged physicians to discuss the benefits of the WISDOM study with patients and consider participating in the study’s monthly breast health community forums.

“Physicians have a trusted relationship with their patients, and they could be that trusted voice to encourage patients to join a study,” Fiscalini said. “This is a very easy study to join. It can be done from home. There are no study visits. Participants can enroll via their phone, tablet or computer. The genetic test is mailed to their house.”

According to Fiscalini, all participant data is available via a secure, individual study portal and is not shared outside of the study team.

Future directions

Esserman said it is important to compare fast vs. slow-growing breast cancer tumors to improve prevention methods and available tools that may reduce risk for fast-growing tumor development.

This is what Esserman, Fiscalini and colleagues plan to investigate in WISDOM 2.0, which is 1 year into recruitment with 16,000 women registered and 12,000 women enrolled. With WISDOM 2.0, researchers plan to update risk assessments, enhance genetic results and expand participant enrollment to include women starting at age 30 years.

Esserman said researchers are working on a polygenic risk score specifically for faster-growing tumors and a tool to improve breast density assessment.

“Women at high risk and with very high [breast] density undergo an MRI, but data do not support every women with these risk factors receiving an MRI, and certainly not an ultrasound,” Esserman said. “Ultrasound is not a good screening tool. It increases the yield by maybe 1% with a huge risk for false positives and is a lot of money, time and effort. We want everyone’s time and effort going to the things that make the most sense.”

In addition to working on WISDOM 2.0, Esserman is involved in a new interdisciplinary breast cancer conference, RISE UP for Breast Cancer, held Nov. 1 to 3 in San Francisco. The conference focused on reimaging breast cancer prevention and treatment, Esserman said.

“We need to do better,” Esserman said. “We need to understand breast cancer, starting with an understanding of where we are, what the treatments are, prevention and then how are we rethinking all the hormonal interventions that we prescribe over a woman’s lifetime. How can we reduce risk and reimagine our approach?”

References:

• The WISDOM Study. www.thewisdomstudy.org/. Accessed Nov. 1, 2024.
• University of California, San Francisco. RISE UP for Breast Cancer. https://riseup.ucsf.edu/. Accessed Nov. 1, 2024.

For more information:

Laura J. Esserman, MD, MBA, can be reached at laura.esserman@ucsf.edu.

Allison Stover Fiscalini, MPH, can be reached at allison.stoverfiscalini@ucsf.edu.