Investigators aim to personalize breast cancer prevention and save lives

Globally, breast cancer is the most frequently diagnosed cancer in women, affecting an estimated 2.3 million annually. In the U.S., where breast cancer has been the most frequently diagnosed cancer in women for many years, the American Cancer Society estimates that there will be over 310,000 new cases of breast cancer and more than 42,000 deaths in 2024 alone. With incidences rising, preventing and intercepting breast cancer is more important than ever.

BCRF is committed to supporting prevention research that takes a personalized approach and, launched its Precision Prevention Initiative (PPI) in 2019. Now, building on the great success of the first set of projects, BCRF is embarking on PPI’s next phase to support more bold and innovative research. Our goal: to harness the incredible power of precision medicine for prevention—tailoring strategies based on an individual’s genetics, environment, and lifestyle—and stop breast cancer before it starts.

The promise of prevention

Research has shown that breast cancer risk may be reduced by maintaining a healthy weight and avoiding weight gain; exercising; eating more fruits, vegetables, and whole grains; cutting down on meat and processed foods; limiting alcohol; and quitting smoking. However, more research is needed to truly personalize and advance prevention strategies.  

BCRF supports a wide range of related research through its annual grants program, providing sustained funding for approximately 40 projects every year, including the most promising research from the first phase of PPI. Our investigators are discovering innovative approaches to breast cancer prevention across three core pillars: assessing risk, devising risk-reducing interventions, and improving early detection. Phase two of PPI accelerates this essential research.

This initiative pursues a better understanding and assessment of breast cancer risk, well beyond inherited gene mutations in high-risk genetic susceptibility genes like BRCA1 and BRCA2, and beyond family and personal history. With a more complete picture of risk factors, researchers can give patients a more accurate personalized risk score that estimates a woman’s chance of developing breast cancer. To date, PPI-funded research has revealed genomic factors that drive progression of premalignancies to triple-negative breast cancer (TNBC) and has identified novel targets and tested drugs that block the early development of breast cancer.

Early detection improves outcomes, and researchers are seizing the opportunity to improve strategies to find breast cancer even sooner. Work from phase one of PPI has successfully used artificial intelligence (AI) to uncover hidden clues in mammograms. They also determined that AI—in combination with extensive patient data—enables clinicians to not only detect breast cancer sooner but assess future risk. This will, ultimately, help personalize effective prevention strategies. Other work leveraged state-of-the-art imaging, AI, and machine learning to identify features of breast tissue that are associated with TNBC. Researchers then used this information to develop a TNBC-specific risk score.

Building on phase one’s success

BCRF recently launched the next phase of PPI with a three-year, $10.75 million investment to support research that will once again fuel innovation and accelerate prevention. Broadly, PPI seeks to bring the impact precision treatment has had on outcomes to the prevention arena. It challenges the research community to explore multi-disciplinary approaches to answer breast cancer’s most pressing questions in less time, use novel technologies and identify new ways of examining available data, and build infrastructure, resources, and tools that will facilitate discovery for years to come.

Specifically, phase two of PPI will focus on several areas:

  • Risk assessment and stratification to inform individualized prevention and care strategies
  • Biomarkers for determining individual risk and screening schedules to prevent the disease, detect it earlier, or predict prognosis
  • Preventative interventions that go beyond prophylactic surgery

BCRF called for researchers to think outside of the box by engaging collaborators from diverse disciplines and using areas of expertise and methodologies not normally associated with prevention or cancer research. BCRF received a range of proposals—including single-investigator innovation projects to collaborative pre-clinical, translational, clinical, and intervention studies—all with the aim of preventing breast cancer in the first place.                

PPI Phase two projects

BCRF awarded four Clinical Trial or Intervention Study Grants geared toward preventing breast cancer or evaluating the effects of interventions on health-related biomedical or behavioral outcomes:

  • Dr. Andrea De Censi is testing various strategies to improvebreast cancer chemoprevention. He will build on prior studies that show dosing schedules for tamoxifen and exemestane could be shifted with comparable efficacy and without increasing side effects. He is now determining if further improvements in quality of life can be made with every-other-day tamoxifen or every-other-day exemestane.This study will open across seven clinical sites globally. Dr. De Censi anticipates that the results of the study will inform new approaches to breast cancer prevention that are better tolerated and have potential for broader uptake and impact.
  • Dr. Olivera J. Finn is bringing the immense power of vaccines into the prevention space. The idea is that vaccines for cancer prevention will prepare the immune system to see tumor antigens on a developing tumor and destroy it. Dr. Finn has been testing one such vaccine and will conduct a clinical trial to test its safety and efficacy in women diagnosed with pre-cancerous lesions prior to surgery. If the vaccine proves effective at preventing invasive breast cancer, it may provide an exciting new approach to breast cancer prevention that could replace surgery and chemotherapy.
  • In addition to her ongoing BCRF project, Dr. Seema Khan is testing personalized dosing of tamoxifen to prevent breast cancer. Her study builds on data from previous trials showing that low-dose tamoxifen is also effective for cancer prevention and that it reduces breast density, increasing the risk reduction benefit in women with dense breasts. Dr. Khan and her team will use “mammographic dense area reduction” (DAR) as an indicator of tamoxifen response. Two hundred high-risk premenopausal women will take low-dose tamoxifen and have DAR results assessed at six and 12 months. Depending on the DAR results at these time points, participants will have the option to increase the dose and continue treatment with their optimal dose for a total of 18 months. This trial will provide the first proof-of-concept for personalized dosing in cancer prevention.
  • Dr. Darren Mays is creating a counter-marketing intervention to reduce alcohol use in young women and measure its effects on alcohol use behavior and breast cancer risk beliefs. He and his team will use several tools, including AI, to create intervention content. This content will be used in a randomized clinical trial to test if it is effective for changing young women’s beliefs about breast cancer risks from alcohol use and their alcohol use behavior. Daily data, including information about participants’ alcohol use, will be collected through phones and wearable sensors. These projects stand to advance breast cancer prevention science in a bold new way.

Two Pre-Clinical Grants showing a clear path from the bench to bedside were funded, and both are poised to advance primary breast cancer prevention by integrating advanced technologies or experimental systems:

  • In addition to his ongoing BCRF research, Dr. Jack Cuzick is assessing the utility of measuring blood hormone levels to predict which women are at high risk of breast cancer and which will benefit from risk-reducing anti-estrogen drugs. Dr. Cuzick and his team will measure hormone levels in over 100,000 women at average and high risk of breast cancer and those with ductal carcinoma in situ (DCIS), a non-invasive breast cancer that may progress to invasive breast cancer. The team will determine whether blood hormone levels correlate with the participants’ risk profiles and observed outcomes.
  • Dr. Jennifer Ligibel is investigating the link between exercise, irisin, and breast cancer development. Her team has demonstrated that irisin, a substance released by muscle during exercise, slows breast cancer development. Her team will test whether exposure to irisin leads to activation of the immune system. Then, they will conduct a clinical trial in women at increased risk of breast cancer to assess levels of circulating irisin before and after a 12-week exercise program. They will evaluate the impact of exercise on circulating irisin, as well as on immune and proliferative markers. Dr. Ligibel’s projects will help to determine the mechanisms through which exercise could reduce breast cancer risk and perhaps identify new targets for drug development to prevent breast cancer.

Two Innovation Grants were awarded to investigators seeking to expand into a new area of discovery or to address an unmet need in primary breast cancer prevention. These projects demonstrated a high likelihood of moving to the translational stage:

  • Dr. Camila dos Santos is leveraging pregnancy-associated changes in breast tissue to reduce risk. Pregnancy is correlated with a decrease in breast cancer incidence. Dr. Dos Santos has found that the post-pregnancy mammary tissue has increased numbers of specific immune cells (NKT cells) and probiotics have an established role in stimulating NKT cells. Therefore, Dr. dos Santos is investigating a possible connection between milk-associated probiotics, the control of mammary NKT cells, and tumorigenesis. NKT cells influence other immune cells that, in turn, may provide a source of local vaccination associated with pregnancy-induced breast cancer protection. Dr. dos Santos is delving into this possibility as a novel breast cancer prevention strategy.
  • Dr. Alvaro Monteiro is identifying and stratifying BRCA1 and BRCA2 gene variants that confer intermediate risk of breast cancer. Dr. Monteiro will identify gene variants of intermediate risk that can be used as a point of comparison to integrate clinical and functional data for gene variant classification and risk assessment. His objective is to formally define a new category of intermediate-risk BRCA variants and delineate the spectrum of risk in variants of breast cancer susceptibility genes to, ultimately, propose clinical guidelines that improve risk-appropriate cancer prevention.

Data generated through PPI is expected to be made available to the research community to the fullest extent possible via BCRF’s Global Data Hub.

Cancer prevention is evolving quickly as emerging technologies are incorporated into all areas of precision medicine research. BCRF has long been at the vanguard of breast cancer research. Indeed, our researchers are today’s leaders in precision prevention and will continue to drive the groundbreaking advances of the future.

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