March 4, 2026 | Austin, Minn. — In 2026, more than 321,000 women will be diagnosed with invasive breast cancer, the American Cancer Society predicts. Because there are multiple subtypes of breast cancer that use different tactics to grow and spread, it’s essential that continued research opens doors for patients to have access to the right kinds of treatment for the right kind of cancer.
Executive Director Robert Clarke, PhD, DSc, at The Hormel Institute, University of Minnesota, is one of several researchers who contributed to a recent study investigating a new possible approach to treating a breast cancer subtype called estrogen receptor-positive (ER+) luminal breast cancer. They made new discoveries about why therapy resistance may happen in some cases of breast cancer — as well as a promising new combination therapy treatment method that, with further research, may help improve breast cancer outcomes.
What is estrogen receptor-positive luminal breast cancer?
There are many different ways that cancers, including different types of breast cancer, can grow and spread in the body. To classify them, medical professionals track different markers, such as hormone receptors or their molecular subtypes (including the luminal A and B subtypes studied here). These classifications help them understand what may be fueling cancer growth in a specific case and select a treatment method that will have the best odds of effectively targeting the cancer.
In this study, published in the scientific journal Science Translational Medicine, Dr. Clarke and researchers investigated whether the use of immunotherapy in combination with additional treatment could be effective in patients with ER+ luminal breast cancer.
In ER+ breast cancer, cancer cells have receptors that bind to estrogen hormones that allow them to circulate throughout the body and accelerate cancer progression. When treating breast cancers with an ER+ classification, therapy that targets estrogen receptors (ER-targeted therapy) is often successful. However, therapy resistance can become a treatment obstacle for some of these patients, leading to poorer prognosis. Considering 75% of patients with breast cancer are diagnosed with the ER+ subtype, as their paper notes, there is a substantial, ongoing need to develop more effective treatment options in this area.
What researchers discovered
Therapy resistance for ER+ breast cancer is often aided by a specific type of immune cell, which the cancer cells enlist to act as their protective army. The researchers explored a method that could block these cells, rendering therapy more effective.
In their experiments, they used a triple-therapy approach using low-dose tamoxifen (a hormone therapy drug commonly used in breast cancer treatments), as well as antibodies to block the function of both DLL1 and PD-L1. The protein PD-L1, found in this immune cell, and the molecule DLL1, which draws the immune cells into tumors to help guard its own cancer cells, are commonly present in ER+ breast cancer patients who experience therapy resistance.
In the research models and patient-derived explants (tumor samples) they tested, researchers found this combination therapy:
- Shrank tumors
- Reduced cancer stem cell levels
- Trained immune responses to more effectively combat cancer growth
What’s next
The researchers’ findings suggest that this is a promising avenue for continued exploration to improve breast cancer treatment outcomes and save lives. More research will be needed before this treatment method can make its way into the clinic.
“As researchers, we seek discoveries that can give patients with cancer more options, more time, and more answers to their questions. Taking all the steps to confirm safety and efficacy for any new treatment method is a top priority,” Dr. Clarke said. “More research will be needed to determine if this treatment avenue could help improve outcomes for ER+ luminal breast cancer patients. We’re encouraged by what we’ve learned so far.”
You can read the paper here: https://www.science.org/doi/10.1126/scitranslmed.adr6207
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ABOUT THE HORMEL INSTITUTE
Founded in 1942 by Jay C. Hormel and The Hormel Foundation, The Hormel Institute, University of Minnesota, makes scientific advancements that enhance wellbeing and extend human life. For more than 80 years, we have pursued our mission to conduct research and provide education in the biological sciences with applications in medicine and agriculture. A part of the University of Minnesota's Research and Innovation Office, The Hormel Institute partners with the region's leading biomedical research facilities, including Mayo Clinic.