For thousands of women diagnosed with estrogen receptor-positive (ER+) breast cancer, endocrine therapy is a lifeline that blocks or reduces estrogen to help prevent recurrence. But for up to 25% of patients, the tumor finds a way to resist treatment, coming back stronger and more difficult to treat. Understanding why this happens is critical to improving survival rates and developing more effective, personalized treatments.
Lubna Chaudhary, MD, Associate Professor of Hematology and Oncology, is unlocking these insights with newly awarded Our Patient Project (OPP) funding. Supported by $650,000 over four years, her study, Molecular Analyses to Predict Pathways of Endocrine Resistance Following Short-Term Neoadjuvant Endocrine Treatment in Patients with Hormone Receptor-Positive HER2-negative Breast Cancer (MAPPER), aims to identify biological markers that predict endocrine resistance. By tracking how tumors respond to short-term neoadjuvant endocrine treatment (NET), the study will lay the foundation for more personalized treatment strategies, ensuring patients in our community can receive therapies suited to their cancer’s unique biology.
“Endocrine therapy works well for many patients, but for some, the cancer finds a way to resist it. By identifying the pathways driving resistance early, we can intervene before the disease has a chance to return,” said Dr. Chaudhary.
Cracking the Code on Endocrine Resistance
ER+ breast cancer accounts for nearly 70% of all cases and is often considered less aggressive than other types. However, recurrence remains a major challenge and can happen years after remission. Some tumors are resistant from the start while others adapt over time, finding new ways to survive. One key factor in this resistance is HER2, a protein linked to aggressive tumor growth.
Past MCW research suggests that endocrine therapy itself may contribute to this resistance. In a phase 2 trial, Dr. Chaudhary and her team found that nearly half of patients receiving short-term NET saw an increase in HER2 expression, despite initially testing HER2-negative. This finding highlights the need to detect resistance early to guide treatment decisions.
To address these challenges, MAPPER will enroll 100 patients with ER+/HER2-negative breast cancer, analyzing tumor samples before and after short-term NET to uncover the molecular drivers of resistance. The study focuses on two key goals:
- Identify early warning signs of resistance. By tracking changes in HER2 levels, immune markers, and tumor activity, researchers can pinpoint the first signs that a tumor is evading treatment.
- Unlock new precision medicine strategies. Understanding how tumors adapt to NET could lead to more effective therapies that stop resistance before it starts
Advancing Personalized Treatment and Expanding Access
Breast cancer treatment is not one-size-fits-all—MAPPER aims to ensure patients in our community receive the right therapies based on their tumor’s unique biology while improving clinical decision-making. However, access to precision medicine varies across Wisconsin and the country, making it difficult for some patients to receive advanced care. By generating a rich dataset, MAPPER will help shape future clinical trials and expand access to more effective, individualized treatments.
The MCW Cancer Center has long led innovative breast cancer research, from immunotherapy for aggressive tumors to uncovering how cancers evade treatment. Dr. Chaudhary’s study builds on this progress, helping to transform how clinicians approach endocrine resistance and develop therapies that could change clinical practice.
“We’re not just studying resistance—we’re working to stay ahead of it. The insights from MAPPER could be the key to keeping cancer from coming back, ensuring that every patient receives the treatment that gives them the best chance at a long and healthy future,” she said.