Hormone receptor-positive (HR+) breast cancer is a type of breast cancer that contains hormone receptors that pick up estrogen or progesterone signals that promote cell growth, including the growth of cancer cells. One of the most effective treatments for HR+ breast cancer is endocrine therapy, which stops or interferes with the body’s ability to produce hormones. While many patients respond favorably to endocrine therapy, approximately 20-25% of patients develop resistance, and the cancer recurs and spreads.
In a recent phase II clinical trial, MCW Cancer Center investigators set out to uncover why endocrine therapy works for some patients and not others. “Endocrine therapy is routinely used in an adjuvant setting (after a tumor is removed) for 5-10 years and it helps improve patient outcomes,” said Lubna Chaudhary, MD, associate professor of medicine, hematology and oncology.
“Our study examined the effects of short-term neoadjuvant endocrine therapy (NET), which is typically administered before surgery to reduce tumor size. This enabled us to measure changes in the tumor microenvironment early on, to identify how cancer cells evade endocrine therapy,” said Dr. Chaudhary. “HER+/HER2- breast cancer is one of the most common subtypes of breast cancer. These are important findings with potentially practice changing implications given the availability of HER2-directed drugs.”
The trial included 37 patients with early-stage HR+/HER2- breast cancer. The primary objective, notes Chaudhary, was to study changes in the human epidermal growth factor receptor (HER1-4) family of proteins with short-term NET to identify tumors that may be using the HER2 pathway to overcome endocrine treatment. Investigators found that 17 of 35 patients (48.6%) with evaluable tumors had tumors with a significant increase in HER2 receptors approximately 4 weeks after treatment. While there was no significant reduction in tumor size with this short-term treatment, there was a significant reduction in cell division within tumors assessed by measuring tumor proliferation protein Ki67. “HER+/HER2- breast cancer is one of the most common subtypes of breast cancer. These are important findings with potentially practice changing implications given the availability of HER2-directed drugs,” said Dr. Chaudhary.
Advanced tumor testing and protein measurements were performed by MCW’s Julie Jorns, MD, and Yunguang Sun, MD, PhD. Using multiplex immunofluorescence technology available through the MCW Cancer Center’s Biorepository and Tissue Analytics Shared Resource, they were able to stain six biomarkers within a single tissue section to analyze and map what was happening at the cellular level. “This advancement facilitates a more precise and sophisticated approach to biomarker-based phenotyping which helps predict how patients will respond to different therapies so we can tailor their treatments accordingly,” notes Sun.
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