Breast cancer patients with low or absent MLH1 or PMS2 gene expression may have even greater risks of death.
New research has identified a tumor marker that could predict which patients with breast cancer will experience resistance to endocrine therapy, potentially offering a new approach to help select candidates for human epidermal growth factor receptor 2 (HER2)-targeting therapy.
HER2 is a protein that promotes the growth of cancer cells, according to the investigators at Sanford Burnham Prebys Medical Discovery Institute. Targeting these proteins can help avoid relapse or progression of endocrine-sensitive disease.
The majority (80%) of breast tumors are estrogen receptor (ER)-positive and are typically treated with anti-estrogen therapies to slow the cancer’s growth. Approximately 20% of breast cancers are also HER2-positive at diagnosis, and these tumors tend to be more aggressive and fast-growing. Some patients become HER2-positive over time, which can be especially detrimental according to the authors.
“We know there is a subset of patients who are initially diagnosed with ER-positive, HER2-negative breast tumors, but their tumors convert to HER2-positive after they receive endocrine therapy,” said senior study author Svasti Haricharan, PhD, an assistant professor in the Aging, Cancer, and Immuno-oncology Program at Sanford Burnham Prebys, in the press release. “Unfortunately, this unleashes the detrimental effects of HER2, and patients become resistant to endocrine therapy—resulting in relapse, metastasis, and death.”
Haricharan and her team investigated how the MLH1 and PMS2 genes impact HER2 activity. These genes are typically involved in fixing DNA errors, but they also play a vital role in suppressing HER2 activity. When these genes are turned off, the researchers found that HER2 becomes activated as soon as patients receive standard care endocrine therapy.
“Fortunately, there are tests for MLH1 and PMS2 activity that are now done routinely for colorectal and endometrial cancers,” said first author Nindo Punturi, a research assistant in Haricharan’s lab, in the press release. “If we were to transition these tests to newly diagnosed cases of breast cancer, we could identify patients who may benefit from early HER2 targeted treatment—essentially shutting the door to HER2 activity before it gets started.”
According to the press release, the National Cancer Institute estimates that 281,550 women will be diagnosed with breast cancer in the United States in 2021, and 43,600 women will eventually die from the disease. Those with low or absent MLH1 or PMS2 gene expression may have an even greater risk of death.
“Our research efforts are all about getting the right treatments to the right people as soon as possible,” Haricharan said in the press release. “With so many excellent drugs at our disposal to treat breast cancer—including those that target HER2—it’s more a matter of selecting the available, appropriate drugs than searching for new ones. This research effort is an important step in that direction.”
Tumor marker may help overcome endocrine treatment-resistant breast cancer [news release]. Sanford Burnham Prebys Medical Discovery Institute; May 19, 2021. https://www.sbpdiscovery.org/news/tumor-marker-may-help-overcome-endocrine-treatment-resistant-breast-cancer. Accessed May 24, 2021.