Breast Cancer Coverage from Every Angle

Can Tumor Marker Help to Predict Response to HER2 Inhibition in Breast Cancer?

By: Kayci Reyer
Posted: Tuesday, August 3, 2021

According to research presented in Nature Communications, inhibition of the tyrosine kinase receptor HER2 may help to overcome endocrine treatment resistance, which occurs in approximately 30% of patients with estrogen receptor–positive breast cancer. A defect in the mismatch repair function, specifically the loss of MLH1/PMS2, may be a strong predictive biomarker for endocrine treatment sensitivity in some patients with estrogen receptor–positive/HER2-negative disease.

“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,” noted Svasti Haricharan, PhD, of Sanford Burnham Prebys Medical Discovery Institute in California, in an institutional press release.

Some patients who are first diagnosed with this type of breast cancer eventually experience a HER2-positive conversion following treatment with endocrine therapy. When activated, HER2 promotes rapid disease proliferation and endocrine therapy resistance. This activation may be preventable in patients with MLH1/PMS2 activity, detectable through genetic testing. These genes are part of the biologic mismatch repair function but also suppress HER2; their loss makes HER2 activation possible once endocrine therapy is introduced.

By testing patients with estrogen receptor–positive/HER2-negative breast cancer for MLH1/PMS2 activity, treatment providers may be able to provide early targeted endocrine therapy without triggering HER2 activation and disease proliferation.

Disclosure: For full disclosures of the study authors, visit

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