April 23, 2024

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Tumor markers may help on breast cancer resistant to endocrine therapy

Nat Commun: Special tumor biomarkers may help overcome breast cancer that is resistant to endocrine therapy


Tumor markers may help on breast cancer resistant to endocrine therapy.  The clinical trials of pan-HER inhibitors in ER+/HER2- patients disappointed researchers. This may be due to the lack of corresponding predictive biomarkers.


In  United States, approximately 30% of ER+ breast cancer patients will develop resistance to endocrine therapy, and it will lead to the death of 40,000 patients each year. Preclinical studies have revealed that the growth factor receptor named HER2 is activated during the development of endocrine therapy tolerance. However, clinical trials of pan-HER inhibitors in ER+/HER2- patients have disappointed researchers. Perhaps it is due to the lack of corresponding predictive biomarkers.


Tumor markers may help on breast cancer resistant to endocrine therapy

Image source: https://www.nature.com/articles/s41467-021-23271-0


A few days ago, in a research report titled “Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer” published in the international journal Nature Communications, scientists from Sanford Burnham Prebys Medical Discovery Institute and other institutions identified through research A special tumor marker has been developed that may help predict which breast cancer patients will experience tolerance to endocrine therapy. The research also proposes a new method to select patients who can target HER2 therapy. HER2 is a special protein that can promote the growth of cancer cells, which can help prevent patients from recurring disease or progressing to endocrine-sensitive diseases.


About 80% of breast tumors are estrogen receptor positive (ER+). For decades, researchers have used anti-estrogen (endocrine) therapy to treat this cancer to reduce the level of estrogen in the patient’s body and help slow down The growth of tumors. About 20% of breast cancers are also HER2+ at the time of diagnosis, and these tumors tend to be more aggressive and grow rapidly because HER2 is a receptor that, when activated, promotes the rapid growth of breast cancer cells.


Researcher Dr. Svasti Haricharan said that we know that some patients are initially diagnosed with ER-positive or HER2-negative breast tumors, but their tumors will become HER2-positive (HER2+) after receiving endocrine therapy. Unfortunately, this will release the adverse effects of HER2, patients will also develop tolerance to endocrine therapy, and will lead to disease recurrence, metastasis and even patient death.


Since traditional endocrine therapy does not help these patients, in this study, the researchers focused on analyzing two genes that affect HER2 activity, namely MLH1 and PMS2 genes. These genes are part of the biological system that repairs DNA errors, but It plays a key role in inhibiting the activity of HER2. When these genes are turned off, HER2 will be activated, and as long as the patient receives standard endocrine therapy, it will also be activated.


The researchers said that, fortunately, screenings for colorectal cancer and endometrial cancer now have routine MLH1 and PMS2 gene activity tests. If we can transition these tests to newly diagnosed breast cancer cases, we will be able to identify which patients will benefit from early HER2 targeted therapy, basically shutting it down before HER2 activity begins. .



The level of HER2 RNA in ER+ and HER2- breast cancer patients with MutL-tumor will increase and is directly related to a significantly poorer disease-specific prognosis.

Tumor markers may help on breast cancer resistant to endocrine therapy

Image source: Punturi, N.B., et al. Nat Commun 12, 2940 (2021). doi: 10.1038/s41467-021-23271-0


According to estimates by the National Cancer Institute, 281,550 women in the United States will be diagnosed with breast cancer in 2021, and 43,600 women will die from the disease. Some women whose MLH1 and PMS2 gene expression levels are low or missing may even face a greater risk of death. The results of this study may be expected to provide patients with the most appropriate therapeutic methods. Nowadays, there are many excellent drugs that can treat breast cancer, including drugs that target HER2. It is not so much looking for new drugs as it is to choose existing suitable drugs, and the research work in this article is directed towards this. A step forward in the direction.


In summary, the results of this article reveal that MutL deletion may be used as a new class of predictive sensitivity markers, which may indicate endocrine interventions and HER inhibitors in the treatment of ER+/HER2- breasts that are resistant to endocrine therapy. The effect of cancer patients.


(source:internet, reference only)

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