Study provides new insight into how low HER2 tumors may evolve in breast cancer patients


The finding that breast tumors may evolve to express low HER2 may potentially expand the number of patients who may benefit from new research agents, typically new antibody-drug conjugate therapies, who are currently in clinical trials for low HER2 tumors. .

The first study of this type that explores how breast cancers change from primary tumor to recurrent has revealed that almost 30% of breast cancer patients become human epidermal growth factor (HER) receptor status of 2 o under a. Specifically, the study found that 14% of triple-negative breast cancers with HER2-negative expression (also called HER2-0) in the primary tumor converted to low HER2-expression in the recurrent tumor possibly offer an option to this type. of hardness. to treat tumors.

Traditionally, breast cancers are classified into: hormone receptor positive (HR +) / HER 2-negative (also known as luminal), HER2 positive or triple negative (negative for estrogen receptors, progesterone receptors and excess protein HER2). HER2-low refers to HER2-negative tumors with low HER2 biomarker expression. Approximately half of breast cancers classified as HER2-negative exhibit low HER2 expression.

Presenting the conclusions of this year’s ESMO Virtual Breast Cancer Congress, Dr. Federica Miglietta, Faculty of Oncology, University of Padua, Italy.

The results provide a whole new insight into how low HER2 tumors could evolve as a subgroup, challenging the current dichotomy between HER2-positive and HER2-negative breast cancer. Our results underscore the importance of retesting HER2 expression in tumor relapse, as it could provide the option of new therapeutic opportunities, currently in a trial, and hopefully in the near future, in the clinic. “

Dra. Federica Miglietta, Faculty of Oncology, University of Padua, Italy

There are several ongoing clinical trials with low-grade HER2 breast cancer.

In total, 29% of recurrent breast cancer biopsies showed conversion from low HER2 expression. In primary tumors and relapsed tumors, low HER2 expression was observed in 34% and 38% of tumors, respectively. A total of 15% of HER2-negative tumors switched to HER2-low tumors and 14% of HER2-low tumors switched to HER2-negative.

The study also confirmed that low HER2 expression was more common in HR + / HER2 negative tumors compared to triple negative tumors (47% vs 36% in primary tumor samples, 54% vs 36% in relapse samples) . In addition, the change from HER2-negative to HER2-low in primary to recurrent tumors was 21% versus 14% in luminal and triple negative type, respectively.

Commenting on the findings, Professor Aleix Prat, Head of Medical Oncology at Hospital Clínic de Barcelona, ​​said: “These changes in the low levels of HER2 are substantial. There could be a biological or technical justification, as there is currently no standardization of how to determine HER2 biomarker levels in metastatic biopsies, which could be biopsied from the skin, liver or bone and give different results. “

“We need to find out how HER2 status determines response to therapies: is HER2 status important in primary tumor or metastatic biopsy? Perhaps some patients have low HER2 expression in metastatic tumors and now respond when not before. it did, and that could change again over time and fall back more. “

“All of this speaks to a much greater need to biopsy metastatic tumors. It is important to note that we need to determine who will benefit from HER2-low treatments, because patients will soon ask the clinic if the test results are positive, “Prat said. .

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