The finding that breast tumors can evolve to express low HER2 potentially increases the number of patients who can benefit from new investigational agents, typically novel antibody-drug conjugate therapies, that are currently in clinical trials for HER2-low tumors. This research was presented by Federica Miglietta, MD, and colleagues at the ESMO Breast Cancer Virtual Congress 2021 (Abstract 4MO_PR).
The first study of its kind exploring how breast cancers change from the primary to the recurrent tumor has revealed that nearly 30% of patients with breast cancer convert from, or to, HER2-low status. Specifically, the study found that 14% of triple-negative breast cancers with HER2-negative expression in the primary tumor converted to HER2-low expression in the recurrent tumor—possibly offering an option in these hard-to-treat cases.
Traditionally, breast cancers are categorized as hormone receptor–positive/HER2-negative (also known as luminal-like), HER2-positive, or triple-negative (negative for estrogen receptors, progesterone receptors, and excess HER2 protein). HER2-low refers to HER2-negative tumors with low HER2 biomarker expression. About half of breast cancers classified as HER2-negative show low HER2 expression.
Federica Miglietta, MD
“The results provide a whole new insight on how HER2-low tumors might evolve as a subgroup, possibly challenging the current dichotomy between HER2-positive and HER2-negative breast cancer,” said Dr. Miglietta. “Our findings stress the importance of retesting HER2 expression on tumor relapse, since it might provide the option of new therapeutic opportunities, currently in a trial, and hopefully in the near future, in the clinic.”
Several clinical trials are ongoing in HER2-low breast cancer.
More on the Results
In total, 29% of recurrent breast cancer biopsies showed conversion either from, or to, HER2-low expression. In primary tumors and relapsed tumors, HER2-low expression was seen in 34% and 38% of tumors, respectively. A total of 15% HER2-negative tumors switched to HER2-low tumors, and 14% of HER2-low tumors switched to HER2-negative.
The study also confirmed that HER2-low expression was more frequent in hormone receptor–positive/HER2-negative tumors compared to triple-negative tumors (47% vs 36% on primary tumor samples, 54% vs 36% on relapse samples). Plus, the switch from HER2-negative to HER2-low in primary to recurrent tumors was 21% vs 14% in luminal-like and triple-negative, respectively.
Commentary
Commenting on the findings, Aleix Prat, MD, PhD, Head of Medical Oncology at the Hospital Clínic of Barcelona, said, “These changes on HER2-low levels are substantial. There could be a biological rationale for this, or a technical one, given that there is currently no standardization of how to determine levels of the HER2 biomarker in metastatic biopsies, which could be biopsied from skin, liver, or bone and give different results.”
Aleix Prat, MD, PhD
“We need to work out how the HER2 status determines response to therapies—is it the HER2 status in the primary tumor or in the metastatic biopsy that is important? Maybe some patients have HER2-low expression in metastatic tumors and now respond when they didn’t previously, and this might change again over time and further relapses.”
“This all speaks to a much greater need to biopsy metastatic tumors. Importantly, we need to determine who will benefit from treatments for HER2-low [disease], because patients will be asking about this in the clinic soon if trial results are positive,” said Dr. Prat.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
