Study: Breast Tumors Evolving to HER2-Low May Provide Broader Therapeutic Options

Data presented at the 2021 ESMO Breast Cancer Virtual Congress showed 29% of recurrent breast cancer biopsies showed conversion either from, or to, HER2-low expression.

Nearly 30% of patients with breast cancer convert from, or to, human epidermal growth factor receptor 2 (HER2)-low status, according to a study presented at the ESMO Breast Cancer Virtual Congress 2021 and published in Annals of Oncology. The finding that breast tumors can evolve to express low HER2 potentially widens the number of patients who can benefit from new investigational agents—specifically, novel antibody-drug conjugate therapies—that are currently in clinical trials for HER2-low tumors.

Traditionally, breast cancers are categorized as hormone receptor positive (HR+)/HER 2-negative, 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.

“The [study] 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 Federica Miglietta in a press release. “Our findings stress the importance of re-testing 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”

According to the study authors, 29% of recurrent breast cancer biopsies showed conversion either from, or to, HER2-low expression. In primary tumors and relapse 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% HER2-low switched to HER2-negative.

The study also found that HER2-low expression was more frequent in HR+/HER2-negative tumors compared to triple negative tumors (47% vs 36% on primary tumor samples, 54% vs 36% on relapse samples). Additionally, the switch from HER2-negative to HER2-low in primary to recurrent tumors was 21% vs 14% in HR+/HER2-negative and triple negative, respectively

“These changes on HER2-low levels are substantial,” said Aleix Prat, MD, PhD, in the release. “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. 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."


Switch of breast tumors to HER2-low in recurrence may provide greater therapeutic options [news release]. EurekAlert; May 8, 2021. Accessed May 11, 2021.