HER2-Low Status May ‘Evolve’ During Breast Cancer Recurrence

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: HER2-low status evolves over the course of disease progression in almost half of breast cancer patients, suggests Italian research reported at the ESMO Breast Cancer Virtual Congress 2021. 

Federica Miglietta, from the University of Padua in Italy, explained that while anti-HER2 agents are currently used only for HER2-positive breast cancer patients, novel antibody–drug conjugates (ADCs) targeting HER2 have shown efficacy in heavily pretreated patients with low HER2 expression. 

She presented findings for 547 patients who were diagnosed between 2007 and 2013 and had paired samples of both primary and locoregional or metastatic relapsed breast cancer available for analysis. 

Among primary tumour samples, the majority (61%) of cases were hormone receptor (HR)-positive, HER2-negative, while 25% were HER2-positive and 14% were triple-negative, with corresponding rates for the relapse samples of 54%, 24% and 22%, respectively. 

A 10% immunohistochemistry (IHC) score was used as the cutoff for HER2-positive status, but patients with HER2-negative status tissue samples were subclassified as HER2-low, defined as IHC 1+ or IHC 2+ without in situ hybridisation amplification, or as HER2-0, with an IHC score of 0, the investigator explained. 

Among patients with HER2-negative tumours, 45% had a HER2-low status in their primary sample and this was more common in patients with HR-positive than triple-negative disease (47 vs 36%). At relapse, 49% of patients had HER2-low status, which was significantly more common in HR-positive than triple-negative patients (54 vs 36%). 

Federica Miglietta noted that there was 39% discordance in HER2 status between the primary and relapse samples, with 15% of patients switching from HER2-0 to HER2-low and 14% changing from HER2-low to HER2-0. 

In addition, 5% of patients gained and 5% lost their HER2-positive status, the presenter said. 

HER2-negative patients were more likely to have discordance between their primary and relapse samples if they had a HR-positive rather than a triple-negative phenotype, affecting 45% and 37% of cases, respectively. 

“HER2-low expression is highly unstable during disease evolution, and this is mainly drive by HER2-0 cases switching to HER2-LOW and HER2-LOW cases switching to HER2-0”, summarised Federica Miglietta. 

Indeed, this was the case for 40% of HR-positive and 31% of triple-negative phenotype tumours. 

“Biopsy of locoregional relapses or distant metastases is strongly encouraged, since it may open new therapeutic opportunities in a not negligible proportion of patients and better assist in patients’ selection for novel anti-HER2 ADCs”, she recommended. 

Reference 

Miglietta F, Griguolo G, Bottosso M, et al. HER2-low breast cancer: evolution from primary breast cancer to relapse. Ann Oncol; 32:(suppl_2):S21–S36. DOI: 10.1016/annonc/annonc503