Key Points
• Conclusion/Relevance: “The prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk …. These novel findings may point on a new prognostic feature of early-stage, high genomic risk luminal disease.”
• Recent research indicates that human epidermal growth factor receptor 2 (HER2)-low breast cancer may be its own clinical entity. In the current retrospective study, researchers compared disease characteristics and outcomes between HER2-low vs HER2-0 among 608 patients with estrogen receptor (ER) positive, early-stage breast cancer. These patients had previously received an Oncotype DX test between 2005 and 2012, and were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0.
• High risk (RS > 25) HER2-low disease was related to favorable outcomes vs HER2-0, whereas outcomes for low genomic risk (RS < 25) HER2-low vs HER2-0 were comparable.
• The lobular subtype was more frequent in HER2-0 vs HER2 low disease.
• “While HER2-positive disease is chemo-sensitive, whether HER2-low expression is predictive to chemotherapy is unclear. Consistent with guidelines, most women with high genomic risk received adjuvant chemotherapy in this cohort. As only few women with high genomic risk did not receive chemotherapy, the conclusions that can be drawn from the predictive role of HER2-low in this population are limited. However, the trend for favorable outcomes was noted in HER-low disease with high genomic score both is women who were treated with chemotherapy and in women who forgo chemotherapy,” wrote the authors.
• Limitations of the current study include the fact that HER2 immunohistochemistry interpretation is observer dependent, with varying assessments of tumor samples. The data in this study come from a single center and are retrospective, thus bias may play a role. Additionally, data on the adherence and duration of treatment, along with complete data on the type of endocrine therapy during all periods were not noted. Lastly, because the number of women with high genomic risk who were not treated with chemotherapy was small, it remains to be elucidated whether HER2-low is and independent prognostic factor or is correlated with more chemo-sensitive disease vs HER2-0.