Editor's note: can be used as a new breast cancer typing, which has caused heated clinical debate. It is currently more supportive of its treatment typing, and there is still a lack of consistent data on prognosis guidance. Recently, a single-center study from China published in the journal Europe PMC showed that among HR-positive patients, HER2 low expression has a better 5-year DFS rate than HER2 zero expression patients.
Research Introduction
Human epidermal growth factor 2 (HER2) is low in expression of breast cancer, which is defined as immunohistochemistry is HER2 1+ or 2+ and has negative gene amplification, which accounts for a considerable proportion of all breast cancers. However, whether HER2-low-expressing breast cancer is an independent subtype remains controversial. The purpose of this study was to compare clinical pathological characteristics and survival results between HER2 zero expression (HER2-0) and HER2 low expression in patients with early breast cancer.
This study was a retrospective analysis, which included 1039 patients with HER2 expression data from a single center between 2013 and 2014, and 262 of them were excluded from subsequent analysis. The remaining patients were divided into HER2-0 group and HER2 low expression group. Each group was further subdivided into hormone receptor (HR)-positive and hormone receptor-negative subgroups. Clinical pathological features between HER2-0 and HER2-low expression groups were collected and compared. The main end points were disease-free survival (DFS) and overall survival (OS), and were analyzed by Kaplan-Meier method log-rank test, landmark analysis and Cox proportional hazard model.
A total of 777 non-HER2-positive patients were included in this analysis, of which 126, 552, 53 and 46 patients with HR-positive/HER2-0, HR-positive/HER2-0, and HR-negative/HER2-0, respectively. When paired in HR state, there was no significant difference in DFS and OS between HER2-0 and HER2 low expression groups. The landmark analysis of the set of 5-year time points showed that patients with HR-positive/HER2 low expression had better 5-year DFS than those with HR-positive/HER2-0 (p=0.0047). Low HER2 expression is an independent prognostic factor for 5-year DFS [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13-0.75, p=0.01].
Clinical pathological characteristics and prognosis of patients with low breast cancer with HER2-0 and HER2 expression are similar. Patients with HR-positive/HER2-expressing tumors with 5-year DFS tend to be better than those with HR-positive/HER2-0.
△Representative IHC images of low-expression breast cancers of HER2-0 and HER2
△Landmark analysis of DFS and OS in the HR-positive/HER2-0 and HR-negative/HER2 low-expression patients
Research discussion
Breast cancer treatment has always been at the forefront of precise treatment, and one of the representative examples is the targeted treatment for HER2-positive breast cancer. The emergence of novel ADC drugs has enabled the majority of patients with moderate HER2 expression to benefit from anti-HER2 treatment. However, it is still a long-term debate on whether HER2 low expression is an independent subtype, and there is also a lack of data on this aspect, especially in China's population data. Recently, our unit published a study on low HER2 expression in patients with metastatic breast cancer, and found that low HER2 expression was associated with better OS2.
This study compared the clinicopathological characteristics and prognosis between the HER2-0 and the HER2 low-expression groups under different HR states in patients with early breast cancer. In the long run, in the HR-positive cohort, the population of patients with low breast cancer with HER2 expression had better DFS than the HER2-0 population.
A new published study based on Chinese women with breast cancer (n=523) shows that low HER2 expression is associated with different clinical and molecular characteristics (such as low Ki-67 expression and specific types of gene mutations). The results of this study do not support the difference between HER2 low expression and HER2-0 biology . Given the conflicting results of the current study, it is not known whether HER2-low-expressing breast cancer is more invasive.
The prognosis of HER2 low expression of breast cancer is still controversial.DFS and OS between HER2-0 and HER2 low expression were analyzed in the overall population and in the HR-positive/negative subgroup. Regardless of HR, there was no significant difference in DFS and OS between HER2-0 and HER2 low expression. This result is consistent with a Japanese study7. However, a new Korean study shows that breast cancer-specific survival (BCSS) rather than OS is better in the HER2-low-expressing population, regardless of HR status. Another multicenter study showed that patients with low HER2 expression in nonmetastatic breast cancer had better relapse-free survival (RFS) and OS8.
Several restrictions should be considered when interpreting the results. First, this study is a retrospective analysis with some potential bias due to its nature. Secondly, the sample size of this study is relatively small, especially for HR-negative population. HER2 IHC2+ patients with no available FISH results were excluded in the study, which may cause patient selective bias. In addition, the lack of a central pathological review of IHC assessment of HER2 results in the results that may vary from person to person. Moreover, it is difficult for current detection technology to distinguish HER2-0 and HER2 IHC 1+9, which may weaken the credibility of this study.
In summary, this study shows that the clinicopathological characteristics between HER2-0 and HER2-low-expressing breast cancer in each HR-positive or HR-negative subgroup were basically consistent. Landmark analysis showed that patients with HR-positive/HER2 low expression had higher DFS after 5 years compared with HR-positive/HER-0 tumor patients.
▌Original link:
https://www.frontiersin.org/articles/10.3389/fonc.2022.906011/full
References
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