HER-2 ultra-low breast cancer: exploring the clinicopathological features and prognosis in a retrospective study.
Frontiers in oncology
Objective:To explore the clinicopathological features of patients with ultra-low expression of human epidermal growth factor 2 (HER-2) in breast cancer and its impact on prognosis. Methods:Data from 1024 patients with primary breast cancer having HER-2 ultra-low expression from January 01, 2018, to December 31, 2018, were collected and analyzed retrospectively. The clinicopathological features and prognosis were compared using a chi-squared test or Fisher exact probability method. COX regression analysis and log-rank test were used to explore the factors related to the postoperative 5-year survival rate. All analytical data were defined as statistically significant ( < 0.05). Results:Overall survival (OS) was higher in the HER-2 ultra-low group compared to the low expression group ( = 0.022). The tumor diameter, lymph node metastasis (LNM), and Ki67 expression were factors affecting DFS in the HER-2 ultra-low expression group ( < 0.05). The tumor diameter and LNM were risk factors affecting the OS ( < 0.05) in the HER-2 ultra-low expression group. LNM and Ki67 expression were risk factors affecting DFS ( < 0.05) in the HER-2 low expression group. LNM was considered an independent risk factor affecting OS ( < 0.05). Conclusion:Breast cancer with HER-2 ultra-low expression has differences in the clinicopathological features. Breast cancer with HER-2 low expression is more aggressive and has a worse prognosis. This study provides a reference to consider in the treatment of HER-2-low and -ultra-low expression breast cancer.
10.3389/fonc.2023.1210314
[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].
Zhonghua bing li xue za zhi = Chinese journal of pathology
To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 μltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (=0.001). Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.
10.3760/cma.j.cn112151-20240125-00063
Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes.
International journal of molecular sciences
HER2-low and ultra-low breast cancer (BC) have been recently proposed as new subcategories of HER2 BC, supporting a re-consideration of immunohistochemical negative scores of 0, 1+ and the 2+/in situ hybridization (ISH) negative phenotype. In the present review, we outline the criteria needed to exactly distinguish HER2-low and ultra-low BC. Recent clinical trials have demonstrated significant clinical benefits of novel HER2 directing antibody-drug conjugates (ADCs) in treating these groups of tumors. In particular, trastuzumab-deruxtecan (T-Dxd), a HER2-directing ADC, has been recently approved by the US Food and Drug Administration as the first targeted therapy to treat HER2-low BC. Furthermore, ongoing trials, such as the DESTINY-Breast06 trial, are currently evaluating ADCs in patients with HER2-ultra low BC. Finally, we hope that new guidelines may help to codify HER2-low and ultra-low BC, increasing our knowledge of tumor biology and improving a targetable new therapeutical treatment.
10.3390/ijms241612795
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline Update.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE:To update ASCO-College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. METHODS:An Update Panel conducted a systematic literature review to identify signals for updating recommendations. RESULTS:The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations. RECOMMENDATIONS:The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. DISCUSSION:HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences.Additional information is available at www.asco.org/breast-cancer-guidelines.
10.1200/JCO.22.02864