HER-2 underexpression

The DCA demonstrated that the net benefit of the model was significantly greater than zero at a predicted probability of 0.764. The neural network model based on MRI features is an effective tool in predicting HER2-low breast cancer, which may facilitate clinical treatment decision-making.

Follow-up showed that HER2-low patients had the worst prognosis compared with HER2-negative (P=0.02) and HER2 positive (P=0.02) and also had the highest progression rate in TCGA cohort (P=0.02); receiver operator characteristic (ROC) model suggested HER2-low could effectively predict prognosis. HER2 expression is closely related to the TNM stage of urothelial carcinoma; HER2 three-tier assessment can effectively predict clinical prognosis of urothelial carcinoma.

P1, N=26, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

Site-specific recurrence patterns differ between HER2-low and HER2-0 patients. However, it does not support that HER2-low breast cancer is a distinct prognostic subtype.

Patients with HER2-low status exhibited intermediate and specific clinicopathological features within the HER2-negative category. In terms of prognosis, HER2-low patients showed a worsening trend compared with HER2-positive patients. This evidence implies that HER2-low status represents a distinct clinical subset, bridging the gap between the HER2-zero and HER2-positive profiles.

There is an important percentage of Hispanic/Latino individuals who would benefit from HER2-targeted therapies, even in HER2 negative cases. Additional research on the prevalence of HER2-low tumors across a wider range of Latin American countries is required to better understand the molecular epidemiology of this biomarker within the Hispanic/Latino population.

Discrepancy in the HER2 status of the metastases and of CTCs was observed in approximately one third of patients. Measuring HER2 on CTCs could potentially offer a means to longitudinally monitor HER2 status during therapy and simultaneously address challenges such as tumor heterogeneity. Therefore, the predictive value of HER2 on CTCs should be further investigated in clinical trials.

Quantitative parameters from intravoxel incoherent movement imaging and dynamic contrast enhancement MRI can predict different HER2 expressions in breast cancer from different perspectives, with implications for therapy.

Studies evaluating ADCs (trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), MRG002, and RC48-ADC) in patients with HER2-low a/mBC were included. Future studies should focus on bringing ADCs into earlier lines of therapy in this population. This study was registered in PROSPERO (CRD42024452962).

RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

At the same time, it is recommended to reevaluate the HER2 status in the event of disease recurrence or metastasis, even if the previous test result is HER2-0. On the other hand, it is recommended to further improve and optimize detection techniques and methods, reduce false negatives and false positives, and enhance the sensitivity and specificity of detection.

The APIS kit accurately measures HER2/ERBB2 expression. The findings indicate that relying solely on IHC stratification may not be sufficient to predict responses to novel anti-HER2 treatments, like T-Dxd. By leveraging the dynamic range of RNA expression, a ΔCt semi-quantitative scale using additional cut-offs has been developed to enhance the stratification of ERBB2 mRNA expression.

P2, N=180, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.

For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

P2, N=66, Recruiting, Henan Cancer Hospital | Trial primary completion date: May 2024 --> Dec 2024

BRCA mutation and PD-L1 positivity are higher in HER2-negative TNBC. Our study revealed that HER2-negative breast cancer has more basal-like clinicopathologic features, while HER2 Low TNBC has non-basal features.

However, this may be due to lack of sensitivity of IHC, which is currently used to select patients for T-DXd treatment, despite major diagnostic challenges... ERBB2del are frequent events in ER+/HER2- BC that are characterized by low ERBB2 mRNA levels, and are associated with TP53del, higher proliferation and immunogenicity, lower ER signaling and HER2 protein expression, and decreased OS in the metastatic setting.

Linearity testing, where the cell lines were spiked in 7.5mL blood, showed high levels of reproducibility across the clinical range (1000 cells to 0) with an R2 = 0.99. The CELLSEARCH® CTC-HER2 Low test meets a critical clinical need that breast cancer patients, positive or classified as negative from a tissue biopsy, in need of a current evaluation of their metastatic breast cancer HER2 status, through any line of treatment, can do so from one blood draw using a test that can detect HER2 expression to very low levels.

Our findings add valuable information to the current understanding of the HER2 spectrum in the male breast cancer, including frequency distribution and molecular characterization. With some exceptions, HER2-low, ultra-low and null breast cancer in men shared genomic features, suggesting that the disease biology may not be different across the spectrum of what historically has been considered HER2-negative disease. Interestingly, HER2 ultra-low, HER2-low and HER2-null had differential tumor immune microenvironment that warrant further exploration.

TIL levels are higher in early-stage HR-positive breast carcinomas with a high recurrence risk. These tumors also harbor targetable genomic alterations, suggesting that TIL measurement and genomic profiling could enhance risk stratification and identify patients who might benefit from targeted therapies. Her-2 low expression in high-risk patients provides a consideration for including novel ADC therapies in this subset of patients.

Our findings demonstrated a significant influence of HER2-low expression on the response to neoadjuvant chemotherapy among patients with hormone-positive HER2-low breast cancer within the studied cohort. Further studies are needed to evaluate the influence of hormonal expression on the response rate to NACT in the HER2-low patients in our population.

The radiomic signature and tumor descriptors from gray-scale US may predict distinct HER2 expressions of breast cancers with therapeutic implications.

Our study indicates that HER2-low status had no impact on pCR or DFS.

Kaplan-Meier survival curves showed that menstrual status, N staging, T staging, TNM staging, and pCR status affected the prognosis of HER2-low breast cancer patients (p < 0.05). HER2-low breast cancer exhibits distinct biological behaviors, suggesting personalized treatment approaches.

Furthermore, the 6-year OS rates were 94.2% (95% confidence interval (CI) 83.1-98.1), 88.7% (74.4-95.2) and 78.1% (65.4-86.6) for patients with stable, once and none HER2-low expression, respectively (adjusted HR, 0.514 &lsqb;95%CI, 0.294-0.897], p = .019). Our study first indicated in patients across all expression levels of HER2 that stable or at least once HER2-low status may confer favourable attributes including less malignant biological behaviour and long-term survival benefit for breast cancer receiving neoadjuvant therapy.

The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram. The nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

Compared with those with high ERBB2 expression, tissues with low ERBB2 expression displayed greater immunogenicity and enrichment of immune pathways, particularly those related to B cells. These findings suggest that patients with low ERBB2 expression are likely to benefit from immunotherapy, especially B-cell-related immunotherapy.

P1, N=26, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

After HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.

The overall consistency of HER2 expression between antibodies of different clone numbers was high, but the consistency of detecting HER2 low and ultra-low expression cases was poor, and there were differences in the detection rates, which still need to be validated by more subsequent studies.

The APIS Breast Cancer Subtyping Kit accurately detects HER2/ERBB2 expression. The findings suggest that relying solely on IHC categorisation may not suffice for predicting response to novel anti-HER2 treatments. Utilising additional cut-offs could enhance the stratification of ERBB2 mRNA expression, distinguishing a ‘HER2- low’ group.

This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

No abstract available

The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (P<0.05), and SLX4 gene was only mutated in HER2 1+ group. There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

A high proportion of HER2-low expressors demonstrated HER2-CTC positivity. Monitoring CTC-HER2 status may offer prognostic value in patients with IBC.

Local vs central HER2 agreement by standardized IHC techniques decreased for HER2-low compared to HER2 status. Monoclonal HercepTest proved higher agreement with gold standard than polyclonal HercepTest in terms of HER2 status and HER2-low BC identification, especially for 1+ and 2+ IHC cases. This highlights the need for standardized HER2 testing review, particularly when evaluating potential benefits of novel therapies for HER2-low BC patients.

Significant associations between ERBB2 alterations and HER2 low-expressing tumors were observed. High prevalence of ERBB2 alterations was observed in some uncommonly tested tumors. Median OS of HER2 low-expressors was better than non-expressors in this heterogenous group.

Early-stage HR-positive breast carcinomas have low TIL levels regardless of the recurrence risk, molecular subtype, and HER2- low status. These cancers are markedly enriched by HER2-low phenotype, which might have therapeutic implications due to the recently approved anti-HER2 antibody-drug conjugate.

In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

This has provoked many discussions on HER2-low breast cancer, such as quality control prior to HER2-low expression detection, the latest progress of tumor heterogeneity, and the application of AI. In this paper, we discuss the latest testing guidelines and advances on HER2-low breast cancer, aiming to standardize and improve the pathological testing of HER2-low breast cancer.

This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease.