UNASSIGNED: This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe 99mTc-(HE)3ZHER2:V2, prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts.
UNASSIGNED: Affibody molecules were generated through genetic recombination. The radiochemical purity of the 99mTc-labeled HER2 affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the 99mTc-labeled affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts.
UNASSIGNED: Affibody (HE)3ZHER2:V2, generated through recombinant gene expression, was successfully labeled with 99mTc, achieving a radiochemical purity of (96.0 ± 1.7)% (n = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of 99mTc-(HE)3ZHER2:V2 in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1-3 h after intravenous injection of 99mTc-(HE)3ZHER2:V2 into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors.
UNASSIGNED: The molecular probe 99mTc-(HE)3ZHER2:V2 developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts in vivo. It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.

UNASSIGNED: The aim of this study was to determine whether mammographic and sonographic features of malignant breast lesions are correlated with tumor histologic grade, hormonal receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67 status.
UNASSIGNED: In this retrospective study, imaging and histopathological findings of 187 biopsy-proven breast cancer cases from November 2019 to February 2021 were reviewed. The Chi-square test was used to examine the potential correlation between mammographic and sonographic characteristics with histopathological features such as hormonal receptor, HER2 status, Ki-67 labeling index, and histological grade.
UNASSIGNED: We observed that microlobulated margin as well as oval/round morphology in mammograms correlate with triple-negative intrinsic subtype (P = 0.006 and P = 0.004). The presence of calcification in sonography was significantly higher in the luminal-B subtype (P = 0.002). Furthermore, ill-defined margins in mammography were significantly higher in amplified HER2 expression (P = 0.004) in the same manner as an oval/round shape in higher levels of Ki-67 (P = 0.030).
UNASSIGNED: Mammography and sonography features may reflect the biological behavior of various subtypes of breast cancer and can detect more aggressive breast cancers that can mimic benign or less malignant appearing lesions. These findings may be an excellent predictor for some subtypes like triple-negative breast cancer. Studying the range of these imaging characteristics may help in better understanding the prognosis, choosing a treatment strategy, and predicting response to treatment.

BACKGROUND: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes.
METHODS: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan-Meier analyses and Cox proportional hazards model were conducted.
RESULTS: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan-Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18-7.65; and P = 0.02).
CONCLUSIONS: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.

UNASSIGNED: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer (mCRC) patients with HER2 amplification, but are not satisfactory in cases of HER2 mutant CRCs.
UNASSIGNED: Consequently, further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2 (ERBB2) is imperative. Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes, tumor mutational burden, microsatellite instability, and programmed death ligand 1 (PD-L1) expression.
UNASSIGNED: Among 2454 CRC patients, 85 cases (3.46%) exhibited ERBB2 amplification, and 55 cases (2.24%) carried ERBB2 mutation. p.R678Q (28%), p.V8421 (24%), and p.S310F/Y (12%) were the most prevalent of the 16 detected mutation sites. In comparison to the ERBB2 altered (alt) group, KRAS/BRAF mutations were more prevalent in ERBB2 wild-type (wt) samples (ERBB2wt vs. ERBB2alt, KRAS: 50.9% vs. 25.6%, p < 0.05; BRAF: 8.5% vs. 2.3%, p < 0.05). 32.7% (18/55) of CRCs with ERBB2 mutation exhibited microsatellite instability high (MSI-H), while no cases with HER2 amplification displayed MSI-H. Mutant genes varied between ERBB2 copy number variation (CNV) and ERBB2 single nucleotide variant (SNV); TP53 alterations tended to co-occur with ERBB2 amplification (92.3%) as opposed to ERBB2 mutation (58.3%). KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases (KRAS/PIK3CA: 45.8%/31.2%) compared to ERBB2 amplification cases (KRAS/PIK3CA: 14.1%/7.7%).
UNASSIGNED: Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China. These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

BACKGROUND: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®.
METHODS: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system.
RESULTS: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1-55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022).
CONCLUSIONS: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy.

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR).
METHODS: We accessed our prospectively maintained institutional database. HER2 status was determined by immunohistochemistry and classified as null (score 0), over-expressed (3+), and low (1+ or 2+); in situ hybridization was not considered since it is not used for routine DCIS diagnostics.
RESULTS: Among 375 patients with DCIS, median age was 54 (27-88) years, with a primary tumor size < 2.5 cm in 63%, grade III in 33%, and positive hormone receptor status (HR) in 81% of cases; 71% underwent breast-conserving surgery, 34% received adjuvant endocrine and 39% radiotherapy. A total of 197 (52%) had tumors with low HER2 expression, which resulted significantly associated with grade I/II (P < .001), Ki67< 20% (P < .001), and HR-positive status (P < .001). HER2-low distribution varied from 19.61% and 50% in ER negative and ER-low (<10%) to 60% and 69% in ER high (50%-95%) and very high tumors (> 95%) (P < .001). After a median 39-month follow-up (IQR 16-65), cumulative incidences of LRR was 0.054. Among 17 patients with paired primary tumor and LRR, 5 had discordant HER2 status, with an even distribution of increased and decreased HER2 expression.
CONCLUSIONS: Low HER2 expression in DCIS is associated with features of reduced aggressiveness. Importantly, changes in HER2 expression may occur prompting retesting in recurrent cases, in line with observations in invasive breast cancer.

BACKGROUND: TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) is the preferred neoadjuvant therapy regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no consensus exists regarding whether specific populations may be exempt from carboplatin, allowing for de-escalation to the THP (taxane + trastuzumab + pertuzumab) regimen. Additionally, the optimal number of cycles for neoadjuvant THP remains unclear. We compared the efficacy and safety of neoadjuvant TCbHP and THP regimens, providing clinicians with a nuanced perspective to guide their treatment regimen selection.
METHODS: This multicenter real-world study included patients with HER2-positive breast cancer undergoing neoadjuvant TCbHP or THP between March 2019 and February 2023. Efficacy was assessed through the pathological complete response (pCR) rate, while safety was evaluated through monitoring adverse events.
RESULTS: Among 220 patients, 103 received 6 cycles of TCbHP (TCbHP×6), 83 received 6 cycles of THP (THP×6), and 34 received 4 cycles of THP (THP×4). The TCbHP×6 cohort exhibited a 66% pCR rate compared with 53% in the THP×6 cohort (P = 0.072). Subgroup analysis revealed that in patients aged ≤ 50 years, those with hormone receptor (HR)-negative status, and those with clinical stage T2, the pCR rate of the TCbHP×6 regimen was significantly higher than the THP×6 regimen (P < 0.05). The TCbHP×6 cohort reported higher frequencies of any-grade adverse events (99% versus 86.7%) and grade 3-4 events (49.5% versus 12%) than the THP×6 cohort. Propensity score matching identified 27 patient pairs between the THP×6 and THP×4 cohorts, indicating a significantly higher pCR rate for the THP×6 regimen than the THP×4 regimen (63% versus 29.6%, P = 0.029).
CONCLUSIONS: The TCbHP×6 regimen is favored for individuals aged ≤ 50 years and those aged > 50, ≤60 years with HR-negative status or clinical stage T2-4. For patients in compromised general condition or lacking the specified indications, the THP×6 regimen emerges as a lower-toxicity alternative with satisfactory efficacy. To ensure treatment efficacy, a minimum of 6 cycles of neoadjuvant THP is required.

Recent studies show increased expression of human epidermal growth factor receptor 2 (HER2) in cervical cancer, but the efficacy of anti-HER2 therapy remains under-researched. Here, we present a case of recurrent HER2-positive serous carcinoma, presumably arising in the cervix, diagnosed by comprehensive genomic profiling, which responded to trastuzumab. The patient underwent a radical hysterectomy with concurrent adjuvant chemoradiotherapy. One year after surgery, the patient experienced recurrence (multiple lymph node metastases). She underwent chemotherapy and subsequent comprehensive genomic profiling, which revealed HER2 positivity. Despite treatment, the lymph node and peritoneal metastases progressed. Therefore, combination chemotherapy with paclitaxel and trastuzumab was initiated. Subsequently, the patient\'s clinical symptoms improved considerably, and good health was maintained for 8 months. This report highlights the importance of comprehensive genomic profiling and targeted therapies when standard treatments fail.

OBJECTIVE: While human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma-especially in the p53 aberrant type- conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression.
METHODS: Immunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive.
RESULTS: Of the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p < 0.001) and OS (p < 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183-5.971, p = 0.008) as an independent prognostic factor.
CONCLUSIONS: This study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.

UNASSIGNED: Human epidermal growth factor receptor 2 (HER2) is a tumor biomarker with significant prognostic and therapeutic implications for invasive ductal breast carcinoma (IDC).
UNASSIGNED: This study aimed to explore the effectiveness of a multisequence magnetic resonance imaging (MRI)-based machine learning radiomics model in classifying the expression status of HER2, including HER2-positive, HER2-low, and HER2 completely negative (HER2-zero), among patients with IDC.
UNASSIGNED: A total of 402 female patients with IDC confirmed through surgical pathology were enrolled and subsequently divided into a training group (n = 250, center I) and a validation group (n = 152, center II). Radiomics features were extracted from the preoperative MRI. A simulated annealing algorithm was used for key feature selection. Two classification tasks were performed: task 1, the classification of HER2-positive vs. HER2-negative (HER2-low and HER2-zero), and task 2, the classification of HER2-low vs. HER2-zero. Logistic regression, random forest (RF), and support vector machine were conducted to establish radiomics models. The performance of the models was evaluated using the area under the curve (AUC) of the operating characteristics (ROC).
UNASSIGNED: In total, 4506 radiomics features were extracted from multisequence MRI. A radiomics model for prediction of expression state of HER2 was successfully developed. Among the three classification algorithms, RF achieved the highest performance in classifying HER2-positive from HER2-negative and HER2-low from HER2-zero, with AUC values of 0.777 and 0.731, respectively.
UNASSIGNED: Machine learning-based MRI radiomics may aid in the non-invasive prediction of the different expression status of HER2 in IDC.