Background:2025 European guidelines recommended transition from cytology to HPV-based cervical cancer screening. We compared both strategies in a pilot in Poland. Methods:Eligible, consenting women aged 30-59 years underwent centralized 1:1 randomization to HPV-testing or cytology (HPV or cytology arm, respectively) in 30-39, 40-49, and 50-59 years age strata in 27 clinics. Arm assignment was unblinded. HPV positive samples underwent liquid-based cytology (LBC) triage. If normal, another LBC was performed in six months. Abnormal LBC triggered colposcopy. If both LBCs were normal, p16/Ki-67 immunocytochemistry and FAM19A4/miR124-2 methylation tests were performed. Either positive triggered referral to colposcopy. In the cytology arm, abnormal results triggered another cytology after six months or colposcopy, according to routine protocols. Cervical intraepithelial neoplasia grade 2 or worse (CIN2+) detection rate in the population intended to treat was the main outcome. NCT04111835-Clinicaltrials.gov. Findings:Between 28 October 2019 and 31 December 2022, 16,795 and 16,707 women underwent primary HPV or cytological testing, respectively. 702/16,795 (4.2%; 95% CI: 3.9%-4.5%) and 499/16,707 women (3.0%; 95% CI: 2.7%-3.3%), were referred for colposcopy in the HPV and cytology arm, respectively (RR = 1.40; 95% CI: 1.25-1.57). CIN2+ was detected in 137 women (0.82%; 95% CI: 0.69-0.96%) and in 71 women (0.42%; 95% CI: 0.34-0.54%; OR = 1.93; 95% CI: 1.34-2.77), while CIN grade 3 or worse (CIN3+) was detected in 69 women (0.41%; 95% CI: 0.32%-0.52%) and in 35 women (0.21%; 95% CI: 0.15%-0.29%; OR = 1.99; 95% CI: 1.16-3.42) in the HPV and cytology arm, respectively. In HPV positive women with two normal LBCs immunocytochemistry and methylation detected 4/9 (44.4%) and 7/9 (77.8%) CIN2+ cases, respectively. Interpretation:HPV-based screening may almost double CIN2+ detection compared to cytology. It however yields more positive screening results and colposcopies. Smooth transition from cytology to HPV-based screening requires proper triage strategies and additional colposcopy services. Methylation seems to detect more CIN2+ than immunocytochemistry in HPV positive women with two normal LBCs. Funding:Polish Ministry of Health.

INTRODUCTION:Among all RET proto-oncogene variants, Y791F has been the most controversial and widely debated with regard to itspathogenicity and clinical significance. MATERIAL AND METHODS:Medical records of 104 RET Y791F variant carriers were retrospectively analyzed. The population comprised 30 probands with medullary thyroid carcinoma (MTC), 6 probands with pheochromocytoma, 63 family members, and 5 patients in whomthe RET Y791F variant was found during genetic screening. The characteristics of the 30 RET Y791F carriers with MTC were comparedwith those of the control group of 208 patients with sporadic MTC. RESULTS:The median age at surgery in the 30 probands with MTC was 58 years (range: 20-79), and in the control group with sporadic MTC it was 55 years (range: 21-80), with no statistically significant difference (p = 0.16). Multifocal MTC was observed in 8 of 30 operatedprobands (26%) and in 29 of 208 patients (13.9%) with sporadic disease (p = 0.07). Prophylactic surgery was performed in 21 familymembers. No MTC was identified in the postoperative material. Among patients under surveillance, none of the RET Y791F carriersshowed any abnormalities on thyroid ultrasound or any increase in calcitonin concentration. None of the followed-up patients (except 6after adrenalectomy) was diagnosed with pheochromocytoma. None of the 104 RET Y791F carriers had hypercalcemia. CONCLUSIONS:Based on our results, individuals with the RET Y791F variant do not require enhanced clinical surveillance or prophylactic intervention and should be managed according to general population guidelines, unless additional clinical indications arise.

Introduction:We aimed to investigate the prognostic significance of estrogen receptor status (ER)-low status in breast cancer (BC). Additionally, we compared the ER-low subgroup with ER-negative and ER-high BC according to clinical, histopathological and molecular factors. Material and methods:The analysis included medical records of BC patients treated at the National Institute of Oncology in Gliwice, Poland, between 2002 and 2018. Results:Of the 657 tumours, 14% were classified as ER-low, 52% as ER-high and 34% as ER-negative. Patients with ER-low tumours were more likely to present with T3-T4 disease compared with those with ER-high (19% vs. 12%, p = 0.089) and less frequently than ER-negative (19% vs. 29%, p = 0.092). Patients with ER-low tumours were less likely to be progesterone receptor status (PgR) negative (19% vs. 92%, p < 0.001) and G3 (22% vs. 49%, p < 0.001) compared with ER-negative. BRCA P/LP (pathogenic/likely pathogenic) variants were less frequent in ER-low than in ER-negative tumours (5% vs. 20%, p = 0.001). Overall survival (OS) was similar in both ER-high and ER-low groups (p = 0.333; 5-year OS: 93% vs. 92%, 7-year OS: 86% vs. 83%). Overall survival was non-significantly better for those with ER-low compared with ER-negative (p = 0.107). Conclusions:Estrogen receptor-low status appears to be associated with a higher T stage and PgR negativity compared with ER-high tumours, and with a lower grade and fewer BRCA P/LP variants compared with ER-negative tumours. A trend toward improved OS was observed in ER-low compared with ER-negative patients.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard of care in advanced breast cancer. While Ki67 is prognostic in early-stage disease, including adjuvant CDK4/6i, its role in metastatic setting is unclear. This study assessed Ki67’s prognostic value in advanced breast cancer treated with CDK4/6i. We conducted a retrospective analysis of patients with advanced breast cancer receiving CDK4/6i at our cancer center between 2018 and 2023. The study included 368 patients with Ki67 results. The median age was 63 years (IQR 52–70.5). 283 patients (76.9

BACKGROUND:To enhance sodium-iodide symporter expression and, thereby, radiopharmaceutical uptake/retention in differentiated thyroid carcinoma (DTC) metastases, radioiodine therapy (RAIT) can be stimulated by recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW). We investigated the association of thyrotropin (TSH) stimulation methodology with treatment outcomes in patients with radioiodine-avid distantly metastatic DTC. METHODS:Single-center retrospective cohort study involving 189 consecutive eligible patients initiating RAIT from 2005 to 2015, a period allowing sufficient follow-up to adequately assess long-term outcomes. Patients were dichotomized into "rhTSH only" or "mixed stimulation" subgroups (respectively, all RAIT activities prepared by rhTSH or ≥1 activity prepared using THW; n = 81, n = 108). Patients given only THW (n = 5) were excluded due to low numbers for statistical analysis. Endpoints comprised radiological/biochemical response and time-to-progression (TTP) and overall survival (OS) estimated via the Kaplan-Meier method. Unadjusted inter-subgroup differences underwent log-rank testing; multivariable Cox modeling assessed independent associations with TTP and OS of disease/treatment characteristics, including stimulation methodology. Propensity score matching was performed to reduce baseline differences between the stimulation groups. RESULTS:Median (minimum-maximum) follow-up was 123 (3-182) months. The best radiologic response consisted predominantly of stable disease (49%), with complete and partial responses observed in 23% and 18% of patients, respectively, and progressive disease in 10%, without significant differences between the TSH stimulation subgroups. Unadjusted analyses favored the mixed subgroup regarding TTP (141 vs. 42 months; p < 0.05) and OS (116 vs. 68 months; p < 0.01). However, after adjustment, TSH stimulation method was not independently associated with these outcomes; metastatic burden (macrometastasis) and age at DTC diagnosis were the strongest independent predictors. Consistent results were observed in the propensity score-matched cohort, with no significant differences in TTP or OS between stimulation groups. CONCLUSIONS:In radioiodine-avid metastatic DTC, rhTSH or mixed rhTSH/THW preparation is associated with comparable adjusted outcomes. Prognosis appears to be chiefly driven by metastatic burden and age. CLINICAL IMPLICATIONS:In patients with radioiodine-avid metastatic DTC, the choice between rhTSH and THW should be individualized based on comorbidities, logistics, and patient preference rather than an assumed difference in oncologic efficacy.

Purpose To evaluate the diagnostic accuracy of three proton magnetic resonance spectroscopy (1H-MRS) strategies-short echo (TE 30 ms), intermediate echo (TE 97 ms), and MEGA-PRESS-for detecting the oncometabolite 2-hydroxyglutarate (2HG) to non-invasively determine isocitrate dehydrogenase (IDH) mutation status in adult-type diffuse gliomas. Methods A cohort of 152 patients with adult-type diffuse gliomas (84 IDH-mutant, 68 IDH-wild-type) underwent preoperative 3T MRI incorporating standard morphological sequences and 1H-MRS acquisitions. Spectra were evaluated to assess the presence of a 2HG peak. Diagnostic performance was analysed independently for each method and collectively for a subgroup of patients receiving all three sequences. Results The intermediate echo (TE 97 ms) method demonstrated 100% specificity and 51.2% sensitivity, while the short echo (TE 30 ms) sequence achieved 97% specificity and 88.9% sensitivity. The MEGA-PRESS method yielded 86.7% specificity and 72.2% sensitivity but was limited by a high non-diagnostic rate (17.5%) due to artifact susceptibility. When combined, the spectroscopy methods achieved 100% sensitivity, 85.7% specificity, and 93.7% overall accuracy in detecting 2HG. Conclusion Conventional PRESS sequences (TE 30 ms and TE 97 ms) outperform MEGA-PRESS for the routine clinical detection of 2HG due to higher technical reliability. An optimized conventional PRESS protocol offers a robust, highly accurate, and non-invasive preoperative tool for identifying glioma genotypes and predicting tumour phenotypes.

INTRODUCTION:Despite extensive research, no independent molecular markers have been identified that could optimize the treatment of patients with papillary thyroid carcinoma (PTC). Proper recurrence risk stratification is crucial for further clinical management and determining the extent of treatment aggressiveness. OBJECTIVES:We focused on the TERT promoter (TERTp) variants, identified in previous research as a poor prognostic factor in patients with PTC, with the aim to analyze the clinical utility of TERTp variants in risk‑stratification of PTC patients. PATIENTS AND METHODS:We analyzed a set of 188 PTCs for BRAF V600E and TERTp variants to investigate the associations of TERTp variants with clinical factors and their impact on time‑to‑progression. RESULTS:Key observations included an association between the co‑occurrence of BRAF V600E and TERTp variants and persistent disease, poorer response to treatment, and recurrences, as compared with PTCs without these alterations. The results also suggest that the presence of TERTp variants is associated with a shorter time‑to‑relapse. CONCLUSIONS:Detection of TERTp variants should be considered in routine diagnostic procedures, as this would significantly improve patient classification into risk groups.

Trastuzumab, pertuzumab, and a taxane (THP) has been the standard first-line therapy for HER2+ advanced breast cancer for over a decade. With new regimens emerging, genomic tools like HER2DX may help identify patients who benefit durably from THP versus those requiring intensification. Here, baseline tumor tissue from 122 patients with HER2+ treated with THP in Poland was tested with HER2DX. A previously published Spanish real-world cohort (n = 93) was added to generate a combined cohort (n = 215). Univariable analyses were performed in the Polish cohort, and multivariable Cox and logistic regression models were applied to the combined cohort. A HER2DX metastatic prognostic score was trained on overall survival (OS) in the Spanish cohort and validated in the Polish cohort. In the Polish cohort, high ERBB2 mRNA scores were associated with significantly longer real-world progression-free survival (rwPFS) (33.8 vs. 17.9 months; hazard ratio [HR] 0.57; p = 0.022) and real-world overall survival (rwOS) (75.1 vs. 40.2; HR 0.48; p = 0.009). In the combined cohort, ERBB2 high-score tumors showed prolonged rwPFS (33.8 vs. 12.5; HR 0.50; p < 0.001) and rwOS (not reached vs. 37.1; HR 0.36; p < 0.001), and higher rwORR (84.4% vs. 52.0%; p < 0.001). Prognostic value was independent of clinical variables, including number of metastatic sites. Subgroup analyses showed particularly favorable outcomes in patients with <3 sites (median rwPFS 51.7 vs. 20.3 months). The HER2DX metastatic prognostic score outperformed ERBB2 alone in the validation cohort. In conclusion, the HER2DX ERBB2 mRNA score provides independent prognostic information in HER2+ advanced breast cancer treated with THP. The HER2DX metastatic prognostic score further improves prognostic accuracy.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard first-line treatment for metastatic estrogen receptor-positive, HER2-negative breast cancer, yet acquired resistance remains a major challenge. Reliable biomarkers for prognostic stratification are therefore needed. We retrospectively analyzed 174 patients treated with first-line CDK4/6i between 2018 and 2023 who underwent baseline 18F-fluorodeoxyglucose positron emission tomography. Associations between baseline SUVmax and clinical outcomes were assessed using Kaplan-Meier estimates, Cox proportional hazards models, logistic regression for early progression, and receiver-operating characteristic (ROC) analysis for cut-off determination. Higher SUVmax was significantly associated with shorter progression-free survival (PFS; HR 1.11, 95% CI 1.05-1.16, p < 0.001) and overall survival (OS; HR 1.10, 95% CI 1.02-1.18, p = 0.016). Patients with SUVmax <8.0 experienced markedly longer PFS and improved 2-year PFS compared with those with SUVmax ≥8.0. Similarly, 2-year OS was substantially higher among patients with lower SUVmax values. In multivariable analysis, SUVmax remained an independent prognostic factor for PFS. Higher SUVmax was also associated with early progression, with an 18% increase in odds per unit (OR 1.18, 95% CI 1.05-1.33). These findings demonstrate that baseline SUVmax is a strong and readily accessible prognostic biomarker in patients receiving CDK4/6i, helping to identify individuals at elevated risk of early disease progression. Prospective validation is warranted.

Sinonasal carcinoma (SNC) is the most common malignant tumor of the nasal cavity and paranasal sinuses. SNC includes the following pathological subtypes: sinonasal squamous cell carcinoma (snSCC), sinonasal adenocarcinoma (snAC), sinonasal adenoid cystic carcinoma (snACC), olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (snNEC), nuclear protein in testis carcinoma (NUT), and sinonasal undifferentiated carcinoma (snUC). Due to its rarity and diversity, SNC is poorly understood, and its management is not supported by randomized clinical trials, but rather by case series, single-center reports, or meta-analyses. The aim of this study is to comprehensively present the epidemiology and etiology, along with the clinical course of the disease, as well as methods and outcomes of treatment in patients with SNC. It was believed that this elaboration may support the daily clinical practice of those who care for patients with SNC.

Trastuzumab, pertuzumab, and docetaxel (THP) have represented the standard first-line treatment for HER2-positive metastatic breast cancer (MBC) for over a decade, following the pivotal CLEOPATRA trial. However, interim results from the DESTINY-Breast09 trial suggest that trastuzumab deruxtecan (T-DXd) may soon replace THP as the new first-line standard. Recent developments in treatment have raised new questions about how best to match therapy intensity with individual patient profiles. FDG PET/CT, routinely used for metabolic imaging, might help by identifying patients with differing prognoses based on baseline tumor activity. We investigated the prognostic relevance of baseline FDG PET/CT and its association with treatment outcomes in HER2-positive MBC patients receiving first-line THP. We retrospectively analyzed 194 patients with HER2-positive MBC who underwent baseline FDG PET/CT within 12 months before initiating THP therapy (2017–2024). SUVmax was recorded, and optimal cut-off values for progression-free survival (PFS) was determined by ROC analysis. Cox regression and logistic regression were used to identify independent predictors of PFS, OS, and long-term response (PFS ≥ 35 months). Median PFS was 29.1 months; 2-year PFS was 60.3

e13012 Background: Pertuzumab, trastuzumab, and docetaxel (TPH) remain the gold standard for first-line therapy in patients with HER2-positive advanced breast cancer (ABC). However, the therapeutic landscape is evolving rapidly, underscoring the need for predictive markers that can identify patients likely to achieve durable responses on TPH. Fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) is useful for staging in early breast cancer, but its prognostic value in the advanced disease requires further exploration. We aimed to determine whether baseline FDG-PET/CT predicts progression-free survival (PFS) in HER2-positive ABC treated with TPH. Methods: We retrospectively analyzed 195 patients with HER2-positive ABC who received TPH and underwent baseline FDG-PET/CT at our center between 2017 and 2023. The median age was 58 years (range 30–84), and all patients were female. The highest maximum standardized uptake value (SUVmax), obtained from the most FDG-avid lesion—whether the primary breast tumor, a regional lymph node, or a distant metastasis—was the key PET parameter. PFS was estimated by the Kaplan–Meier method with 95% confidence intervals (CIs) and compared using log-rank tests. The optimal SUVmax cut-off was determined by receiver operating characteristic (ROC) analysis using the Youden index. Cox proportional hazards models were applied to assess the effect of baseline SUVmax on PFS, adjusting for oligometastatic vs. polymetastatic disease, de novo vs. recurrent disease, and visceral vs. bone-only metastases. Statistical significance was set at p ≤ 0.05. All analyses were conducted using Stata version 18 (StataCorp, College Station, TX, USA). Results: The median PFS for the entire cohort was 32.3 months, with a 2-year PFS of 60.2% (95% CI 52.7–66.9). Baseline SUVmax as a continuous variable was significantly associated with PFS (HR 1.06; 95% CI 1.01–1.10; p = 0.011). The optimal SUVmax threshold was 9.7 (sensitivity 0.78; specificity 0.56; AUC 0.67). Patients with SUVmax ≤9.7 had a median PFS of 50.3 months, whereas those with SUVmax > 9.7 experienced a median PFS of 21.1 months (p < 0.001). Two-year PFS rates were 78.8% (95% CI 67.8–86.5) vs. 46.9% (95% CI 37.1–56.1) in the ≤9.7 vs. > 9.7 subgroups, respectively. The prognostic impact of SUVmax remained significant after adjusting for oligometastatic status, disease setting, and metastatic site. Conclusions: Baseline FDG-PET/CT appears to be a valuable biomarker for stratifying HER2-positive ABC patients treated with TPH into those likely to achieve long-term benefit versus those at higher risk of early progression. Prospective studies are warranted to validate these findings and refine patient selection for TPH in an era of rapidly evolving therapeutic options.

T cell-mediated rejection (TCMR) remains a challenge in kidney transplantation. Based on a histopathological biopsy examination, patients can be classified into groups such as no rejection (NR), borderline rejection (BR; Banff category 3), and acute rejection (AR; Banff category 4). Yet, this classification is not sufficient, since for the borderline cases a number of patients may require a clinical intervention. Thus, a robust classification by biopsy proteome profiling may provide a solution. In this work, kidney tissue from patients classified into NR, BR, and AR were subjected to MS-based proteomic profiling. Subsequently, a panel of four proteins (GNB4, PDK1, AGXT, CD73) was selected for validation by immunohistochemistry (IHC). This retrospective study was approved by the Bioethics Committee of the Medical University of Gdańsk, no. NKBBN/201/2021. Proteomic analysis identified 2547 proteins whose abundance profiles demonstrated strong concordance between the BR and AR groups. In a quantitative comparison between the BR and AR groups, GNB4 and AGXT emerged as significantly differentiating. Moreover, AGXT was indicated as a potential biomarker following ROC analysis. PDK1 and CD73 were found to best classify the samples in a binary analysis. IHC confirmed only upregulation of GNB4 in immune cells and PDK1 in macrophages, with no significant changes in the tubular epithelium. Thus, GNB4 and PDK1 in immune cells and macrophages have been identified as a potential target for further extensive studies. If their relevance were to be confirmed in a larger patient cohort, their IHC analysis could serve as an extension of established histopathological classification in the context of kidney transplant rejection.

Tumor cellularity (TC) in lung adenocarcinoma slides submitted for molecular testing is important in identifying actionable mutations, but lack of best practice guidelines results in high interobserver variability in TC assessments. An artificial intelligence (AI)-based pipeline developed to assess TC in hematoxylin and eosin (H&E) whole slide images (WSIs) and in tumor areas (TAs) within WSIs includes a new model (CaBeSt-Net) trained to mask cancer cells, benign epithelial cells, stroma in H&E WSIs using immunohistochemistry-restained slides, and a model to detect all cell nuclei. High masking accuracy (>91%) by CaBeSt-Net computed using 1024 H&E regions of interest and intraclass correlation coefficient >0.97 assessing TC assessments reliability by one pathologist and AI in 20 test regions of interest supported the pipeline's applicability to TC assessment in 50 study H&E WSIs. Using the pipeline, TCs assessed in TAs and WSIs were compared with those by three pathologists. Reliabilities of these ratings by the pathologists supported by the pipeline were good (intraclass correlation coefficient >0.82, P < 0.0001). The consistency of sample categorizations as inadequate or adequate (TC ≤ 20% cut point) for molecular testing among the pathologists assessing TCs without AI support was moderate in TAs (κ = 0.410, P < 0.0001) and slight in WSIs (κ = 0.132, nonsignificant). With AI support, the consistency was substantial in both WSIs (κ = 0.602, P < 0.0001) and TAs (κ = 0.704, P < 0.0001). By visualizing cancer and measuring TC in the sample, this novel AI-based pipeline assists pathologists in selecting samples for molecular testing.

BACKGROUND:Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy. The aim of this study was to investigate the use of 89Zr-DFO-Atezolizumab to image the spatio-temporal distribution of PD-L1 in preclinical mouse models and in patients with newly diagnosed GBM treated with/without neoadjuvant Pembrolizumab. METHODS:The immunoreactivity, binding affinity, and specificity of 89Zr-DFO-Atezolizumab were confirmed in vitro. Mice-bearing orthotopic GBM tumors or patients with newly diagnosed GBM treated with/without Pembrolizumab were intravenously injected with 89Zr-DFO-Atezolizumab, and PET/CT images were acquired 24, 48, and 72 hours in mice and at 48 and 72 post-injection in patients. Radioconjugate uptake was quantified in the tumor and healthy tissues. Ex vivo immunohistochemistry (IHC) and immunophenotyping were performed on mouse tumor samples or resected human tumors. RESULTS:89Zr-DFO-Atezolizumab was prepared with high radiochemical purity (RCP > 99%). In vitro cell-associated radioactivity of 89Zr-DFO-Atezolizumab corroborated cell line PD-L1 expression. PD-L1 in mouse GBM tumors was detected with high specificity using 89Zr-DFO-Atezolizumab and radioconjugate uptake correlated with IHC. Patients experienced no 89Zr-DFO-Atezolizumab-related side effects. High 89Zr-DFO-Atezolizumab uptake was observed in patient tumors at 48 hours post-injection, however, the uptake varied between patients treated with/without Pembrolizumab. CONCLUSIONS:89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.

Sinonasal carcinoma (SNC) is the most common malignant tumor of the nasal cavity and paranasal sinuses. Sinonasalcarcinoma includes seven main histopatological subtypes and three most common have been presented in Part 1of this manuscript. In the following, Part 2 of the manuscript the remaining four even more rare subtypes like olfactoryneuroblastoma (ONB), sinonasal neuroendocrine carcinoma (snNEC), nuclear protein in testis carcinoma (NUT)and sinonasal undifferentiated carcinoma (snUC) are presented and discussed as to the epidemiology, etiology, clinicalcourse, methods of treatment and outcome. It should be emphasized however that patients suspected of having a rarecancer should be directed to oncology centers with proven expertise in managing these uncommon malignancies.

Introduction: This study aimed to assess the prognostic importance of HER2-low status in breast cancer (BC). Additionally, we compared the HER2-low subgroup (defined as HER2-low1+; HER2-low2+/ISH(-)) with HER2-zero and HER2-positive subgroups according to clinical, histopathological, and molecular characteristics. Material and methods: The study analyzed the medical records of BC patients treated at the National Institute of Oncology in Gliwice, Poland, between 2002 and 2018. HER2 overexpression was assessed in postoperative specimens or samples obtained via core needle biopsy. Results: Of the 657 tumors, 176 (27%) tumors were classified as HER2-low BC, 248 (38%) as HER2-zero and 233 (35%) as HER2-positive tumors. BC patients with HER2-low tumors were more likely to have hormone receptor-positive (HR+) status compared to those with HER2-zero tumors (82.4% vs. 62.1%, p < 0.001). Specifically, patients with HER2-low1+ tumors had a higher frequency of HR+ status versus both HER2-zero and HER2-posi-tive tumors. Similarly, patients with HER2-low2+/ISH(-) tumors were more frequently characterized as HR+ compared to HER2-zero and HER2-positive patients. In the subgroup of patients with estrogen receptor negative tumors, overall survival (OS) was slightly worse than for those with HER2-low status compared to HER2-zero patients (5-year OS 72.6% vs. 86.7%, p = 0.074). Non-significantly poorer OS was noted in HER2-low1+ patients with negative prognostic factors, including HR-, progesterone receptor-negative, grade 3, and larger tumors. Conclusions: HER2-low status was associated with worse OS in breast cancer patients with certain negative prognostic factors compared with HER2-zero status. Additionally, HER2-low1+ and HER2-low2+/ISH(-) subgroups predominantly exhibited HR+ status.