bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary safety and efficacy of TQB2930, a HER2-targeted bispecific antibody in patients with advanced breast cancer: Results from a phase 1b study.
Authors: Zhang Qingyuan , Wang Jingxuan , Li Liru , Zeng Xiaohua , Zhang Han , Song Ying , Tang Dabei , Niu Xingjian , Ma Wenjie , Tu Lifan , Fu Shuang , Pan Zoucheng 
Published: June 2024

1026 Background: TQB2930 is a HER2-targeted bispecific antibody, binding to two distinct HER2 epitopes, the same domain as trastuzumab (ECD4) and pertuzumab (ECD2). This study aims to evaluate the safety and efficacy of TQB2930 for patients with advanced breast cancer after failure of standard therapy. Methods: This phase 1b, dose-escalation and expansion trial included patients preferred HER2-expressing or HER2-amplified breast cancer who had received standard therapy. In the dose-escalation phase, TQB2930 was given weekly (10mg/kg, QW), biweekly (20mg/kg, Q2W), or triweekly (30mg/kg, Q3W). After the dose-escalation phase, eligible patients were enrolled and dosed biweekly or triweekly in the expansion cohort. The primary endpoints were safety, maximum tolerated or maximum administered dose, and the secondary endpoints were immunogenicity, pharmacokinetics, and tumor response per RECIST v1.1. Results: As of Dec 20, 2023, 34 patients(pts) have received TQB2930 weekly (n=3), biweekly (n=16), and triweekly (n=15). All pts were female, the median age was 59. 22 pts had HER2 expression of ICH3+ or ICH2+ with FISH+, and the others had ICH2+ with FISH- or ICH1+. The median prior lines of therapies were 3 (range: 0-8), with one pt intolerance to first-line treatment enrolled, and the median prior lines of HER2-targeted therapies were 2 (range: 0-8). No dose-limited toxicity was observed. The main treatment-related adverse events (TRAEs) were infusion reaction, occult blood of urine, leukopenia, and neutropenia. 3 pts were reported grade≥3 TRAEs, including neutropenia, anemia, and hypokalemia. Of 31 response-evaluable pts, the objective response rate (ORR) was 25.8% with 8 partial responses (PRs) were observed (including 5 confirmed PRs and 3 PRs awaiting confirmation). The disease control rate was 80.6%. Moreover, 5 pts achieved PR at 30mg/kg (ORR 41.7%), including one with prior exposure to trastuzumab, pyrotinib, tucatinib, ARX788, and the other one prior to trastuzumab, pertuzumab, lapatinib, MRG002. The median progression-free survival for all pts was 5.5 months (95%CI 3.58-NE). Additionally, Pharmacokinetic analysis showed exposure (Cmax and AUC0-t) of TQB2930 increased linearly with doses within 10~30mg/kg. After dosing, the mean peak concentration reached at 2.5-4.3 h, and the elimination half-life of TQB2930 was 109-161 h. Conclusions: TQB2930 is well tolerated and has demonstrated promising single-agent anti-tumor activity in HER2-positive breast cancer who have failed standard anti-HER2 therapies, including multiple lines of prior HER2 targeted agents. These early signs of activity support the further exploration of combination therapy of TQB2930 and the study is ongoing. Clinical trial information: NCT06202261 .
Comprehensive analysis of TROP2, PD-L1, stromal (s)TILs, and HER2 expression patterns in patients (pts) with metastatic HR+HER2- breast cancer.
Authors: Corti Chiara , Heiling Hillary , Hughes Melissa E. , Binboğa Kurt Busem , DiLullo Molly , Li Tianyu , Tayob Nabihah , Curigliano Giuseppe , Mittendorf Elizabeth A. , Lin Nancy U. , Tolaney Sara M. , Garrido-Castro Ana Christina 
Published: June 2024

1062 Background: Immune checkpoint inhibitors (ICI) have shown limited efficacy in hormone receptor positive (HR+) metastatic breast cancer (mBC) and the optimal ICI-based combination is unknown. The TROP2 antibody-drug conjugate sacituzumab govitecan (SG) demonstrated antitumor activity with a 5.5-month median PFS in endocrine refractory HR+ mBC. Given SG's potential for anticancer immunity, we sought to evaluate expression patterns of biomarkers of interest in HR+ mBC. Methods: This retrospective study included pts with HR+HER2- mBC identified at DFCI between 10/2020 and 12/2021 who received 0-1 prior lines of chemotherapy in the metastatic setting and consented to analysis of archival FFPE tissue samples. We aimed to 1) characterize expression patterns of TROP2 (SP295 H-score), PD-L1 (22C3 CPS), sTILs and HER2 (per central pathology review) in the most recent available sample; 2) assess the prognostic value of selected biomarker combinations for overall survival (OS) defined as the time from consent to either death due to any cause or last follow-up (Cox proportional hazard models; p-value <0.05 considered significant). Results: Among 142 pts included, median age at diagnosis was 46 yrs (IQR: 40–56). Baseline characteristics are shown (Table). At least one biomarker was available for 123 subjects (86.6%). TROP2 expression (n=61) was Medium/High (M-H: 101-300) in 43 pts (70.5%) and Low (L: 0-100) in 18 (29.5%). PD-L1 central assessment (n=120) revealed CPS ≥1 (PD-L1+) in 32 pts (26.7%) and <1 (PD-L1-) in 88 (73.3%); only 7 (5.8%) pts had CPS ≥10. sTILs (n=87) were ≥10% in 14 pts (16.1%) and <10% in 73 (83.9%). When analyzing TROP2 and PD-L1 (n=61), 15 pts (24.6%) were TROP2-M-H/PD-L1+, 28 (45.9%) were TROP2-M-H/PD-L1-, 5 (8.2%) were TROP2-L/PD-L1+, and 13 (21.3%) were TROP2-L/PD-L1-. When analyzing TROP2 and sTILs (n=54), 6 pts (11.1%) were TROP2-M-H/sTILs ≥10%, 32 (59.3%) were TROP2-M-H/sTILs <10%, 2 (3.7%) were TROP2-L/sTILs ≥10% and 14 (25.9%) were TROP2-L/sTILs <10%. For TROP2 and HER2 (n=46), 26 pts (56.5%) had TROP2-M-H/HER2-low tumors, 7 (15.2%) TROP2-M-H/HER2-0, 3 (6.5%) TROP2-L/HER2-low, and 10 (21.7%) TROP2-Low/HER2-0. Median OS (n=138) was 43.8 months; stratification for selected biomarker combinations will be presented although no statistical significance was found. Correlations with NGS data and HER2DX are ongoing and will be presented. Conclusions: Analyzing biomarkers of interest in pts with HR+ mBC unveiled diverse patterns, without associations with OS. Patient characteristics. [Table: see text]
Real-world treatment outcomes in patients with HR+ HER2- advanced breast cancer treated with CDK4/6 inhibitors and endocrine therapy.
Authors: Duchnowska Renata , Soter Katarzyna , Smok-Kalwat Jolanta , Grela-Wojewoda Aleksandra , Winsko-Szczęsnowicz Karolina , Pogoda Katarzyna , Kade Grzegorz , Danielewicz Iwona , Szymanowski Bartosz , Kiszka Joanna , Streb Joanna , Kalinka Ewa , Łacko Aleksandra , Żubrowska Justyna , Ziobro Marek , Czartoryska-Arlukowicz Bogumila , Jurczyk Michał , Lewandowski Tomasz , Jassem Jacek , Bieńkowski Michał 
Published: June 2024

1067 Background: The addition of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) to endocrine therapy (ET) improves progression-free (PFS) and overall survival (OS) in hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- ABC) in 1st and 2nd line setting. The international guidelines advise using 1st line CDK4/6i; however, its superiority over 2nd line use is debatable. Methods: We retrospectively analyzed clinical data of HR+/HER2- ABC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) added to either 1st or 2nd line ET. Results: A total of 1511 pts (PAL=507; RIB=724; ABM=280) from 11 cancer Polish centers treated between Sep 2017 and Dec 2023. Median follow-up was 29.6 (95%CI 28.2 to 30.9) months (m). Mean age was 62.6±11.9, 58.9±12.2 and 61.4±10.8 years in PAL, RIB and ABM, respectively. 815 patients (53.9%) had visceral and 1109 (73.4%) bone metastases. 1254 pts (83%) received 1st line CDK4/6i, in 841 (67%) combined with aromatase inhibitor (AI) and in 413 (33%) with fulvestrant (FUL). Second-line CDK4/6i was used in 257 pts (17%); 59 (23%) and 198 (67%) with AI and FUL, respectively. There was no difference in PFS, PFS2, and OS between three CDK4/6i in combination with AIs in 1st and 2nd line setting. Median PFS (95%CI) for 1st line AI with PAL, RIB, ABM were 29.0 (21.6-37.0), 32.0 (24.5-36.9), not reached (N/R) (21.9-N/R) m; PFS2: 37.0 (28.8-N/R), 33.0 (29.5-40.2), N/R (28.9-N/R); OS: 48.9 (42.9-N/R), 48.6 (41.9-N/R), N/R (36.7-N/R). Median PFS (95%CI) for 2nd line AI with PAL, RIB, ABM were 11.9 (9.49-N/R), 10.8 (8.27-N/R), 11.0 (6.43-N/R); PFS2: 22.7 (16.8-N/R), 32.3 (24.9-N/R), 31.0 (13.2-N/R); OS: 27.4 (24.4-N/R), 36.7 (30.1-N/R), 45.5 (29.0-N/R) (no statistical significance). In contrast, RIB+FUL was superior to PAL+FUL and ABM+FUL in both lines (Table). The safety profile was concordant with the reported data for ET + CDK4/6i. Conclusions: Identifying predictive factors of response is essential for the rational use of CDK4/6i and ET in HR+/HER2- ABC. [Table: see text]
Economic impact of longer treatment duration in first-line for HR+/HER2- metastatic breast cancer: A retrospective analysis.
Authors: Abbass Ibrahim M. , Ng Carmen , Dillon Allison , Cheng Anna , Du Toit Yolande , Basho Reva K 
Published: June 2024

1072 Background: Real-world treatment duration (TD) in the first line of therapy (1LOT) has demonstrated a strong correlation with progression-free survival (PFS). Increased TD for cancer patients (pts) in earlier lines has been linked to reduced healthcare costs by mitigating the need for costly therapies in subsequent lines, but the extent to which 1LOT costs vary based on the duration pts stay on treatment in 1LOT remains largely unknown. This study investigates the relationship between the TD of endocrine therapy (ET) plus CDK4/6 inhibition (CDKi) in 1LOT (serving as a proxy for PFS) and various healthcare cost measures incurred in 1LOT among newly diagnosed pts with HR+/HER2- metastatic breast cancer (mBC). Methods: Using the IQVIA PharMetrics Plus database, we identified adult women with newly diagnosed HR+/HER2- mBC whose 1LOT within 90 days of metastatic diagnosis (met dx) was ET + CDKi between 10/01/2016 - 06/30/2022. Pts with at least 6 months of follow-up post-met dx were included. The study followed pts from ET+ CDKi initiation until a switch, discontinuation, or a gap exceeding 90 days. Baseline characteristics were assessed 12 months before met dx. Healthcare costs (adjusted to 2022 USD) during the follow-up period were measured per patient per month (PPPM). TD was categorized based on percentile (p) distribution into six groups (<10p; ≥10p to <25p; ≥25p to <50p; ≥50p to <75p; ≥75p to <90p; and ≥90p). Cost measures included total, inpatient (inp), outpatient (outp), ER, and pharmacy (rx) costs. Generalized linear and two-part models examined the relationship between various cost measures and TD, adjusting for age, region, payer type, and Elixhauser comorbidity index (ECI). Results: The study included 1,536 pts receiving ET+ CDKi in 1LOT, with a median age of 59. The median ET + CDKi TD in 1LOT was 23.7 months. PPPM costs were $18,716; $1,044; $2,899; $63; and $14,711 for total, inp, outp, ER, and rx services, respectively. Models results indicate lower PPPM total, inp, outp and ER costs as TD increases (Table). PPPM costs were higher for the bottom 10th p (shortest TD group) compared to the top 10th p (longest TD group)(difference $6,411; $2,735; $3,297; and $205 higher for total, inp, outp, and ER visits respectively). PPPM rx costs did not vary with TD. Conclusions: Real-world TD of ET+ CDKi closely aligns with PFS reported in ET + CDKi trials, further demonstrating a strong correlation with PFS. Prolonging TD in 1LOT yields significant cost savings, primarily driven by reductions in inp, outp, and ER costs. The results underscore the need for ongoing optimization of pts selection for 1LOT for HR+ mBC. The study findings also suggest that the economic evaluation of investigated treatments should take into account treatment duration. [Table: see text]
Utidelone plus bevacizumab for the treatment of HER2-negative breast cancer brain metastases (U-BOMB): A multicenter, single-arm phase II study.
Authors: Yan Min , Lv Huimin , Liu Xinlan , Cuizhi Geng , Wang Shusen , Song Yuhua , Liu Zhenzhen , Niu Limin , Zhang Mengwei , Feng Yajing 
Published: June 2024

1081 Background: The primary treatment for brain metastases in patients with HER2-negative advanced breast cancer is predominantly local therapies like radiotherapy, owing to the limited efficacy of systemic therapies. Prior research has demonstrated utidelone's significant permeability across the blood-brain barrier and the preliminary effectiveness of bevacizumab for breast cancer brain metastases. Consequently, this study investigated the efficacy and safety of utidelone combined with bevacizumab in the treatment of advanced breast cancer brain metastases. Methods: This study was a single-arm, multi-center phase II clinical trial (NCT05357417). Eligible patients were aged 18 years or older with either radiotherapy-naive or progressive brain metastases post-radiotherapy, presented with asymptomatic or symptomatic brain metastases associated with HER2-negative breast cancer.Patients received intravenous bevacizumab (15 mg/kg on day 1 of each 3-week cycle) and utidelone (30 mg/m2 on days 1 to 5 of each cycle) until intolerance or disease progression. The primary endpoint was central nervous system objective response rate (CNS-ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Results: Between May 5, 2022, and October 25, 2023, a total of 46 patients were recruited, with a median age of 52.5 years (range, 33 to 69). Among them, 35 patients had untreated CNS lesions, while 11 had progressive brain metastases after local radiotherapy. The CNS-ORR was 43.5% (95% confidence interval [CI], 28.9%-58.9%). As of January 8, 2024, the median duration of follow-up was 14.6 months, and the median progression-free survival (PFS) was 7.7 months (95% CI: 5.5-10.8) as shown in Table. The 12-month overall survival (OS) rate reached 74.4% (95% CI: 60.0%-92.3%). The most common grade 1-2 adverse events (AEs) were peripheral neuropathy (87.5%), decreased neutrophil count (62.5%), anemia (47.5%), diarrhea (37.5%), and increased alanine aminotransferase (25%). No grade 3 or higher treatment-related AEs occurred. Conclusions: This study preliminarily shows promising efficacy and manageable safety of the combination of utidelone and bevacizumab in the treatment of HER2-negative metastatic breast cancer patients with brain metastases. Clinical trial information: NCT05357417 . [Table: see text]
Efficacy and genomic analysis of HER2-mutant, metastatic triple-negative breast cancer treated with neratinib alone or in combination with trastuzumab in the phase 2 SUMMIT basket trial.
Authors: Jhaveri Komal L. , Hurvitz Sara A. , Brufsky Adam , Bose Ron , de Miguel Maria J. , Evron Ella , Unni Nisha , Reid Sonya A. , Quinn David I. , Mahalingam Devalingam , Saura Cristina , García-Sáenz Jose A. , Martinez-Bueno Alejandro , Guerrero Angel , De La Fouchardiere Christelle , Wildiers Hans , Bischof Georg Friedrich , Bebchuk Judith D. , Eli Lisa DeFazio , Solit David B. 
Published: June 2024

1094 Background: Genomic analyses of the SUMMIT metastatic breast cancer (mBC) cohorts suggested that resistance to neratinib (N) occurred primarily via acquisition of additional HER2alterations [Smyth et al. Cancer Discovery 2020]; this finding was independently confirmed in the MutHER clinical trial [Ma et al. Clin Cancer Res 2022]. Addition of trastuzumab (T) to N + fulvestrant (F) in HR+, HER2-negative, HER2-mutant mBC revealed increased efficacy compared to N+F [Jhaveri et al. Ann Oncol 2023]. Here, we report final data from SUMMIT evaluating whether the addition of T to N could improve outcomes in patients (pts) with HER2-mutant, triple-negative mBC (representing up to 3% of triple-negative mBCs) and performed next-generation sequencing (NGS) of serial biopsies to evaluate mechanisms of sensitivity and resistance. Methods: Pts with HER2-mutant triple-negative mBC received N (original SUMMIT cohort) or N+T (in the subsequent cohort): oral N 240 mg/d, i.v. T 8 mg/kg initially followed by 6 mg/kg q3w. Loperamide prophylaxis was mandatory during the first two cycles. Efficacy endpoints: confirmed objective response rate and clinical benefit rate (RECIST v1.1 or modified PERCIST); duration of response; progression-free survival. Retrospective central NGS was performed by MSK-IMPACT (tissue) or MSK-ACCESS (plasma). Results: 10 and 17 pts with triple-negative mBC were enrolled in the N and the N+T cohorts, respectively. Median no. of prior systemic regimens for metastatic disease was 2.5 (range 0–6) for the N and 2 (range 0–7) for the N+T cohort. Efficacy findings are summarized (Table). Diarrhea was the most commonly reported adverse event (N 80% any grade; 20% grade 3; N+T 100% any grade; 18% grade 3; no grade 4/5 or permanent discontinuations in either cohort). Correlation of efficacy to central NGS analysis is ongoing and will be reported. Conclusions: Treatment with either N and/or N+T yielded promising clinical efficacy and has been included in recent NCCN guidelines for HER2-mutant, triple-negative mBC. Molecular mechanisms of intrinsic or acquired sensitivity/resistance per genomic analysis will be reported. Clinical trial information: NCT01953926 . [Table: see text]
Ipatasertib (IPA) combined with non-taxane chemotherapy (CT) for patients (pts) with previously treated advanced triple-negative breast cancer (aTNBC): The PATHFINDER phase IIa trial.
Authors: Lopez-Miranda Elena , Pérez García José Manuel , Gion Maria , Ribelles Nuria , Cortez Patricia , Alonso Romero Jose Luis , Martínez-García María , Gonzalez- Santiago Santiago , Bermejo Begoña , Morales Murillo Serafin , Carañana Vicente , Garrigós Laia , Fernández Melissa , Boix Olga , Alcalá-López Daniel , Cortes Javier , Llombart Antonio 
Published: June 2024

1098 Background: New therapies are urgently needed for aTNBC. The PI3K/AKT/mTOR pathway and its link to chemoresistance warrant further investigation in pre-treated TNBC patients. The pan-AKT inhibitor IPA, alone or combined, has shown promise for treating advanced solid tumors. This study assessed the toxicity and efficacy of IPA with non-taxane CT in aTNBC pts. Methods: PATHFINDER (NCT04464174) is a multicenter, open-label, non-comparative, phase IIa trial with a safety run-in phase. Taxane-pretreated aTNBC pts with 1-2 prior CT lines for advanced disease and ECOG 0-1 were eligible. Based on prior treatment and available slots, pts received 21-day cycles of IPA (oral, 400 mg/d for 14 d) either with capecitabine (CA) (oral, 2 g/m2/d for 14 d) (arm A); eribulin (E) (IV, 1.23 mg/m2 on d1 and d8) (arm B); or carboplatin plus gemcitabine (CG) (IV, AUC 5 on d1 and 1000 mg/m2 on d1 and d8, respectively) (arm C) until disease progression (PD) or unacceptable toxicity. Initially, the safety run-in phase included 3 pts/arm to determine phase IIa doses based on the toxicity observed after 2 cycles. The primary endpoint was incidence of adverse events (AEs) as per NCI-CTCAE v.5.0. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Analysis was exploratory with no hypothesis testing. Results: From September 2020 to October 2022, 54 pts were assigned to arms A (n = 22), B (n = 25), and C (n = 7). In arm C, 4 additional pts received a lower dose level of IPA (300 mg/d) in the safety run-in phase. Based on the toxicity profile, this arm did not proceed with the expansion phase. At data cutoff (10th November 2023), median follow-up was 13.8 (2.4-35.5, arm A) and 11.2 (0.2-36.9, arm B) months (mo). All pts discontinued treatment, mainly because of PD (74.1%). Discontinuations due to AEs were 4.5% and 4% in arms A and B, respectively. Incidence of treatment-related (1) any grade (G) TEAEs was 81.8% and 88% and (2) SAEs was 4.5% and 20% for arms A and B, respectively. G≥3 TEAEs occurring in ≥10% of pts are shown (Table). No treatment-related deaths were reported. Median PFS was 2.7 (95%CI, 1.5-4.1) and 3.8 (95%CI, 1.5-9.6) mo; median OS was 15.5 (95%CI, 11.8-19.2) and 11.5 (95%CI, 8.8-25.1) mo; and ORR was 9.1% and 36% for arms A and B, respectively. Conclusions: Combining IPA with CA and E presented an acceptable safety profile. However, adding IPA to CG was not tolerable. E + IPA showed promising efficacy regardless of PI3K/AKT status that merits further evaluation. Clinical trial information: NCT04464174 . [Table: see text]
Identification of HER2 ultra-low based on an artificial intelligence (AI)-powered HER2 subcellular quantification from HER2 immunohistochemistry images.
Authors: Jung Wonkyung , Lee Taebum , SHIN Sangwon , Brattoli Biagio , Mostafavi Mohammad , Park Gahee , Kim Sukjun , Lee Hyunwoo , Cho Yoon Ah , Cho Eun Yoon , Kim So-Woon , Pereira Sergio , Ahn Chang Ho , Ali Siraj Mahamed , Mirsky Douglas E , Ock Chan-Young 
Published: June 2024

1115 Background: HER2-targeted antibody-drug conjugates (ADCs) can effectively target tumor cells even in HER2-low breast cancers (1+ and 2+/no amp). We developed an AI-based whole-slide image (WSI) analyzer for immunohistochemistry (IHC)-stained slides, exploring a cutoff differentiating between true HER2 negative versus HER2 ultra-low. Methods: An AI-based IHC WSI analyzer was developed using 6,188 WSIs stained by 19 types of IHC including HER2 and from various cancers, annotated by 153 pathologists. The model predicts cells as tumor cells or non-tumor cells and generates HER2 expression continuous score (HER2ecs, 0-100%), quantifying IHC staining intensity of membrane, nucleus, cytoplasm, and membrane+cytoplasm separately for each cell. A total of 401 HER2 IHC WSIs were acquired from Samsung Medical Center (n=275), Kyung Hee University Hospital (n=78), and Commercial Biobank (n=48), scored as 0 (n=347) and 1+ (n=54) by pathologists. Results: In total, 67,169,114 tumor cells and 119,113,886 non-tumor cells from 401 WSIs were successfully evaluated. Comparing HER2 score 0 versus 1+ by pathologists, mean HER2ecs of nucleus (1.7% vs 4.1%), cytoplasm (6.5% vs 12.9%), and membrane (3.6% vs 8.2%) were comparable. In HER2 score 0 WSIs, membrane HER2ecs of tumor cell was 3.6 ± 7.8% (mean ± standard deviation), while that of non-tumor cell was 0.9 ± 2.9% (p <0.001 vs. tumor cell), suggesting, even in HER2 score 0 cases, tumor cell exhibits HER2 expression beyond non-specific HER2 staining intensity. Based on our internal validation dataset, membrane-specific HER2ecs of 6.0% was the optimal threshold discriminating HER2 no-staining cells versus HER2 incomplete and faint/barely perceptible cells (AI-HER2-weak) per ASCO/CAP guideline. Among HER2 score 0 by pathologists, when applying this cutoff, the proportion of WSIs showing AI-HER2-weak or higher membrane-specific HER2ecs in over 10% of all tumor cells was 23.6% (82/347). Interestingly, that of WSIs among HER2 score 1+ by pathologists was 51.9% (28/54), which is comparable to 52.3%, objective response rate of trastuzumab deruxtecan in HER2-low patients in DESTINY-Breast04. Conclusions: AI-powered subcellular-level analysis enables identification of 23.6% HER2 ultra-low WSIs among HER2 score 0 by pathologist, which is defined by AI-HER2-weak or higher membrane-specific HER2 expression ≥ 10%. Clinical validation of the AI-powered HER2 ultra-low definition is warranted.