We retrospectively analyzed consecutive patients with HER2-positive metastatic breast cancer who received T-DXd at a single Chinese cancer center between March 2023 and March 2026. Progression-free survival (PFS), overall survival (OS), systemic and intracranial response, safety, prognostic factors, and exploratory subsequent treatment strategies were assessed. Among 173 eligible patients, 80.3% had received prior HER2-directed TKIs and 41.6% had CNS metastases. After a median follow-up of 14.3 months, median PFS and OS were 14.1 and 31.1 months, respectively. The objective response rate was 54.5% among 154 patients with measurable systemic disease, while the CNS objective response rate was 46.3% among 67 patients with measurable CNS lesions. Among patients with measurable CNS lesions, the CNS-ORR was comparable between patients with and without peri-T-DXd local treatment (53.8% vs. 44.4%, p = 0.21). Greater prior treatment exposure was associated with shorter PFS, whereas HER2 IHC 3+ disease was independently associated with longer OS and showed a trend toward improved PFS compared with HER2 IHC 2+/FISH-positive disease. Interstitial lung disease occurred in 13 patients (7.5%), all grade 1–2. Among 148 patients included in the maintenance analysis, 23 switched to alternative maintenance regimens after initial benefit from T-DXd. In an exploratory analysis, no statistically significant differences in PFS or OS were observed between patients who continued T-DXd and those who switched to maintenance therapy. However, these findings require cautious interpretation because of immortal-time bias, selection bias, and limited sample size. T-DXd demonstrated clinically meaningful systemic and intracranial activity with manageable toxicity in this heavily pretreated real-world cohort.

Breast cancer (BC) persists as a major cause of deaths associated with cancer among women globally, emphasizing the urgent need for innovative therapies. Trophoblast cell surface antigen 2 (Trop-2), a transmembrane glycoprotein involved in tumor growth, proliferation, and metastasis, has emerged as a promising therapeutic target. Trop-2-targeted antibody-drug conjugates (ADCs) improve the efficacy and reduce the safety concerns while compared to traditional chemotherapy by selectively delivering cytotoxic agents to tumor cells that express Trop-2. The expression of Trop-2 is higher in many solid tumors and is associated with poor prognosis. Various Trop-2-targeted ADCs, such as sacituzumab govitecan (SG), sacituzumab tirumotecan (SKB264), and datopotamab deruxtecan (Dato-DXd), are being actively investigated for advanced triple-negative breast cancer (TNBC) and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC. This review discusses the clinical progress and outcomes of these Trop-2 ADCs, their potential utility in combination with immunotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors and the ongoing clinical trials, and their efficacy in the treatment of patients with brain metastases, shaping the future of Trop-2-directed cancer treatment. Overall, Trop-2-targeted ADCs were promising in treating HER2- BC, with the potential to improve patient outcomes, enhance the quality of life, and pave the way for future Trop-2-focused research. Especially, SG has shown substantial efficacy in treating both TNBC and HR+/HER2- BC, with a tolerable safety profile, and an encouraging efficacy over standard chemotherapy. Trop-2 ADCs have made significant progress in BC therapy; however, many challenges remain, which require further investigation.

This study aimed to investigate the clinicopathological significance of pulmonary metastasis in breast cancer patients and to evaluate the prognostic outcomes of lung metastasis subtypes. A retrospective analysis was conducted on breast cancer patients who underwent lung nodule biopsy at Peking University Cancer Hospital between 2010 and 2024. We identified 180 biopsied patients. Analyses of receptor discordance and survival were performed in the 154 pulmonary metastasis cases and primary lung cancers were described only for differential diagnosis. Among 2,857 breast cancer patients with lung nodules, 180 (6.3

3071 Background: Determining the human epidermal growth factor receptor 2 (HER2) status is essential in metastatic breast cancer (MBC) management. To establish the clinical validity of [ 18 F]AlF-HER2-BCH PET/CT (HER2-PET), we assessed the diagnostic accuracy of qualitative and quantitative HER2-PET assessment to predict HER2 expression by immunohistochemistry (IHC), including HER2-negative and -low breast cancer. Methods: This prospective multicenter trial enrolled treatment-naïve patients with newly diagnosed, non-rapidly progressive breast cancer across all molecular subtypes. Paired HER2 PET and [ 18 F]FDG PET/CT (FDG-PET) scans were acquired within a standardized 7-day. Tumor uptake was quantified using maximum standardized uptake value (SUVmax) and target-to-background ratios (TBR), and analyzed via general linear mixed models. Results: Between 2020 to June 2025, 240 patients were analyzed. Comparative analysis revealed superior diagnostic performance of whole-body HER2-PET versus FDG-PET for malignant lesion detection: sensitivity (97.6% vs 89.9%), specificity (83.9% vs 77.4%%), and overall accuracy (96.4% vs 88.9%). Quantitative HER2-PET analysis revealed significantly different SUVmax values across HER2 expression categories (median [IQR]: HER2-positive 13.1 [9.2-20.7] vs HER2-low 7.3 [5.1-8.9] vs HER2-negative 3.2 [2.7-4.5]; P<0.001), demonstrating strong correlation with IHC/FISH-defined HER2 status. In contrast, FDG-PET uptake showed no association with HER2 status (P=0.5). Among 10 discordant cases between HER2-PET and standard IHC/FISH: eight (80%) represented confirmed biological heterogeneity, with differing HER2 status across metastatic sites; two (20%) IHC 1+ cases exhibited PET-positive/FISH-amplified patterns, suggesting potential IHC false-negative results. Conclusions: [ 18 F]AlF-HER2-BCH PET/CT provides comprehensive HER2 profiling beyond single-biopsy IHC, offering new therapeutic insights for HER2-low/negative metastatic breast cancer through whole-body molecular visualization. Clinical trial information: NCT04547309 . Diagnostic performance of Al 18 F-HER2-BCH PET/CT and 18 F-FDG PET/CT, in the detection of primary and metastatic lesions in the evaluable imaging core population (N participant=240, N Biopsy-proven lesion=359). HER2 PET FDG PET Difference^ P Value* Participants True positive 207 199 -- -- True negative 26 22 -- -- False positive 2 4 -- -- False negative 5 15 -- -- Sensitivity 97.6% (94.7 to 99.1) 93.0% (88.6 to 95.9) 4.65% (0.32 to 8.98) 0.036* Specificity 92.8% (77.9 to 99.0) 84.6% (66.4 to 94.7) 8.24% (-6.8 to 23.3) 0.342 Positive predictive value 99.0% (96.6 to 99.9) 98.0% (95.2 to 99.4) 1.0 (-1.1 to 3.1) 0.398 Negative predictive value 83.9% (67.2 to 93.7) 59.5% (43.3 to 74.1) 24.4 (6.8 to 42) 0.009** Accuracy 97.1% (94.2 to 98.7) 92.1% (87.8 to 95.2) 5.0 (1.3 to 8.7) 0.008**

BACKGROUND:Bone is one of the most common sites of metastasis in advanced breast cancer. Incadronate disodium, a third-generation bisphosphonate, has demonstrated efficacy in relieving bone-related symptoms. However, there are few studies on the efficacy and safety specifically for bone metastases in advanced breast cancer. The study aims to evaluate the efficacy and safety of incadronate disodium in the treatment of bone metastases in patients with advanced breast cancer. METHODS:A retrospective real-world analysis was conducted on patients with advanced breast cancer and bone metastases who received incadronate disodium at our department from August 2021 to March 2024. Patients were assessed for bone pain relief, mobility improvement, and related adverse effects. RESULTS:A total of 181 patients were included. For all patients whose effects could be evaluated (n = 160), the overall pain relief rate was 81.6%, and the overall mobility improvement rate was 88.9%. Patients with more severe baseline pain experienced greater pain relief, while those with less severe pain had fewer mobility limitations and better improvements after treatment. The main adverse effects were fever, fatigue, elevated transaminases, myalgia, and anorexia. No cases of jaw osteonecrosis occurred. DISCUSSION:In this study, incadronate disodium showed high rates of pain relief and improved mobility, with greater benefits observed in patients with more severe baseline pain and with a favorable safety profile. Longterm safety monitoring indicated minimal impact on renal function and electrolytes, though attention is needed for potential risks like Medication-Related Osteonecrosis of the Jaw (MRONJ) and hypocalcemia. Pre-treatment dental evaluation and daily calcium/vitamin D supplementation are recommended to mitigate these risks. The study also notes that switching to incadronate after disease progression can be beneficial. However, as a single-center retrospective study without a control group, these findings require further validation through prospective randomized controlled trials. CONCLUSION:Incadronate disodium is effective and safe in relieving bone pain and improving mobility in advanced breast cancer patients with bone metastases. It represents a promising treatment option for this patient population.

Background: Cancer therapy-induced thrombocytopenia (CTIT) is a common hematologic toxicity for patients with breast cancer (BC) causing anti-cancer therapy delays, dose reductions, and discontinuation. As a novel oral thrombopoietin-receptor agonist (TPO-RA), hetrombopag might raise platelets in patients with CTIT. We carried out a prospective, single-arm trial to assess the efficacy and safety of hetrombopag monotherapy in CTIT among patients with BC (ChiCTR2200062811). Methods: Thrombocytopenic patients with BC (Age ≥18 years, platelet counts<75×109/L) caused by anti-tumor treatments were eligible. The enrolled patients received hetrombopag monotherapy (5.0mg, qd) until reaching a recovery in PLT ≥ 80×10 9 /L or an increase of ≥50×109/L compared to the baseline. The treatment would stop when patients accepted 14 consecutive days of treatment or reached the discontinuation criteria. Platelet examination was taken every 3 days during the study period. The daily blood test was required if the baseline platelet counts <50×109 /L. The primary endpoint was platelet response within 14 days, denoted by a recovery in PLT ≥75×109/L compared to the baseline. The secondary endpoints included the proportion of patients with platelets recovered to ≥ 100×10 9 /L, the proportion of patients with platelet transfusion, the incidence of dose reduction, delay, or discontinuation of consecutive cancer therapy cycles, and the safety. Results: From January 1, 2024, to June 30, 2024, 19 patients were screened for eligibility. The baseline characteristics were as follows: The median age was 51, with the majority (89.5%,17/19) at clinical stage IV. All patients with BC were treated with different anti-tumor regimens (31.6% (6/19) with chemotherapy therapy only, 21.1% (4/19) with antibody-drug conjugate (ADC) therapy, 15.8% (3/19) with chemotherapy plus targeted therapy, 15.8% (3/19) with endocrine therapy plus targeted therapy, 5.3% (1/19) with chemotherapy plus PD-1 inhibitors, 5.3% (1/19) with chemotherapy plus PD-1 inhibitor and antiangiogenic agent, 5.3% (1/19) with ADC plus antiangiogenic agent). Among them, 42.1% (8/19) of patients have received ≥3 lines of therapy. The median time from the last anti-tumor treatment to meet the inclusion requirement was 7 days (range, 1-22 days). The median value of baseline platelet counts was 65×10 9 /L (range, 28-74×10 9 /L). All patients experiencing ≥ grade 2 thrombocytopenia (PLT<75×10 9/L) after anti-tumor received hetrombopag monotherapy 5.0mg/day. Among them, 10.5% (2/19) experienced grade 3 thrombocytopenia. Treatment response was 89.5% (17/19), with a median time of 3 days (range, 3-9 days) to respond. The proportion of patients with platelets recovered to ≥100×109/L was 68.4% (13/19), with a median time of 6 days (range, 3-6 days) to respond. The incidence of dose reduction and delay of consecutive planned chemotherapy cycles were 18.8% (3/16, 3 patients had changed treatments due to disease progression or turning into maintenance therapy) and 42.1% (8/19), respectively. Especially, the platelet counts of 2 patients with severe thrombocytopenia (PLTs were 28×109/L and 39×109/L at baseline, respectively) increased to ≥100 × 109/L in 6 days after hetrombopag treatment. For safety, during the treatment of herombopag, there were 15.8% (3/19), 10.5% (2/19), and 5.3% (1/19) experienced grade 3-4 white blood cell count decreasing, neutrophil count decreasing, and anemia, respectively. No thrombosis was observed. There were no ≥ grade 3 increased AST and/or ALT. Conclusion: In this study, hetrombopag monotherapy is efficacious and well tolerated, substantiating its potential role as a novel treatment strategy for CTIT patients with breast cancer. Citation Format: Hanfang Jiang, Anjie Zhu, Huiping Li, Yaxin Liu, Ran Ran, Guohong Song, Bin Shao, Jiayang Zhang, Nan Wang. Prospective phase II study on the efficacy and safety of hetrombopag for the treatment of cancer therapy-induced thrombocytopenia in patients with breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-02-12.

BACKGROUND:Patients with breast cancer exhibit heterogeneity in the expression of the human epithelial growth factor receptor 2 (HER2). Clinically, re-biopsying recurrent or metastatic lesions presents substantial challenges. This study aimed to evaluate the efficacy of HER2-targeted PET/CT imaging in identifying HER2 expression in breast cancer lesions and monitoring therapeutic responses. PATIENTS AND METHODS:This exploratory analysis used data from a prospective study that included adult patients with breast cancer who underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT imaging at Beijing Cancer Hospital between June 2020 and July 2023 (NCT04547309). RESULTS:Fifty-nine participants, with a median age of 55 years, were analyzed. Lesions imaged with HER2-targeted PET/CT before anti-HER2 therapy exhibited higher SUVmax values than after therapy in HER2 immunohistochemistry (IHC) 3 + lesions (19.9, 95% CI: 15.7-25.3 vs 9.8, 95% CI: 5.6-14.7; P = .006). A significant positive correlation was observed between SUVmax on HER2-targeted PET/CT and IHC before therapy (P = .034), with higher SUVmax values noted in lesions with positive HER2 pathology compared to those with negative HER2 status (17.9 ± 13.2 vs 1.1 ± 0.3; P = .007). HER2 expression heterogeneity was confirmed both between primary and metastatic lesions (22.9%) and among different metastatic sites (26.7%) as assessed by HER2-targeted PET/CT. A superior therapeutic response correlated with higher pretreatment SUVmax values. The HER2-targeted PET/CT procedure was well-tolerated by all patients. CONCLUSION:HER2-targeted PET/CT imaging offers a practical, non-invasive, and quantitative approach for assessing HER2 status in breast cancer patients, facilitating the optimization and personalization of therapeutic strategies by oncologists.

12059 Background: Bone metastasis is a common site of metastasis in malignant tumors. For patients (pts) with bone metastasis, pain is the predominant symptom, significantly impairing the quality of life. SHR-2017, a first-in-class fully human monoclonal antibody targeting RANKL/NGF, is designed to prevent skeletal-related events and alleviate pain in pts with bone metastasis. Here, we present the preliminary pharmacokinetics, pharmacodynamics, efficacy and safety results from a multicenter, open-label, single-arm phase 1b study in pts with bone metastasis from breast cancer. Methods: Breast cancer pts with at least one bone metastasis and an average Numeric Rating Scale (NRS) score of ≥ 4 at the index bone metastasis cancer pain site at baseline were eligible. Pts could be undergoing stable anti-tumor treatment or have no plan to change their anti-tumor treatment within 2 weeks after drug administration in this study. Pts received subcutaneous injection of SHR-2017 at 180 mg every 4 weeks for 6 cycles. To assess pain, pts maintained a diary (daily through week 8 and then weekly to week 48) to record the average and worst pain over the previous 24 h (on a numeric rating scale from 0 = no pain to 10 = worst possible pain) at the index bone metastasis cancer pain site. Results: As of Dec 31, 2024, 22 pts were enrolled and treated (prior bone targeted agents [BTA] use, 36%; mean NRS of average pain, 4.17 [SD: 0.76]). Following a single dose, the median time to peak concentration of SHR-2017 was 7 days, with a mean half-life (t 1/2 ) of 11.4 days and a mean clearance (CL/F) of 0.88 L/day. Among 12 pts without prior BTA use, a reduction in urine N-telopeptide of type I collagen adjusted for urine creatinine (uNTX/Cr), a biomarker for bone resorption, was evident by cycle 1 and sustained over time; the median reduction from baseline was -83.0% (range -96.9% to -60.6%) at week 5 (C2D1). By week 13 (C4D1), among 8 pts without prior BTA use, the median reduction in uNTX/Cr was -78.7% (range -93.1% to -64.6%). Daily NRS score showed a continuous decrease during cycle 1 in all pts, the mean reductions from baseline in average and worst pain were -1.95 (SD: 1.21) and -1.90 (SD: 1.46) at week 2, respectively. By week 4, the reductions were -2.46 (SD: 1.03) and -2.45 (SD: 1.45), respectively. Treatment-related AEs (TRAEs) occurred in 7 (32%) pts (grade 1, n = 6; grade 2, n = 1), with the most common being increased parathyroid hormone (PTH), the one grade 2 TRAE being rash. There were no TRAEs leading to dose discontinuation. Conclusions: Preliminary data indicated promising anti-bone resorption and analgesic effects, with a favorable safety profile for SHR-2017 in pts with bone metastasis from breast cancer. The trial is ongoing to further evaluate SHR-2017 following multiple dosing. Clinical trial information: NCT06380881 .

AIMS:The study aimed to evaluate the effectiveness and safety of everolimus combined with endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer. METHODS:Data from adult patients with HR+/HER2- advanced breast cancer at Beijing Cancer Hospital between January 2012 and February 2025 were analyzed retrospectively. RESULTS:A total of 137 patients were included and the median progression-free survival (PFS) was 4.13 months (95% confidence interval [CI]: 2.86-5.40). The objective response rate and disease control rate (DCR) were 10.9% and 51.1%, respectively. No significant difference was found in PFS between different lines of therapy (p = 0.433) or different combination drugs with everolimus (p = 0.528). The median PFS in patients without prior use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was 4.20 months, compared to 3.07 months in patients previously treated with CDK4/6 inhibitors (p = 0.466). The patients with prior CDK4/6 inhibitors for more than six months exhibited an extended PFS when subsequently treated with everolimus plus endocrine therapy (7.63 vs. 2.03 months, p<0.001). Meanwhile, everolimus-based treatment was generally well-tolerated. CONCLUSION:For patients with HR+/HER2- advanced breast cancer, everolimus combined with endocrine therapy may serve as an alternative option after disease progression on CDK4/6 inhibitors.

e13104 Background: Sacituzumab govitecan (SG) is the first antibody-drug conjugate targeting trophoblast cell - surface antigen 2 (Trop-2). Clinical trials such as ASCENT and TROPiCS-02 have demonstrated that SG improves progression-free survival (PFS) and overall survival (OS) in metastatic triple-negative breast cancer (mTNBC) and HR+/HER2- breast cancer following prior therapy. While SG has been approved in China for two years, real-world data on its efficacy and safety in Chinese metastatic breast cancer (MBC) patients remain limited. This multicenter real-world study aimed to evaluate SG’s efficacy and safety in Chinese patients with HER2-negative MBC. Methods: Data were retrospectively collected from HER2-negative MBC patients treated with SG and received first radiological evaluation between June 2023 and October 2024. Outcomes included real-world progression-free survival (rwPFS), objective response rate (ORR), disease control rate (DCR), real-world overall survival (rwOS), and safety. Results: Fifty-eight patients were included, with a median age of 53.4 years. Patients had a median of three prior systemic treatments (range 1–10) for metastatic disease. The cohort included 43 TNBC patients (74.1%) and 15 HR+/HER2- patients (25.9%), with metastatic sites in the liver (55.2%), lung (41.4%), brain (22.4%), and bone (53.3%). The overall cohort showed an ORR of 36.2%, a DCR of 81.0%, and a median rwPFS of 3.9 months. For mTNBC, the ORR was 34.8%, DCR 79.1%, and median rwPFS 4.2 months. Among four mTNBC patients receiving SG combined with PD-1 inhibitors, the ORR reached 50.0%. In HR+/HER2- patients with median 2 lines of prior endocrine therapy, the ORR was 40.0%, DCR 86.7%, and median rwPFS 3.5 months. In 13 patients with brain metastases, the ORR was 30.7%, with a median rwPFS of 6.3 months. OS data remain immature; the 6-month OS rate was 76.8%. Safety analysis identified neutropenia (53.5%) and diarrhea (22.4%) as the most common adverse events (AEs), with grade ≥3 rates of 17.2% and 6.9%, respectively. Febrile neutropenia occurred in 3.5% of patients, while no ocular toxicity was observed. Granulocyte colony-stimulating factor (G-CSF) was used prophylactically in 34.5% of cases. Conclusions: This real-world study confirms the efficacy and manageable safety profile of SG in heavily pretreated Chinese patients with HER2-negative metastatic breast cancer. SG demonstrated significant disease control in both TNBC and HR+/HER2- subgroups, with consistent PFS. The observed efficacy in patients with brain metastases warrants further investigation. Lower rates of neutropenia and diarrhea compared to global trials may reflect enhanced supportive care, such as prophylactic G-CSF use. These findings provide valuable insights into the role of SG in Chinese clinical practice and highlight areas for future research to optimize outcomes.

BACKGROUND:HLX02 (Zercepac®) is the first trastuzumab biosimilar manufactured in China. This study presents the first real-world comparison of HLX02 with reference trastuzumab (RTZ) plus pertuzumab and chemotherapy as the first-line treatment for HER2-positive metastatic breast cancer (MBC) patients. METHODS:Medical data of patients with HER2-positive MBC who received HLX02 or RTZ, both combined with pertuzumab and various chemotherapies as the first-line therapy at Beijing Cancer Hospital from January 2019 to August 2023 were reviewed retrospectively. The survival outcomes, efficacy, and adverse events were analyzed. RESULTS:In total, 118 patients were included in this study retrospectively, among whom 66 patients received RTZ and 52 received HLX02. No significant difference was observed in progression-free survival (PFS) between the groups (median PFS: 22.0 months for RTZ vs. 19.0 months for HLX02, P = .832). Additionally, the objective response rate, disease control rate, and safety profiles were similar across both groups. Of all 118 patients, 20 (16.9%) patients experienced progression in the central nervous system (CNS), with a median time to CNS progression of 15.0 months (95% confidence interval, CI, 12.8-17.2). CONCLUSION:The real-world data suggested that both HLX02 and RTZ, when combined with pertuzumab and various chemotherapy regimens, offer comparable efficacy and safety as first-line treatments for HER2-positive advanced breast cancer patients in China.

Anti-angiogenesis offers an important treatment strategy for metastatic breast cancer (MBC). Metronomic chemotherapy (MCT) provides antiangiogenic effects without increased toxicities, making it good partner for antiangiogenic therapy. We conducted the present retrospective study to evaluate the efficacy and safety of anlotinib plus MCT for HER2 negative MBC. Patients with HER2 negative MBC who received metronomic chemotherapy (Vinorelbine (NVB), Capecitabine (CAPE), Etoposide (VP-16)) with anlotinib were retrospectively analyzed from Jan 2019 to Dec 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. 48 patients with HER2 negative MBC were enrolled. 19 (39.6

Recent clinical trials have suggested that solid cancers with mismatch repair (MMR) deficiency are highly responsive to immunotherapy, regardless of cancer types. Previous MMR-related studies on breast cancer have predominantly focused on germline variants. However, the somatic MMR alterations have not been comprehensively characterized in breast cancer. In this study, we integrated genomic, transcriptomic, and clinical data from over 3000 breast cancer cases across six public cohorts. Our findings revealed that 1.2% of breast cancers harbored oncogenic somatic MMR alterations, with triple-negative breast cancer (TNBC) demonstrating the highest mutation rate at 3.1%. Additionally, somatic MMR alterations were significantly associated with microsatellite instability-high (MSI-H) and MMR-related mutational signatures, indicating that somatic MMR alterations led to impaired function of the MMR system. Biallelic inactivation of MMR genes resulted in a more pronounced loss of MMR function compared to monoallelic inactivation. Importantly, these MMR alterations significantly increased the tumor mutational burden (TMB) and neoantigen load in breast cancer, regardless of MSI-H status. These findings indicate that the frequency of MMR alterations is highest in TNBC and that MMR alterations in breast cancer can lead to MMR functional deficiencies, suggesting that some patients harboring such alterations may benefit from immunotherapy.

Objective:This study aimed to evaluate the clinical utility of [68Ga]Ga-RM2 positron emission tomography/computed tomography (PET/CT), in comparison with 18F-fluorodeoxyglucose ([18F]FDG) PET/CT, for staging and prognosis in patients with estrogen receptor-positive (ER+) breast cancer. Methods:This prospective study enrolled nine female patients with breast cancer (mean age 45.5±11.5 years). Eight patients were confirmed to have ER+ disease. All participant underwent both [68Ga]Ga-RM2 PET/CT and [18F]FDG PET/CT scans within a one-week interval. The maximum standardized uptake values (SUVmax) was measured for primary tumors, lymph nodes, and metastatic lesions. The physiological distribution of [68Ga]Ga-RM2 was also evaluated. Results:No adverse events were observed. Metastatic were identified in lymph nodes (n=29 lesions), bone (n=19), liver (n=7), brain (n=3), and multiple other sites. [68Ga]Ga-RM2 demonstrated a significantly higher median SUVmax than [18F]FDG across all lesions [7.5 (interquartile range, IQR, 3.4-14.0) vs. 4.0 (IQR, 2.3-6.1); P<0.001]. Similarly, the tumor-to-background ratio (TBR) was significantly superior with [68Ga]Ga-RM2 for all type of lesions: primary tumors [12.3 (IQR, 10.4-18.3) vs. 7.0 (IQR, 6.0-10.0); P<0.001], lymph node metastases [17.8 (IQR, 4.4-39.0) vs. 4.7 (IQR, 2.7-10.2); P<0.001], hepatic metastases [5.4 (IQR, 3.7-8.3) vs. 1.0 (IQR, 0.9-1.5); P<0.001], and osseous metastases [13.9 (IQR, 7.3-18.0) vs. 4.3 (IQR, 1.6-5.9); P<0.001]. Physiological uptake of [68Ga]Ga-RM2 was the highest in the pancreas (SUVmax, 77.82±22.64), with moderate uptake in the kidneys (2.82±0.62), heart (1.83±0.29), and liver (1.33±0.41). Conclusions:[68Ga]Ga-RM2 PET/CT demonstrates superior uptake metrics for the detection of metastatic lesions, particularly in the brain and breast, suggesting its potential as a valuable complementary imaging modality to [18F]FDG PET/CT. These promising foundings warrant further validation in larger cohorts to confirm their clinical impact and to standardize imaging protocols.

The aim of this study is to examine the incidence of receptor expression and the changes in subtypes observed between the primary breast cancer lesion and liver metastasis, and to investigate the impact of treatment patterns for various liver metastasis subtypes on patients’ survival outcomes. A retrospective analysis was conducted on patients with breast cancer liver metastases at Peking University Cancer Hospital between 2008 and 2024. A total of 542 cases of breast cancer with liver metastasis were analyzed, of which 453 cases (83.6

To assess the diagnostic performance and the whole-body heterogeneity of HER2 expression on Al18F-NOTA-HER2-BCH PET/CT in patients with HER2-low breast cancer. In this prospective study conducted from November 2021 to March 2024, participants with HER2-low breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. Participants were pathologically confirmed as HER2-low (immunohistochemistry score of 1 + or 2 + without HER2 gene amplification on in situ hybridization). PET/CT images were acquired 3.5 h after injection of 200 MBq of Al18F-NOTA-HER2-BCH. The maximum standardized uptake value (SUVmax) and target-to-background ratios (TBR) were used to quantify tracer uptake. Fifty-two participants with HER2-low breast cancer (mean age, 53.0 ± 11.0; 52 females) underwent Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT with paired tumor biopsies. No adverse events occurred. The median SUVmax and TBR of 52 HER2-low biopsy lesions on Al18F-NOTA-HER2-BCH PET/CT were lower than that on 18F-FDG PET/CT (6.6 vs. 10.5, P <.001; 8.0 vs. 10.6, P =.009). A total of 269 suspicious lesions were detected, 18F-FDG PET/CT depicted more suspected HER2-low positive lesions in breast (100

Extracellular vesicle miRNAs (EV-miRNAs) are strongly linked to cancer progression, metastasis, and drug resistance, making them promising biomarkers for precision diagnosis. However, the clinical potential of EV-miRNA-based liquid biopsies is hindered by the low abundance of EV-miRNAs and the tedious detection procedure including EV separation, purification and miRNA quantification. Here, we develop a novel one-step catalytic hairpin assembly (CHA)-based fluorescent assay for sensitive detection of EV-miRNAs assisted with DNA-mediated membrane fusion (DMF) and DNA tetrahedron (DT) (DMF-DT-CHA). This DMF-DT-CHA assay facilitates the membrane fusion between liposome and EV through interactions between DNAs for DT-CHA probe delivery into EVs, and followed by DT-CHA, which recognizes target miRNAs to initiate non-enzymatic signal amplification via CHA-based fluorescence emission. We analyzed EVs from three breast cancer cell sources using DMF-DT-CHA and the results were consistent with qPCR and the platform achieved the limit of detection (LoD) of 0.24 fM for EV-miRNAs. We performed a clinical evaluation of the DMF-DT-CHA assay platform. Recipient operating characteristic curves (ROCs) showed that the DMF-DT-CHA platform was an excellent classifier for distinguishing breast cancer (BC) patients from healthy donors and breast cancer patients from benign breast nodule patients, with area under the curve (AUC) values of 0.850 and 0.835, respectively, as well as an accuracy of 81.1 % in response to treatment for triple-negative breast cancer. DMF-CT-CHA assay platform has clinical potential for cancer diagnosis and treatment monitoring.

Background: Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose: To compare an affibody-based tracer, (AlF)-F-18-NOTA-HER2-BCH, and fluorine 18 (F-18) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods: In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both (AlF)-F-18-NOTA-HER2-BCH and F-18-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUVmax) and target to background ratio (TBR) and compared using a general linear mixed model. Results: A total of 42 participants (mean age, 56.3 years +/- 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with (AlF)-F-18-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with F-18-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with (AlF)-F-18-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with F-18-FDG. (AlF)-F-18-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than F-18-FDG. The SUVmax and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on (AlF)-F-18-NOTA-HER2-BCH images than on F-18-FDG images (median SUV(max )range, 10.4-13.5 vs 3.4-6.2; P value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; P value range, <.001 to .001). No evidence of differences in the SUVmax and TBR for chest wall or lung metastases was observed between (AlF)-F-18-NOTA-HER2-BCH and F-18-FDG (P value range, .06 to .53). Conclusion: PET/CT with the affibody-based tracer (AlF)-F-18-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using F-18-FDG.

e13103 Background: Bone is the most common metastasis site in advanced metastatic breast cancer disease. Denosumab is advocated by various guidelines with high-quality of evidence for the treatment of breast cancer patients with bone metastases (BM) to delay or reduce the occurrence of skeletal related events (SRE). Data for bone lesion repair after treatment on image is still needed in real world. This retrospective study aims to evaluate the efficacy of denosumab on breast cancer with BM by MD Anderson (MDA) criteria which is specific to BM and its safety in real world. Methods: Data of patients age ≥18 years diagnosed with advanced breast cancer with BM and treated with denosumab from June 1st 2020 to Dec 31st 2022 were retrospectively analyzed. The primary endpoint was the objective response rate (ORR) for bone lesions by MDA criteria in evaluable patients. Secondary endpoints include disease control rate (DCR) for bone lesions, risk of SRE occurrence and safety in total population. Subgroup analysis investigated the impact of the time of denosumab treatment initiation post-diagnosis of BM as well as the duration of treatment with denosumab on efficacy. Comparative analysis was performed using Chi-squared test and a p value of <0.05 was considered statistically significant. Results: Atotal of 185 patients were enrolled with median age of 52.45 (SD: 12.02) years. The median follow-up time was 25.2 months. 49 out of the 130 evaluable patients achieved partial response, resulting in an ORR of 37.69% (95% CI: 0.29-0.47), and a DCR of 90% (95% CI: 0.84-0.95). 16 out of 185 (8.65%) patients developed SRE after denosumab treatment with the median time to the first occurrence of SRE not reached. The ORR and DCR for bone lesions of starting denosumab after diagnosis of BM in ≤3 months vs. >3 months were 31.54% vs. 6.15% (p<0.001) and 68.46% vs. 21.54% (p<0.001), respectively. The ORR and DCR for bone lesions of the duration of denosumab treatment <6 months vs. ≥6 months were 4.62% vs. 33.08% (p<0.001) and 37.69% vs. 76.92% (p<0.001), respectively. Renal function impairment decreased from 33 patients before treatment to 8 patients post-treatment, while hypocalcemia increased from 1.62% to 11.35%. Osteonecrosis of the jaw occurred in one patient (1/185,0.54%) post-treatment. Conclusions: Denosumab was found to be effective and safe for breast cancer patients with BM in this large retrospective study. Early initiation and longer duration of denosumab treatment may generate better clinical outcomes for bone lesions by MDA criteria.

Background: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. Methods: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. Results: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. Conclusions: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.