Purpose: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. Patients and methods: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. Results: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824–0.982), P = 0.018]. Conclusion: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Purpose: Meaningful comparison of mutational landscapes across ethnic groups requires the use of standardized platform technology. We have used a harmonized NGS-based liquid biopsy assay to explore the differential genomic landscape of patients with initially hormone receptor-positive (HR+), HER2-negative MBC of first line metastasis or primary Stage IV at diagnosis from the United States (US) and China (CN). Methods: Plasma circulating tumor DNA (ctDNA) from 27 US patients and 65 CN patients was sequenced using the harmonized CLIA-certified, 152-gene PredicineCare™ liquid biopsy assay. Kaplan–Meier survival analysis was performed to analyze the correlation between genomic alterations and progression-free survival (PFS), and p-values were calculated using the log-rank test. Results: All patients in the CN cohort received chemotherapy and/or hormonal therapy, while 85.2% (23/27) patients in the US cohort received hormonal therapy plus CDK4/6 inhibitors. Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The prevalence of AKT1 (P = 0.008) and CDH1 (P = 0.021) alterations were both higher in the US vs. CN cohort. In addition, FGFR1 amplification were more frequent in the CN vs. US cohort (P = 0.048). PTEN deletions (P = 0.03) and ESR1 alterations (P = 0.02) were associated with shorter PFS in the CN cohort, neither of these associations were observed in the US cohort. Interestingly, a reduced association between PTEN deletion and PFS was observed in patients receiving CDK4/6 inhibitor treatment. Conclusion: The differential prevalence of ctDNA-based alterations such as FGFR1, AKT1, and CDH1 was observed in initially HR+/HER2− MBC patients in the US vs. CN. In addition, the association of PTEN deletions with shorter PFS was found in the CN but not the US cohort. The differential genomic landscapes across the two ethnic groups may reflect biologic differences and clinical implications.

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.

Background: Trastuzumab deruxtecan (T-DXd) has redefined the treatment of HER2-positive advanced breast cancer (HER2+ ABC), yet responses remain heterogeneous and accessible biomarkers are lacking. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive, routinely available systemic inflammatory marker with established prognostic value in HER2-positive disease treated with anti-HER2 monoclonal antibodies; its prognostic significance in patients receiving the antibody–drug conjugate T-DXd remains undetermined. Methods: This two-centre real-world study screened 146 consecutive patients with HER2+ ABC who received at least one cycle of T-DXd between January 2023 and June 2025 (data cutoff 16 October 2025) and enrolled 92 who met all eligibility criteria. The prespecified eligibility rule requiring a baseline complete blood count within 7 days before the first T-DXd dose was applied uniformly to every screened candidate; 34 candidates failed this rule (count drawn after the first dose, n = 16; drawn more than 7 days before, n = 17; collection date not recorded, n = 1) and one candidate was excluded because a baseline lymphocyte count at the assay lower limit rendered the derived ratio unreliable. The primary analysis evaluated baseline NLR as a continuous variable in Cox proportional-hazards regression for progression-free survival (PFS). Prespecified secondary analyses comprised median-split Kaplan–Meier analysis, quartile analysis with trend testing, individual blood components, and multivariable models. Prespecified sensitivity analyses, proportional-hazards testing, restricted cubic spline assessment of linearity, nested-model likelihood-ratio testing of the incremental value of NLR over the absolute lymphocyte count, and a centre-stratified analysis were performed. Exploratory subgroup analyses included interaction testing with false-discovery-rate correction. Results: Of 146 screened patients, 92 were enrolled (54 excluded); 39 PFS events occurred. Median follow-up by reverse Kaplan–Meier was 7.6 months; overall median PFS was 9.82 months, with 6- and 12-month PFS rates of 73.7% (95% CI 62.3–82.1) and 37.1% (22.6–51.6). Each one-unit increase in baseline NLR was associated with a 37% higher hazard of progression or death (HR 1.37, 95% CI 1.12–1.69, p = 0.0028; C-index 0.672). At the cohort median cut-off (2.157), high NLR conferred shorter PFS than low NLR (median 7.66 vs. 11.50 months; HR 2.30, 95% CI 1.21–4.38; log-rank p = 0.0096). Quartile analysis showed a significant dose–response trend (HR per quartile 1.58, 95% CI 1.16–2.13, p for trend = 0.0033), with Q4 versus Q1 HR 4.14 (1.52–11.26, p = 0.0053). Among individual components, only the lymphocyte count showed a significant median-split association (log-rank p = 0.011), and NLR provided prognostic information beyond the lymphocyte count (likelihood-ratio p = 0.039) and beyond a clinically driven multivariable model (likelihood-ratio p = 0.014; ΔC-index +0.077). In the clinically driven multivariable model (n = 92, 7.8 events per variable), NLR remained an independent prognostic factor (HR 1.36, 95% CI 1.09–1.70, p = 0.0062), and estimates were consistent across a minimal model, two extended models and a ridge-penalised model. The association was consistent across both centres (interaction p = 0.73). Model assumptions were satisfied (Schoenfeld p = 0.75; non-linearity p = 0.46). No subgroup interaction remained significant after false-discovery-rate correction across 17 tests. Conclusions: Elevated baseline NLR is an independent adverse prognostic marker for PFS among HER2+ ABC patients treated with T-DXd, and carries prognostic information beyond its individual blood components and beyond standard clinical variables. Because no comparator arm exists, NLR should be interpreted as a prognostic—not predictive—biomarker in this setting; prospective validation is required before any clinical application.