Guochun Zhang

Rationale: Triple-negative breast cancer (TNBC) with germline PALB2 (gPALB2 ) mutations represents a rare but actionable subset sensitive to poly(ADP-ribose) polymerase (PARP) inhibition. However, clinical evidence supporting PARP inhibition combined with programmed cell death protein 1 (PD-1) blockade after progression on prior immunotherapy remains limited, particularly in central nervous system-involved disease. Patient concerns: A 61-year-old woman initially diagnosed with stage I TNBC developed chest wall recurrence and occipital bone metastasis after a 2-year disease-free interval. The disease subsequently progressed to spinal leptomeningeal metastasis, causing complete bilateral lower-limb paralysis. Diagnoses: Recurrent metastatic TNBC with programmed death-ligand 1 expression and leptomeningeal and multiple osseous metastases was diagnosed. Pharmacogenomic profiling identified a pathogenic gPALB2 p.L484* mutation. Interventions: First-line liposomal doxorubicin achieved 9 months of disease control. Second-line nab-paclitaxel plus tislelizumab, a PD-1 inhibitor, provided a progression-free survival of only 2 months. Third-line carboplatin plus tislelizumab induced rapid neurological improvement, but carboplatin was discontinued after 2 months due to hematologic toxicity. Maintenance tislelizumab monotherapy was continued for an additional 5 months until neurological deterioration and a new femoral metastasis indicated disease progression. Olaparib was subsequently added to continued tislelizumab. Outcomes: Following olaparib initiation, bilateral lower-limb muscle strength improved from Medical Research Council grade 0 to grade 2. Follow-up imaging demonstrated marked regression of the leptomeningeal and osseous lesions. The patient achieved a durable progression-free survival of approximately 40 months with acceptable tolerability. Lessons: Identification of a gPALB2 mutation informed the addition of olaparib to continued tislelizumab, leading to sustained disease control in this patient. Although the relative contributions of each component cannot be determined from a single case, this hypothesis-generating observation suggests that PARP inhibitor–based strategies and continuation of PD-1 blockade beyond progression warrant further investigation in carefully selected patients with gPALB2 -mutated TNBC with central nervous system involvement.

Background: Although next-generation sequencing (NGS) has been widely used to provide comprehensive somatic mutational information for individualized therapy in breast cancer patients, whether or not it could reliably evaluate HER2 status to guide targeted therapy when compared to the current IHC/FISH standard criteria still lacks sufficient validations. Methods: We analyzed the clinicopathological and NGS somatic genomic data of 1,171 Chinese breast cancer patients. A commercial 520 gene panel was used to generate genomic variation data by NGS in breast cancer samples. We compared the concordance of HER2 status between NGS evaluation and IHC/FISH criteria. We further defined the amplification status of HER2 based on the length of amplification region beginning from ERBB2 and extending to adjacent genes by focal (1 megabase) amplification and stratified the cohort accordingly to investigate its potential in predicting efficacy of trastuzumab-based neoadjuvant therapy. Results: NGS showed high concordance with FISH/IHC-defined HER2 status with a sensitivity of 95.7%, specificity of 94.2%, and overall concordance rate of 94.9%. NGS characterized the genomic landscape of enrolled patients, identifying frequent mutations including TP53, ERBB2, PIK3CA, CDK12, MYC, and CCND1. The focal amplification subgroup exhibited significantly higher gene copy number (GCN) (31.7 vs 10.2, p < 0.001), greater HER2 positivity rates (98.3% vs. 78.3%, p < 0.001), higher IHC 3+ prevalence (91.7% vs. 48.5%, p < 0.001) and increased FISH + proportion (98.5% vs. 77.9%, p < 0.001). In patients receiving HER2-targeted neoadjuvant therapy, the focal amplification group had a higher pCR rate compared with broad amplification group (46.0% vs. 20.0%, p = 0.031). Conclusion: NGS demonstrates comparable capability to IHC/FISH in HER2 status interpretation and provides additional genomic information. Higher HER2 NGS copy numbers and focal amplification may be associated with a higher pCR rate.

Background: Precise surgical excision of nonpalpable breast microcalcifications remains challenging when conventional localization equipment is limited or not routinely available across clinical settings, underscoring the need for an accessible and reproducible alternative approach. This study aimed to assess the feasibility and localization accuracy of a novel mammography-based localization strategy for guiding diagnostic surgical excision of nonpalpable breast microcalcifications. Methods: This multicenter retrospective study evaluated a mammography-based geometric localization approach termed mammogram geometric projection localization (MaGPL). The technique applies a boundary-defined, range-based “Maximal Width Crossing Criterion” to reconstruct a body-surface coordinated field from two standard mammographic projections, preferentially the craniocaudal (CC) and lateromedial (LM) views. By deliberately selecting the most geometrically stable boundary information from each projection, MaGPL defines axis-specific localization boundaries, forming the geometric basis for boundary-defined localization of nonpalpable calcifications. A total of 41 patients (45 lesions) underwent diagnostic excision guided by MaGPL. Localization accuracy was evaluated using the geometric offset (D_offset), defined as the linear distance between the radiographic center of the calcification cluster and the center of the excised specimen measured on intraoperative mammography. Results: The cohort had a median age of 48 years (range, 25–81 years) and a mean mammographically estimated breast volume of 370±158 mL. The mean linear extent of the target calcification clusters was 22.6±15.1 mm (range, 3.0–67.0 mm), and pathologic examination confirmed malignancy in 18 of 45 lesions (40.0%). All calcification clusters were successfully excised in a single operation, achieving a 100% intraoperative retrieval rate. The median D_offset was 9.7 mm [interquartile range (IQR), 8.3–13.0 mm], indicating a clinically acceptable level of geometric localization precision. Orthogonal CC + LM projections yielded smaller offsets than non-orthogonal combinations (P=0.003). Larger breast volumes were associated with greater D_offset (PConclusions: MaGPL represents a standardized, equipment-independent alternative for body-surface localization to guide surgical excision of nonpalpable breast microcalcifications, offering reproducible and clinically applicable localization accuracy without additional cost, with particular utility in community and resource-limited settings.

Germline mutations were evaluated in 530 Chinese breast cancer (BC) patients with different HER2 expression status plus 98 patients with atypical ductal hyperplasia or a breast cancer family history. DNA extracted from blood samples was analyzed with a next generation sequencing based multigene panel, with reporting of likely pathogenic and pathogenic variants (PV) of 102 cancer associated genes, and correlation between clinicopathologic characteristics and known BC-associated genes. The 71 identified PVs were categorized into five distinct pathway clusters: BRCA/FANC, DDR, HRR, FANC, and Other. The distribution of PVs enriched within these clusters differed significantly between BC patients and unaffected individuals (p = 0.031). This difference was primarily driven by the BRCA/FANC, FANC, and DDR clusters, with enrichment percentages of 57.7% vs. 16.7% (BRCA/FANC), 7.0% vs. 25.0% (FANC), and 15.5% vs. 41.7% (DDR) in BC vs. unaffected groups, respectively. Notably, the three BC groups stratified by HER2 expression level exhibited distinct PV distributions. Both the HER2-low and HER2-zero BC groups showed significantly different distributions compared to unaffected individuals (p = 0.0132 and p = 0.0081, respectively). The BRCA/FANC cluster was the predominant pathway enriched in both HER2-low (59.6%) and HER2-zero (81.8%) groups. Furthermore, the PV distribution in the HER2-zero group was significantly different from that in the HER2-high group (p = 0.0028). In contrast, the distribution in the HER2-high group resembled that observed in non-BC individuals. These findings indicate that BC patients with different HER2 expression statuses harbor distinct germline PV signatures, which correlate with differential clinical outcomes following neoadjuvant systemic therapy. Chinese breast cancer patients with different HER2 expression status demonstrated different pathogenic germline variant, which correlated with different clinical outcome after neoadjuvant therapy. Multi-gene genetic testing for pathogenic germline variants may be considered for breast cancer patients and high-risk individuals who could benefit from prevention and early detection programs. The online version contains supplementary material available at10.1007/s12672-026-05037-6.

PURPOSE: We assessed the accuracy and reproducibility of Chat Generative Pre-Trained Transformer's (ChatGPT) recommendations in response to breast cancer patients by comparing generated outputs with consensus expert opinions. METHODS: 362 consecutive breast cancer patients sourced from a weekly international breast cancer webinar series were submitted to a tumor board of renowned experts. The same 362 clinical patients were also prompted to ChatGPT-4.0 three separate times to examine reproducibility. RESULTS: Only 46% of ChatGPT-generated content was entirely concordant with the recommendations of breast cancer experts, and only 39% of ChatGPT's responses demonstrated inter-response similarity. ChatGPT's responses demonstrated higher concordance with CEN experts in earlier stages of breast cancer (0, I, II, III) compared to advanced (IV) patients ( P = .019). There were less accurate responses from ChatGPT when responding to patients involving molecular markers and genetic testing ( P = .025), and in patients involving antibody drug conjugates ( P = .006). ChatGPT's responses were not necessarily incorrect but often omitted specific details about clinical management. When the same prompt was independently sent to CEN into the model on three occasions, each time by difference users, ChatGPT's responses exhibited variable content and formatting in 68% (246 out of 362) of patients and were entirely consistent with one another in only 32% of responses. CONCLUSION: Since this promising clinical decision-making support tool is widely used currently by physicians worldwide, it is important for the user to understand its limitations as currently constructed when responding to multidisciplinary breast cancer patients, and for researchers in the field to continue improving its ability with contemporary, accurate and complete breast cancer information. As currently constructed, ChatGPT is not engineered to generate identical outputs to the same input and was less likely to correctly interpret and recommend treatments for complex breast cancer patients.

Background: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant‐based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta‐analysis to evaluate its risks and benefits in IBBR comparing with other meshes.Methods: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well‐being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated.Results: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32–0.86), seroma (RR = 0.21, 95% CI, 0.07–0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02–0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05–0.75). Patient satisfaction in physical well‐being was comparable between two groups.Conclusions: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well‐designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.