Background: Our retrospective study in breast cancer patients evaluated whether integrating subtype and pathologic complete response (pCR) information into axillary lymph node restaging after neoadjuvant chemotherapy (NAC) adds significance to its prognostic values. Methods: Patients included in the analysis had stage II or III disease, with post-NAC axillary lymph node dissection (ALND), without sentinel lymph node biopsy before completion of NAC, with definitive subtyping data and subtype-oriented adjuvant treatments. The ypN grading system was used to restage axillary lymph node status, and ypN0 was adjusted by pCR in both breast and axilla into ypN0(pCR) and ypN0(non-pCR). Univariate and multivariate survival analyses were performed. Results: Among the 301 patients analyzed, 145 had tumours that were hormone receptor–positive (HR+) and negative for the human epidermal growth factor receptor (HER2–), 101 had tumours that were positive for HER2 (HER2+), and 55 had tumours that were triple-negative. The rate of pCR in both breast and axilla was 11.7%, 43.6%, and 25.5% respectively for the 3 subtypes. Compared with the non-pCR patients, the pCR patients had better disease-free survival (DFS) and overall survival (OS): p = 0.002 for DFS and p = 0.011 for OS. In non-pCR patients, DFS and OS were similar in the ypN0(non-pCR) and ypN1 subgroups, and in the ypN2 and ypN3 subgroups. We therefore grouped the ypN grading results into ypN0(pCR) (n = 75), ypN0– 1(non-pCR) (n = 175), and ypN2–3 (n = 51). In those groups, the 3-year DFS was 98%, 91%, and 56%, and the 3-year OS was 100%, 91%, and 82% respectively. The differences in DFS and OS between those three subgroups were significant (all p < 0.05 in paired comparisons). Multivariate Cox regression showed that subtype and ypN staging adjusted by pCR were the only two independent factors predicting DFS. Conclusions: Axillary lymph node status after NAC, adjusted for pCR in breast and axilla, predicts differential DFS in patients without prior sentinel lymph node biopsy.

Breast cancer (BC) is characterized by high morbidity. Mitochondrial ribosomal protein (MRP) family participates in mitochondrial energy metabolism, underlying BC progression. This study aims to analyze the expression and prognosis effect of the MRP genes in BC patients. GEPIA2, UALCAN, cBioPortal, and MethSurv were used to demonstrate the differential expression, genomic alteration profiles, and DNA methylation of the MRP gene family in BC. Functional enrichment analysis and protein–protein interaction network construction were performed to understand the biological function. Based on 1056 TCGA samples with the transcriptional level of MRPs, Kaplan–Meier curves, Cox, and LASSO regression were applied to explore their prognostic effects. 12 MRPs were upregulated in BC, which were associated with gene amplification and DNA methylation. MRP genetic alteration occurred in 42% of BC patients, and amplification was the most frequent variation. Functioning in its entirety, the MRP family was involved in mitochondrial translational termination, elongation, translation, and poly(A) RNA binding. High expression of MRPL1, MRPL13, MRPS6, MRPS18C, and MRPS35, as well as low levels of MRPL16, and MRPL40 significantly indicated poor prognosis in BC patients. Thus, a novel MRP-based prognostic nomogram was established and verified with favorable discrimination and calibration. We not only provided a thorough expression and prognosis analysis of the MRP family in BC patients but also constructed an MRP-based prognostic nomogram. It was suggested that MRPs acted as biomarkers in individualized risk prediction and may serve as potential therapeutic targets in BC patients.

Background: Recent studies have shown that selenium-binding protein 1 (SELENBP1) is significantly down-regulated in a variety of solid tumors. Nevertheless, the clinical relevance of SELENBP1 in human bladder cancer has not been described in any detail, and the molecular mechanism underlying its inhibitory role in cancer cell growth is largely unknown. Methods: SELENBP1 expression levels in tumor tissues and adjacent normal tissues were evaluated using immunoblotting assay. The association of SELENBP1 expression, clinicopathological features, and clinical outcome was determined using publicly available dataset from The Cancer Genome Atlas bladder cancer (TCGA-BLCA) cohort. DNA methylation in SELENBP1 gene was assessed using online MEXPRESS tool. We generated stable SELENBP1-overexpression and their corresponding control cell lines to determine its potential effect on cell cycle and transcriptional activity of p21 by using flow cytometry and luciferase reporter assay, respectively. The dominant-negative mutant constructs, TAM67 and STAT1 Y701F, were employed to define the roles of c-Jun and STAT1 in the regulation of p21 protein. Results: Here, we report that the reduction of SELENBP1 is a frequent event and significantly correlates with tumor progression as well as unfavorable prognosis in human bladder cancer. By utilizing TCGA-BLCA cohort, DNA hypermethylation, especially in gene body, is shown to be likely to account for the reduction of SELENBP1 expression. However, an apparent paradox is observed in its 3′-UTR region, in which DNA methylation is positively related to SELENBP1 expression. More importantly, we verify the growth inhibitory role for SELENBP1 in human bladder cancer, and further report a novel function for SELENBP1 in transcriptionally modulating p21 expression through a p53-independent mechanism. Instead, ectopic expression of SELENBP1 pronouncedly attenuates the phosphorylation of c-Jun and STAT1, both of which are indispensable for SELENBP1-mediated transcriptional induction of p21, thereby resulting in the G₀/G₁ phase cell cycle arrest in bladder cancer cell. Conclusions: Taken together, our findings provide clinical and molecular insights into improved understanding of the tumor suppressive role for SELENBP1 in human bladder cancer, suggesting that SELENBP1 could potentially be utilized as a prognostic biomarker as well as a therapeutic target in future cancer therapy.

Lin X, et al. J Breast Cancer. 2023 Jul;26:e30. https://doi.org/10.4048/jbc.2023.26.e30

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: Both TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well‐characterized.Methods: A total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next‐generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse‐free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy.Results: In GDPH cohort, patients with TP53/MYC co‐alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF‐β signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019–14.579; p < 0.001). They maintained independent significance for relapse‐free (HR, 1.310; 95% CI: 1.012–1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093–1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553–25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088–0.788; p = 0.020) were associated with pCR, while the co‐alteration did not serve as an independent predictor (p = 0.199).Conclusions: TP53/MYC co‐alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.