Pressure-driven dome-shaped superconductivity in topological insulator GeBi2Te4.

The discovery of new superconductors based on topological insulators always captures special attention due to their unique structural and electronic properties. High pressure is an effective way to regulate the lattice as well as electronic states in the topological insulators, thus altering their electronic properties. Herein, we report the structural and electrical transport properties of the topological insulator GeBi2Te4by using high-pressure techniques. The synchrotron x-ray diffraction revealed that GeBi2Te4underwent two structural phase transitions fromR-3m(phase I) toC2/m(phase II) and then intoIm-3m(phase III). Superconductivity was observed at 6.6 GPa to be associated with the first structural phase transition. The superconducting transition temperatureTcreached a maximum value of 8.4 K, accompanied by theRHsign changing from negative to positive at 14.6 GPa, then gradually decreased with increasing pressure in phase III, showing a dome-shaped phase diagram. The present results provide a platform for understanding the interplay between the crystal structure and superconductivity by the regulation of pressure in the topological insulator materials.

Exploring the clinical outcomes and safety profile of inetetamab treatment in metastatic breast cancer patients: A multicenter assessment of a Chinese-origin recombinant Anti-HER2 monoclonal antibody.

BACKGROUND: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. METHODS: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334-3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133-3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370-0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). CONCLUSION: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.

Giant Reduction of Stabilized Pressure for the Superconducting Re0.8V0.2Se2 Phase.

Access to new superconducting phases in transition-metal dichalcogenides (TMDs) via pressure treatment has been the primary target in this field. As equally essential as the fabrication of new superconducting materials at high pressure, maneuvering new superconducting phases at moderate pressures is also one of the core goals in the synthesis community. Here, we successfully reduced the synthesized pressure of the superconducting phase in ReSe2 by combining V-doping and high-pressure techniques, with a reduction in pressure of 50% in contrast to ReSe2. Our electrical transport measurements displayed that metallization appeared at 10 GPa and subsequently superconductivity appeared at about 52.4 GPa with Tc ∼ 1.9 K. There was a giant reduction in the stable pressure of the superconducting phase derived from the d-electrons and interlayer interaction changes, as evidenced by the Hall effect and X-ray diffraction measurements. These findings serve as ideal starting points and guidance for designing superconducting TMDs at moderate pressures.

Artificial intelligence scale-invariant feature transform algorithm-based system to improve the calculation accuracy of Ki-67 index in invasive breast cancer: a multicenter retrospective study.

Background: Ki-67 is a key indicator of the proliferation activity of tumors. However, no standardized criterion has been established for Ki-67 index calculation. Scale-invariant feature transform (SIFT) algorithm can identify the robust invariant features to rotation, translation, scaling and linear intensity changes for matching and registration in computer vision. Thus, this study aimed to develop a SIFT-based computer-aided system for Ki-67 calculation in breast cancer. Methods: Hematoxylin and eosin (HE)-stained and Ki-67-stained slides were scanned and whole slide images (WSIs) were obtained. The regions of breast cancer (BC) tissues and non-BC tissues were labeled by experienced pathologists. All the labeled WSIs were randomly divided into the training set, verification set, and test set according to a fixed ratio of 7:2:1. The algorithm for identification of cancerous regions was developed by a ResNet network. The registration process between paired consecutive HE-stained WSIs and Ki-67-stained WSIs was based on a pyramid model using the feature matching method of SIFT. After registration, we counted the nuclear-stained Ki-67-positive cells in each identified invasive cancerous region using color deconvolution. To assess the accuracy, the AI-assisted result for each slice was compared with the manual diagnosis result of pathologists. If the difference of the two positive rate values is not greater than 10%, it was a consistent result; otherwise, it was an inconsistent result. Results: The accuracy of the AI-based algorithm in identifying breast cancer tissues in HE-stained slides was 93%, with an area under the curve (AUC) of 0.98. After registration, we succeeded in identifying Ki-67-positive cells among cancerous cells across the entire WSIs and calculated the Ki-67 index, with an accuracy rate of 91.5%, compared to the gold standard pathological reports. Using this system, it took about 1 hour to complete the evaluation of all the tested 771 pairs of HE- and Ki-67-stained slides. Each Ki-67 result took less than 2 seconds. Conclusions: Using a pyramid model and the SIFT feature matching method, we developed an AI-based automatic cancer identification and Ki-67 index calculation system, which could improve the accuracy of Ki-67 index calculation and make the data repeatable among different hospitals and centers.

Exploration of the regulatory mechanisms of regeneration, anti-oxidation, anti-aging and the immune response at the post-molt stage of Eriocheir sinensis.

Eriocheir sinensis is widely appreciated by the surrounding population due to its culinary delicacy and rich nutrients. The E. sinensis breeding industry is very prosperous and molting is one of the important growth characteristics. Research on the regulation of molting in E. sinensis is still in the initial stages. There is currently no relevant information on the regulatory mechanisms of heart development following molting. Comparative transcriptome analysis was used to study developmental regulation mechanisms in the heart of E. sinensis at the post-molt and inter-molt stages. The results indicated that many regulatory pathways and genes involved in regeneration, anti-oxidation, anti-aging and the immune response were significantly upregulated after molting in E. sinensis. Aside from cardiac development, the differentially expressed genes (DEGs) were relevant to myocardial movement and neuronal signal transduction. DEGs were also related to the regulation of glutathione homeostasis and biological rhythms in regard to anti-oxidation and anti-aging, and to the regulation of immune cell development and the immune response. This study provides a theoretical framework for understanding the regulation of molting in E. sinensis and in other economically important crustaceans.

The prognosis and risk factors for capecitabine maintenance treatment in metastatic breast cancer: a retrospective comparative cohort study.

Background: Maintenance treatment following efficient chemotherapy can improve the treatment outcomes of patients with metastatic breast cancer (MBC). However, there are no studies for identifying the prognostic factors for patients who could benefit from capecitabine maintenance. Therefore, this study aimed to investigate the prognosis and risk factors of capecitabine maintenance therapy and analysed the circulating tumour DNA (ctDNA) markers that may be related to the treatment response. Methods: This study recruited 482 consecutive patients with MBC who achieved clinical benefit from capecitabine-based chemotherapy from 2011 to 2019. A total of 256 patients received subsequent capecitabine maintenance therapy. The baseline clinical factors included age at diagnosis, menopause, neoadjuvant therapy, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and subtypes, prior treatment lines, and prior capecitabine-based treatment response. Treatment outcome (progression-free survival, PFS) was assessed by imaging tools according to RSCIST 1.1 standard during the first two treatment cycles and every 3 weeks thereafter. Univariate and multivariate Cox proportional hazards models were used to analysethe association between capecitabine maintenance treatment and prognosis. Results: The median PFS of patients receiving capecitabine maintenance treatment was 21.7 months [95% confidence interval (CI): 15.1-36.3 months]. Capecitabine maintenance showed similar effects as endocrine maintenance or anti-HER2 therapy in hormone receptor (HR)-positive or HER2-positive patients, with adjusted HR of 1.17 (95% CI: 0.81-1.71, P=0.40). In patients with triple-negative breast cancer (TNBC), capecitabine maintenance showed a marginal benefit in PFS. Compared to late-line (≥2) capecitabine maintenance, first-line capecitabine maintenance significantly prolonged median PFS. Compared to other HR/HER2 subtypes, patients with HR-positive and HER2-positive subtypes significantly benefited from capecitabine maintenance treatment. Analysis of ctDNA revealed that among patients receiving capecitabine maintenance, TP53 aberrations were concentrated in patients with short PFS. Conclusions: Capecitabine maintenance treatment is associated with longer PFS in patients with MBC, especially those receiving first-line capecitabine-based chemotherapy and those with HR positivity/HER2 positivity. TP53 aberrations may be responsible for the poor response to capecitabine maintenance treatment.

The circulating tumor DNA (ctDNA) alteration level predicts therapeutic response in metastatic breast cancer: Novel prognostic indexes based on ctDNA.

PURPOSE: Circulating tumor DNA (ctDNA) has good clinical guiding value for metastatic breast cancer (MBC) patients. This study aimed to apply a novel genetic analysis approach for therapeutic prediction based on ctDNA alterations. METHOD: This nonrandomized, multicenter study recruited 223 MBC patients (NCT05079074). Plasma samples were collected for target-capture deep sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when progressive disease (PD) was evaluated. Samples were categorized into four levels according to the number of ctDNA alterations: level 1 (no alterations), level 2 (1-2 alterations), level 3 (3-4 alterations) and level 4 (≥5 alterations). According to ctDNA alteration level and variant allele frequency (VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors (ctle-RECIST) was established to assess treatment response and predict progression-free survival (PFS). RESULTS: The median PFS in level 1 (6.63 months) patients was significantly longer than that in level 2-4 patients (level 2: 5.70 months; level 3-4: 4.90 months, p < 0.05). After 2 cycles of treatment, based on ctle-RECIST, the median PFS of level-based disease control rate (lev-DCR) patients was significantly longer than that of level-based PD (lev-PD) patients [HR 2.42 (1.52-3.85), p < 0.001]. In addition, we found that ctDNA level assessment could be a good supplement to radiologic assessment. The median PFS in the dual-DCR group tended to be longer than that in the single-DCR group [HR 1.41 (0.93-2.13), p = 0.107]. CONCLUSION: The ctDNA alteration level and ctle-RECIST could be novel biomarkers of prognosis and could complement radiologic assessment in MBC.

Subtyping of metastatic breast cancer based on plasma circulating tumor DNA alterations: An observational, multicentre platform study.

Background: After multiple lines of therapies, no guideline or consensus is currently available for the treatment of patients with metastatic breast cancer. This study aims to evaluate the efficacy of a novel re-subtyping and treatment strategy based on ctDNA alterations. Methods: This observational, multicentre study recruited 223 patients with metastatic breast cancer intending to receive late-line therapy from Dec 1, 2016, to June 31, 2019. This study took place in Hunan Cancer Hospital, the Forth Hospital of Changsha and Zhuzhou Central Hospital in China. ctDNA alterations were assessed by next-generation sequencing (NGS). Patients with druggable ctDNA alterations were treated with corresponding targeted drugs which are clinically available. Other patients received physician-chosen treatment. This study was registered with ClinicalTrials.gov, NCT05079074. Findings: The progression-free survival (hazard ratio: 0.45, 95% Confidence Interval (CI): 0.33-0.62, P < 0.0001) and disease control rate (89.4% vs. 65.9%, P < 0.0001) were significantly improved in patients who received druggable ctDNA alteration-guided therapy compared with those of patients who received physician-chosen treatment. ctDNA alterations with top rank and high clustering scores were classified into four subtypes based on their functions as follows: 1) extracellular function (ECF), 2) cell proliferation (CP), 3) nuclear function (NF), and 4) cascade signaling pathway (CSP). A significant benefit from ctDNA alteration-guided treatment was observed in patients with NF and CSP ctDNA alterations, with hazard ratios of 0.39 (95% CI: 0.24-0.65, P = 0.0003) and 0.14 (95% CI: 0.04-0.46, P < 0.0001), respectively. Interpretation: After multiline traditional pathological HR/HER2 subtype-guided therapies, ctDNA testing could identify druggable ctDNA alterations to guide late-line therapy for patients with metastatic breast cancer. Funding: This work was supported by Key Grants of Research and Development in Hunan Province (2018SK2124, 2018SK2120), Natural Science Foundation of Hunan (2019JJ50360), Hunan Provincial Health Commission Project (B2019085, B2019089 and C2019070), and Changsha Science and Technology Project (kq2004125 and kq2004137).

Recognition of Gonadal Development in Eriocheir sinensis Based on the Impulse of Love at First Sight.

Given the difficulty in identifying individuals with different degrees of ovarian development, we developed a new device utilizing the hypothesis of mutual attraction behavior between male and female crabs with mature gonads by releasing the sexual pheromone so they could be examined. From a total of 40 female crabs, 10 were isolated within half an hour. Histological analysis showed that the ovaries of crabs in the isolated group were in stage IV, while those of the control groups were in stage III. In addition, progesterone (PROG) in experimental groups was significantly reduced compared with the control group (p < 0.05), but no significant difference was detected in estradiol (E2). In response to the different developmental stages, hemolymph biochemical indices and the determination of gonadal fatty acids profiles were explored. The results indicated only C18:4 showed a significant difference between these two groups. A transcriptome was generated to determine the genes involved in the mutual attraction process; differentially expressed genes (DEGs) were significantly related to gonadal development. Therefore, the device can be used to isolate Chinese mitten crabs with stage IV ovarian development.

Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 in TP53-Aberrant Triple-Negative Breast Cancer.

Background: In triple-negative breast cancer (TNBC), PDL1/PD1-directed immunotherapy is effective in less than 20% of patients. In our preliminary study, we have found CSPG4 to be highly expressed together with PDL1 in TNBCs, particularly those harboring TP53 aberrations. However, the clinical implications of co-expressed CSPG4 and PDL1 in TNBCs remain elusive. Methods: A total of 85 advanced TNBC patients treated in the Hunan Cancer Hospital between January 2017 and August 2019 were recruited. The expressions of CSPG4 and PDL1 in TNBC tissues were investigated using immunohistochemistry (IHC). The RNA-seq dataset from the TCGA-BRCA project was further used to analyze the mRNA expression of CSPG4 and PDL1 in TP53-aberrant TNBCs. Cox proportional hazards model and Kaplan-Meier curves with Logrank test was used to analyze the effects of CSPG4 and PDL1 on survival. TNBC cell lines were further used to investigate the molecular mechanism that were involved. Results: TP53 aberrations occurred in more than 50% of metastatic TNBCs and were related to higher tumor mutation burden (TMB). In TCGA-BRCA RNA-seq dataset analysis, both CSPG4 and PDL1 levels were high in TNBCs, especially in TP53-aberrant TNBCs. IHC assay showed nearly 60% of advanced TNBCs to be CSPG4-positive and about 25% to be both CSPG4-positive and PDL1-positive. The levels of CSPG4 and PDL1 were high in TNBC cell lines as revealed by flow cytometry and immunoblotting compared with non-TNBC cells. Univariate Cox regression analysis indicated that CSPG4 positivity was a significant risk factor for progression-free survival in metastatic TNBCs, with a hazard ratio (HR) of 2.26 (P = 0.05). KM curves with Logrank test also identified high level of CSPG4 as a significant risk factor for overall survival in advanced breast cancers in TCGA-BRCA samples (P = 0.02). The immunoblotting assays showed that EMT-related pathways were involved in CSPG4-mediated invasion. Conclusions: CSPG4 expression level is associated with PDL1 positivity in TP53-aberrant TNBC cells. Patients with CSPG4 expression have poor treatment response and poor overall survival. Co-expressed CSPG4 and PDL1 may have an important prognostic value and provide new therapeutic targets in TNBC patients. CSPG4 might mediate tumor invasion and PDL1 overexpression through EMT-related pathway.

Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain.

Cancer pain (CP) is one of the most common symptoms affecting life quality, and there is considerable variation in pain experience among patients with malignant tumors. Previously, it has been found that the fluid drainage function in the brain can be regulated by peripheral pain stimulation. However, the relationship between cancer pain and functional changes of the glymphatic system (an important pathway for fluid drainage in the brain) remains unclear. In this study, 97 participants were enrolled, which included 40 participants in the cancer pain (CP) group, 27 participants in the painless cancer (PLC) group and 30 participants in the control (NC) group. Differences in glymphatic system function among the three groups and between before and after pain pharmacological intervention were analyzed by measuring diffusivity and the index along the perivascular space (ALPS index) using diffusion tensor imaging. We found that diffusivity and the ALPS index were significantly lower in the CP group than in the PLC and NC group and increased following intervention with pain relief. Moreover, the ALPS index was negatively correlated with the degree of pain in the CP group. The present study verified that alterations in glymphatic function are closely related to cancer pain, and the quantification of functional changes reflects pain severity. Our findings support the use of neuroimaging biomarkers for cancer pain assessment and indicate that pain can be alleviated by regulating brain function status.

Real-World First-Line Treatment Patterns and Outcomes in Hormone Receptor-Positive Advanced Breast Cancer Patients: A Multicenter, Retrospective Study in China.

Background: Recent data on first-line treatment patterns administered to hormone receptor-positive (HR+) advanced breast cancer (ABC) patients in the real-world setting are limited. This study aimed to report the first-line treatment patterns and outcomes of HR+ ABC patients in China. Methods: This was a multicenter, noninterventional study. Eligible patients were cytologically or histologically confirmed to have HR+ ABC with ≥2 complete medical records and received first-line therapies between January 2015 and June 2019. Treatment patterns and outcomes were extracted from structured or unstructured electronic medical records. Progression-free survival (PFS) was analyzed with the Kaplan-Meier method. Results: In total, 1072 patients with HR+ ABC were enrolled at 6 treatment sites: 327 human epidermal growth factor receptor 2-positive (HER2+) patients, 696 HER2-negative (HER2-) patients and 49 HER2-unknown patients. Overall, 62.41% of patients received first-line chemotherapy (CT), 21.08% received targeted therapy (TT) and 15.49% received endocrine therapy (ET). For HR+/HER2+ patients, 65.14% received TT, 28.44% received CT, and 5.81% received ET. Compared with patients who received TT, patients who received CT alone, had a significantly worse median PFS (adjusted hazard ratio [HR] =2.59, 95% confidence interval [CI], 1.64-4.10, p<0.001). For HR+/HER2- patients, 77.01% received CT, 20.69% received ET and 1.15% received TT. Compared with patients who received ET, patients who received CT with maintenance therapy had a significantly prolonged median PFS (adjusted HR =0.57, 95% CI, 0.44-0.76, p<0.001). Among HR+/HER2- patients who received CT with maintenance treatment, those with maintenance ET had a longer median PFS than those with maintenance CT, but the difference was not significant (adjusted HR=0.92, 95% CI, 0.64-1.33, p=0.66). Conclusions: This real-world study demonstrates that CT remains the mainstream first-line treatment option for HR+ patients in China. Among patients with HR+/HER2+ ABC, the majority received first-line TT and experienced a PFS benefit. A high percentage of HR+/HER2- patients received CT as first-line therapy in clinical practice. PFS benefit was significantly longer in patients who received CT with maintenance therapy. Moreover, there was no obvious difference in PFS between maintenance ET and CT. Maintenance ET may be a better choice considering its lower toxicity and better quality of life.

Impact of surgical management of primary tumors in stage IV breast cancer patients: a retrospective observational study based on SEER database.

OBJECTIVES: Although primary tumour surgery could prolong survival for patients with stage IV breast cancer, how to select candidates for primary tumour surgery is still a challenging problem for medical oncologists. DESIGN: This study is a retrospective database study. SETTING AND PARTICIPANTS: In this study, we aimed at evaluating the primary site surgery effect and select the beneficial subgroups. 13 618 patients with stage IV breast cancer, diagnosed between 2010 and 2015, were collected from SEER*Stat database. INTERVENTIONS: Based on the local surgery at primary tumour site, patients were categorised into three groups: primary tumour surgery performed group, recommended for primary tumour surgery but refused (RBR) group and surgery not recommended (NR) group. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause survival and breast cancer-specific survival (BCSS). RESULTS: Univariate Cox regression analyses showed that, compared with surgery group, patients in non-surgery (RBR and NR) groups tend to be older, T4, N0/NX, triple-negative and visceral metastatic. For both all-cause survival and BCSS, non-surgery, advanced T stage, triple-negative BC (TNBC) and visceral metastases were significant risk factors. Primary tumour surgery showed benefits for both all-cause survival (HR=0.44, 95% CI=0.39-0.49, p<0.0001) and BCSS (HR=0.43, 95% CI=0.38-0.49, p<0.0001). However, after propensity score matching, primary tumour surgery failed to demonstrate significant benefits for TNBC (HR=0.96, 95% CI=0.60-1.53, p=0.851) and patients with visceral metastases (HR=0.90, 95% CI=0.60-1.36, p=0.62). CONCLUSION: Surgery was associated with prolonged survival in stage IV breast cancers, but not in patients with TNBC and visceral metastases.

Complete response to pyrotinib combined with letrozole as first-line treatment of HER2-positive/HR-positive breast cancer: a case report.

Approximately 15-20% of breast cancer patients are epidermal growth factor receptor 2 (HER2)-positive, and about half of these are also hormone receptor (HR)-positive. The mainstay treatment for HER2-positive/HR-positive patients is anti-HER2 treatment combined with chemotherapy. However, many patients are not suitable for this treatment regimen due to their poor physical health and inability to tolerate chemotherapy. Pyrotinib is a novel, irreversible tyrosine kinase inhibitor (TKI) with activity against EGFR/HER1, HER2, and HER4. Several studies have shown pyrotinib's anti-tumor activity and safety profile in treating HER-2 positive breast cancer patients, but its effect on metastatic breast cancer (MBC) when combined with letrozole as a first-line treatment remains to be verified. Here, we present a case of a 50-year-old postmenopausal HER2-positive/HR-positive breast cancer patient who received pyrotinib plus letrozole as a first-line treatment following a diagnosis of left axillary lymph node and double lung metastases after modified radical mastectomy for left breast cancer. Two months after administration of combined pyrotinib and letrozole, a complete response (CR) was confirmed by CT scan. The patient experienced only mild and tolerable adverse events. At the time of writing, the patient was still alive without any recurrence. Our case indicates that the combined therapy of pyrotinib plus letrozole may/can be a promising treatment option for patients with HER2-positive/HR-positive MBC. Nevertheless, further evidence is needed to verify this conclusion.

Comparative Analysis of the Intermolt and Postmolt Hepatopancreas Transcriptomes Provides Insight into the Mechanisms of Procambarus clarkii Molting Process.

In the present study, we used RNA-Seq to investigate the expression changes in the transcriptomes of two molting stages (postmolt (M) and intermolt (NM)) of the red swamp crayfish and identified differentially expressed genes. The transcriptomes of the two molting stages were de novo assembled into 139,100 unigenes with a mean length of 675.59 bp. The results were searched against the NCBI, NR, KEGG, Swissprot, and KOG databases, to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. Furthermore, using the DESeq R package, differentially expressed genes were evaluated. The analysis revealed that 2347 genes were significantly (p > 0.05) differentially expressed in the two molting stages. Several genes and other factors involved in several molecular events critical for the molting process, such as energy requirements, hormonal regulation, immune response, and exoskeleton formation were identified and evaluated by correlation and KEGG analysis. The expression profiles of transcripts detected via RNA-Seq were validated by real-time PCR assay of eight genes. The information presented here provides a transient view of the hepatopancreas transcripts available in the postmolt and intermolt stage of crayfish, hormonal regulation, immune response, and skeletal-related activities during the postmolt stage and the intermolt stage.

A case of a vaginal Brenner tumor without a gland mimicking a borderline tumor: unusual morphology and diagnostic pitfalls.

Brenner tumor is a rare neoplasm of the vagina. This tumor is diagnosed according to the criteria of ovarian tumors. We report here a 64-year-old postmenopausal woman with a 2.0-cm sessile vaginal polyp for 9 years. Microscopic examination showed unusual features of no gland appearing in the tumor, but the other two characteristic components of transitional islands and dense fibrous stroma were observed. The tumor was diagnosed as a vaginal Brenner tumor on the basis of the definition proposed by the World Health Organization classification of female reproductive organ tumors. In our case, part of the epithelial nests of the Brenner tumor showed basaloid cell differentiation with peripheral palisading, and irregular papillary hyperplasia was observed around the epithelial nests similar to a borderline tumor. However, no mitotic activity or nuclear atypia was present in either the epithelial or stromal components. The presence of epithelial nests requires attention in the medical history of the patient. Our patient did not have a history of primary urothelial carcinoma. Our patient's benign vaginal Brenner tumor with different morphological characteristics supports the current notion that Walthard nests might act as possible precursor lesions.

FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients.

BACKGROUND: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. METHOD: We designed a real-world study to investigate using patients' clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. RESULTS: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor (FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. CONCLUSION: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

In Vivo Detection of CTC and CTC Plakoglobin Status Helps Predict Prognosis in Patients with Metastatic Breast Cancer.

This study aims to detect the prognostic value of circulating tumour cell (CTC) in patients with metastatic breast cancer. In this study, 38 patients with metastatic breast cancer were enrolled. The in vivo CellCollector® method was used to detect the number of CTC in patients. Single CTC and CTC clusters were counted, and the expression of plakoglobin was also analysed. At baseline, 73.7% (28/38) of the patients were positive for ≥ 1 CTC (range, 1-14 cells). No CTC-like events were observed in the control group. Among the CTC-positive patients, 21.4% (6/28) of patients had CTC clusters, and 42.9% (12/28) of patients had plakoglobin-positive CTC. After chemotherapy, 48.6% (17/35) of the patients were positive for ≥ 1 CTC (range, 1-3 cells), of which 3 patients had CTC clusters, and 35.3% (6/17) had plakoglobin-positive CTC. Additionally, we found that the number of CTC clusters in plakoglobin-positive patients was much greater than that in plakoglobin-negative patients, and the number of CTC was associated with the number of sites of metastases. We also found that patients with ≥ 3 CTC at baseline had shorter progression-free survival (PFS) and overall survival (OS), and pre-chemotherapy CTC detection was associated with PFS (P = 0.0001) and OS (P = 0.0091). CTC plakoglobin expression was associated with PFS (P = 0.02) but not OS (P = 0.22). CTC collected by the in vivo CellCollector method in Chinese patients with metastatic breast cancer have prognostic significance. CTC plakoglobin expression may be associated with CTC clusters, and more in-depth studies are needed.

PIK3CA gene mutations in the helical domain correlate with high tumor mutation burden and poor prognosis in metastatic breast carcinomas with late-line therapies.

Nearly half of metastatic breast cancers (MBC) have genetic aberrations in the PI3K/AKT pathway. To investigate the distinct effect of these aberrations on MBC, 193 MBC patients who progressed after the early line (≤2) salvage treatment voluntarily received next generation sequencing (NGS) for a panel of 1,021 genes. 93 (48%) patients had genetic aberrations in the PI3K/AKT pathway. The number of patients with PIK3CA mutations in kinase domain (KD), helical domain (HD) and other domain (OD), were 36 (18.7%), 26 (13.5%), 10 (5.2%), respectively. 21 (10.9%) patients had mutations in PI3K/AKT pathway genes other than PIK3CA (P/A). Compared to PI3K/AKT-wild type (WT) patients, PIK3CA-HD patients had a significantly shorter progression-free survival (PFS) (Logrank p-value < 0.0001). PIK3CA-KD, PIK3CA-OD and other P/A mutations showed similar PFS to WT patients (Logrank p-value = 0.63). PIK3CA-HD patients had a distinct ctDNA mutation profile to patients with other PI3K/AKT mutations. PIK3CA-HD patients had a higher rate of FGFR and NF1 aberrations. In addition, more PIK3CA-HD carriers were TMB-high. Cox regression analyses suggested that PIK3CA-HD mutations, FGFR aberrations and high TMB were all significant risk factors for poor PFS. In conclusion, future research needs to focus more on the treatment strategies targeting PIK3CA-HD mutations.