Automated System to Capture Patient Symptoms From Multitype Japanese Clinical Texts: Retrospective Study.

BACKGROUND: Natural language processing (NLP) techniques can be used to analyze large amounts of electronic health record texts, which encompasses various types of patient information such as quality of life, effectiveness of treatments, and adverse drug event (ADE) signals. As different aspects of a patient's status are stored in different types of documents, we propose an NLP system capable of processing 6 types of documents: physician progress notes, discharge summaries, radiology reports, radioisotope reports, nursing records, and pharmacist progress notes. OBJECTIVE: This study aimed to investigate the system's performance in detecting ADEs by evaluating the results from multitype texts. The main objective is to detect adverse events accurately using an NLP system. METHODS: We used data written in Japanese from 2289 patients with breast cancer, including medication data, physician progress notes, discharge summaries, radiology reports, radioisotope reports, nursing records, and pharmacist progress notes. Our system performs 3 processes: named entity recognition, normalization of symptoms, and aggregation of multiple types of documents from multiple patients. Among all patients with breast cancer, 103 and 112 with peripheral neuropathy (PN) received paclitaxel or docetaxel, respectively. We evaluate the utility of using multiple types of documents by correlation coefficient and regression analysis to compare their performance with each single type of document. All evaluations of detection rates with our system are performed 30 days after drug administration. RESULTS: Our system underestimates by 13.3 percentage points (74.0%-60.7%), as the incidence of paclitaxel-induced PN was 60.7%, compared with 74.0% in the previous research based on manual extraction. The Pearson correlation coefficient between the manual extraction and system results was 0.87 Although the pharmacist progress notes had the highest detection rate among each type of document, the rate did not match the performance using all documents. The estimated median duration of PN with paclitaxel was 92 days, whereas the previously reported median duration of PN with paclitaxel was 727 days. The number of events detected in each document was highest in the physician's progress notes, followed by the pharmacist's and nursing records. CONCLUSIONS: Considering the inherent cost that requires constant monitoring of the patient's condition, such as the treatment of PN, our system has a significant advantage in that it can immediately estimate the treatment duration without fine-tuning a new NLP model. Leveraging multitype documents is better than using single-type documents to improve detection performance. Although the onset time estimation was relatively accurate, the duration might have been influenced by the length of the data follow-up period. The results suggest that our method using various types of data can detect more ADEs from clinical documents.

Examination of the Suitability of Vericiguat in Non-Heart Failure with Preserved Ejection Fraction Patients with Improved Ejection Fraction.

Background/Objectives: Vericiguat has been shown to reduce cardiovascular mortality and hospitalisation for heart failure in patients with reduced ejection fraction. While Vericiguat is considered one of the standard treatments for heart failure, it is unclear under which conditions Vericiguat would be most effective. With a focus on the prognosis and improved EF of heart failure, we aimed to investigate in which cases Vericiguat is suitable for use in addition to standard cardioprotective drugs. Methods: We prospectively compared echocardiograms taken before and after the administration of Vericiguat in 46 patients with non-dialysis and without heart failure with preserved ejection fraction (non-HFpEF) (left ventricle ejection fraction [LVEF] < 50%) who were able to continue Vericiguat in addition to other standard heart failure drugs (the "Fantastic Four") for more than 6 months at our hospital. Patients who showed an improvement of 10 points or more in LVEF were defined as improved EF+. Results: LVEF improved significantly from 38 [33-45]% at the time of administration to 46 [35-54.5]% at 6 months (p < 0.001). When comparing patients with and without improved EF, a significant difference was observed in the Hb (OR = 1.66, 95%CI = 1.12-2.83, p = 0.028), early introduction (OR = 12.5, 95%CI = 1.58-149, p = 0.025), and initiation of Vericiguat after the administration of the Fantastic Four (OR = 9.79, 95%CI = 1.71-100.2, p = 0.022). Conclusions: In this study, the early administration of Vericiguat, haemoglobin value, and initiation of Vericiguat after the introduction of the Fantastic Four were identified as independent factors for eligibility in non-dialysis, non-HFpEF patients who were able to continue GDMT treatment for more than 6 months after adding Vericiguat.

Predicting invasive disease-free survival in ER-positive, HER2-negative early breast cancer using the PAM50 risk-of-recurrence score: a retrospective analysis using single-center long-term follow-up data of postmenopausal Japanese patients.

BACKGROUND: The prognostic value of the risk-of-recurrence (ROR) score calculated using PAM50 has been validated using clinical trials and patient cohorts. This study aimed to investigate the prognostic value of the PAM50 ROR score in Japanese patients with early breast cancer using long-term follow-up data. METHODS: We enrolled postmenopausal patients with ER-positive, HER2-negative, stage I-II breast cancer who had undergone surgery at the Kyoto University Hospital between 2008 and 2014. The intrinsic subtype and ROR score were calculated using PAM50. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: We enrolled 146 patients, of whom 47 (32%) patients had node-positive disease, and 36 (25%) had received neoadjuvant or adjuvant chemotherapy. The proportions of intrinsic subtypes for luminal A, luminal B, HER2-enriched, and basal-like subtypes were 67%, 27%, 3%, and 2%, respectively. The median follow-up duration was 8.4 (range 6.3-10.0) years, and 21 IDFS events were observed. Based on the ROR score, 37%, 33%, and 30% of the patients were classified as low, intermediate, and high risks, respectively. Patients in the high-risk group had a significantly worse 8-year IDFS rate than those in the low-to-intermediate-risk groups (75.1% vs. 91.6%, p = 0.04). The same trend was observed in patients with and without neoadjuvant or adjuvant chemotherapy. CONCLUSIONS: Using long-term follow-up data, this study showed that the ROR score can predict the prognosis of ER-positive, HER2-negative early breast cancer in Japanese postmenopausal patients. Further investigations are required to confirm the prognostic value of the ROR score in Asian populations.

Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169+ macrophages by metastatic breast cancers.

BACKGROUND: Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes. METHODS: We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients). FINDINGS: The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm2, p = 0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169+ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169+ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022). INTERPRETATION: We concluded that lymph nodes with breast cancer metastases have fewer CD169+ macrophages, which may be detrimental to the activity of anti-cancer immunity. FUNDING: JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS.

Remarkable remission of symptomatic dermatomyositis after curative breast cancer surgery.

Dermatomyositis (DM) is an autoimmune disease that causes proximal muscle weakness in the extremities leading to severe immobility and dysphagia. Approximately 20% of patients with DM are positive for anti-TIF-1γ antibody and frequently accompanied by malignant tumors. Although DM remission after tumor resection has been reported, the indications for surgery in patients with severe DM are unknown. Herein, we report a case of a 79-year-old Japanese woman who presented with breast cancer and anti-TIF-1γ antibody-positive DM. She became bedridden shortly after DM onset. Although pulsed steroid therapy, intravenous immunoglobulin, tacrolimus, and endocrine therapy with fulvestrant did not improve her symptoms, tumor resection with axillary lymph node dissection resulted in complete remission of the DM after 8 months. Immunohistochemistry revealed high expression of TIF-1γ in cancer cells, both in the primary tumor and axillary lymph nodes. Since the serum levels of anti-TIF-1γ antibody decreased after the surgery, the existence of breast cancer with TIF-1γ expression may have contributed to the worsening of DM. The present case suggests that curative surgery should be considered as a treatment option even if the patient has severe symptoms, such as immobility and dysphagia. Careful discussions with patients and multidisciplinary collaboration are essential to make surgery feasible, particularly for those with severe symptomatic DM.

Image of a thawed frozen specimen obtained using a cryoprobe floated with oil droplets in normal saline: An endobronchial lipomatous hamartoma image.

Hereby, we present a rare case of a resected endobronchial tumour that floated or showed oil droplets in saline. In this study, we report an interesting image related to endobronchial lipomatous hamartoma cryotherapy.

Non-surgical ablation for breast cancer: an emerging therapeutic option.

Non-surgical ablation is emerging as an alternative local therapy option for patients with early-stage breast cancer and encompasses two main types of percutaneous therapeutic procedures: radiofrequency ablation and cryoablation. Both techniques involve obliteration of a spherical lesion and feasibility studies have shown that complete tumour ablation is achievable with good or excellent cosmetic results. Although few clinical studies have directly compared non-surgical ablation with conventional surgical resection, observational studies indicate that clinical outcomes are favourable with acceptable rates of local control and no detriment to long-term survival. There remain outstanding issues with these percutaneous ablative techniques that require resolution before they could be incorporated into routine clinical practice. Hence, a consensus meeting was convened to discuss the challenges of non-surgical ablation and clarify indications for its use alongside clinical management pathways. In this Policy Review we will address some of the broader biological aspects of non-surgical ablation, including immune-modulatory effects and potential novel applications for the future.

Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. METHODS: In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. RESULTS: We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. CONCLUSION: We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Fosfomycin as salvage therapy for persistent methicillin-resistant Staphylococcus aureus bacteremia: A case series and review of the literature.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia can be persistent and refractory; however, the optimal approach for its treatment has not been determined. Although fosfomycin (FOM) has been shown to have synergistic effects with anti-MRSA agents in vitro, clinical experience with FOM combination therapy is limited. Thus, we present cases of persistent MRSA bacteremia that improved with the addition of FOM. In case 1, a 48-year-old man with prosthetic vascular graft infection developed persistent MRSA bacteremia despite vancomycin (VCM) and daptomycin (DAP) administration. On day 46, after the first positive blood culture, we added FOM to DAP. The blood culture became negative on day 53. In case 2, an 85-year-old woman presented with pacemaker-related MRSA bacteremia. She was treated with VCM, followed by DAP and DAP plus rifampicin. However, the bacteremia persisted for 32 days because of difficulties in immediate pacemaker removal. After adding FOM to DAP, the blood culture became negative on day 38. In case 3, a 57-year-old woman developed persistent MRSA bacteremia due to pulmonary valve endocarditis and pulmonary artery thrombosis after total esophagectomy for esophageal cancer. The bacteremia continued for 50 days despite treatment with DAP, followed by VCM, VCM plus minocycline, DAP plus linezolid (LZD), and VCM plus LZD. She was managed conservatively because of surgical complications. After adding FOM to VCM on day 51, the blood culture became negative on day 58. FOM combination therapy may be effective in eliminating bacteria and can serve as salvage therapy for refractory MRSA bacteremia.

Comparison of cisplatin-based versus standard preoperative chemotherapy in patients with operable triple-negative breast cancer: propensity score matching and inverse probability of treatment weighting analysis.

PURPOSE: The efficacy of carboplatin is non-equivalent to that of cisplatin (CDDP) for various tumor types in curative settings. However, the role of CDDP in operable triple-negative breast cancer (TNBC) patients remains unknown. We conducted a multicenter observational study to examine the effects of CDDP added to preoperative chemotherapy in patients with TNBC. METHODS: This retrospective study consecutively included previously untreated patients with stage I-III TNBC treated with preoperative chemotherapy with or without CDDP. The primary endpoint was distant disease-free survival (DDFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases in comparisons between the two groups. RESULTS: A total of 138 patients were enrolled in the study. Of these, 52 were in the CDDP group and 86 in the non-CDDP group. DDFS was significantly better in the CDDP group than in the non-CDDP group (unadjusted hazard ratio (HR) 0.127 and p < 0.001, PSM HR 0.141 and p < 0.003, IPTW HR 0.123 and p = < 0.001). Furthermore, among the patients with residual cancer burden (RCB) class II/III, DDFS was better in the CDDP group than in the non-CDDP group (unadjusted HR 0.192 and p = 0.013, PSM HR 0.237 and p = 0.051, IPTW HR 0.124 and p = 0.059). CONCLUSION: Our study showed that CDDP-containing regimens achieved favorable prognoses in patients with operable TNBC, especially for the RCB class II/III population. Confirmative studies are warranted to elucidate the role of CDDP in TNBC treatment.

Ultrafast Dynamic Contrast-Enhanced MRI of the Breast: From Theory to Practice.

The development of ultrafast dynamic contrast-enhanced (UF-DCE) MRI has occurred in tandem with fast MRI scan techniques, particularly view-sharing and compressed sensing. Understanding the strengths of each technique and optimizing the relevant parameters are essential to their implementation. UF-DCE MRI has now shifted from research protocols to becoming a part of clinical scan protocols for breast cancer. UF-DCE MRI is expected to compensate for the low specificity of abbreviated MRI by adding kinetic information from the upslope of the time-intensity curve. Because kinetic information from UF-DCE MRI is obtained from the shape and timing of the initial upslope, various new kinetic parameters have been proposed. These parameters may be associated with receptor status or prognostic markers for breast cancer. In addition to the diagnosis of malignant lesions, more emphasis has been placed on predicting and evaluating treatment response because hyper-vascularity is linked to the aggressiveness of breast cancers. In clinical practice, it is important to note that breast lesion images obtained from UF-DCE MRI are slightly different from those obtained by conventional DCE MRI in terms of morphology. A major benefit of using UF-DCE MRI is avoidance of the marked or moderate background parenchymal enhancement (BPE) that can obscure the target enhancing lesions. BPE is less prominent in the earlier phases of UF-DCE MRI, which offers better lesion-to-noise contrast. The excellent contrast of early-enhancing vessels provides a key to understanding the detailed pathological structure of tumor-associated vessels. UF-DCE MRI is normally accompanied by a large volume of image data for which automated/artificial intelligence-based processing is expected to be useful. In this review, both the theoretical and practical aspects of UF-DCE MRI are summarized. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer.

PURPOSE: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups. METHODS: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated. RESULTS: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33-0.78) and 29% (HR: 0.71, 95% CI 0.49-1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29-0.74). CONCLUSIONS: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.

Evolutionary histories of breast cancer and related clones.

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1-3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient's early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

Performance of dedicated breast PET in breast cancer screening: comparison with digital mammography plus digital breast tomosynthesis and ultrasound.

OBJECTIVE: To compare the diagnostic performance of dedicated breast positron emission tomography (dbPET) in breast cancer screening with digital mammography plus digital breast tomosynthesis (DM-DBT) and breast ultrasound (US). METHODS: Women who participated in opportunistic whole-body PET/computed tomography cancer screening programs with breast examinations using dbPET, DM-DBT, and US between 2016-2020, whose results were determined pathologically or by follow-up for at least 1 year, were included. DbPET, DM-DBT, and US assessments were classified into four diagnostic categories: A (no abnormality), B (mild abnormality), C (need for follow-up), and D (recommend further examination). Category D was defined as screening positive. Each modality's recall rate, sensitivity, specificity, and positive predictive value (PPV) were calculated per examination to evaluate their diagnostic performance for breast cancer. RESULTS: Out of 2156 screenings, 18 breast cancer cases were diagnosed during the follow-up period (10 invasive cancers and eight ductal carcinomas in situ [DCIS]). The recall rates for dbPET, DM-DBT, and US were 17.8%, 19.2%, and 9.4%, respectively. The recall rate of dbPET was highest in the first year and subsequently decreased to 11.4%. dbPET, DM-DBT, and US had sensitivities of 72.2%, 88.9%, and 83.3%; specificities of 82.6%, 81.4%, and 91.2%; and PPVs of 3.4%, 3.9%, and 7.4%, respectively. The sensitivities of dbPET, DM-DBT, and US for invasive cancers were 90%, 100%, and 90%, respectively. There were no significant differences between the modalities. One case of dbPET-false-negative invasive cancer was identified in retrospect. DbPET had 50% sensitivity for DCIS, while that of both DM-DBT and US was 75%. Furthermore, the specificity of dbPET in the first year was the lowest among all periods, and modalities increased over the years to 88.7%. The specificity of dbPET was significantly higher than that of DM-DBT (p < 0.01) in the last 3 years. CONCLUSIONS: DbPET had a compatible sensitivity to DM-DBT and breast US for invasive breast cancer. The specificity of dbPET was improved and became higher than that of DM-DBT. DbPET may be a feasible screening modality.

An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9.

BACKGROUND: Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. METHODS: Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. RESULTS: Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the "master regulator" of TNBCs. CONCLUSIONS: POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs.

Patient characteristics, treatment patterns, and outcomes of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer patients prescribed cyclin-dependent kinase 4 and 6 inhibitors: large-scale data analysis using a Japanese claims database.

PURPOSE: The aim was to understand real-world cyclin-dependent kinase (CDK) 4 and 6 inhibitor use in Japan. METHODS: This retrospective observational study used a Japanese administrative claims database and included patients with presumptive hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) prescribed CDK4 and 6 inhibitor therapy between December 2017 and March 2021. Patient characteristics, treatment patterns, and selected clinical and safety outcomes were descriptively summarized. Time to discontinuation (TTD) and chemotherapy-free survival (CFS) were examined using Kaplan-Meier estimates. RESULTS: The study cohort (N = 6442) was predominantly female (99.4%; median [range] age 64 [26-99] years) with records of metastases (79.6%) within 1 year prior to initiating CDK4 and 6 inhibitor therapy. In total, 4463 (69.3%) and 1979 (30.7%) were prescribed palbociclib and abemaciclib, respectively, as their first CDK4 and 6 inhibitor, most commonly in combination with fulvestrant (n = 3801; 59.0%). Overall, 3756 patients initiated a subsequent anticancer treatment, of whom 748 (19.9%) initiated a different CDK4 and 6 inhibitor in combination with the same or different endocrine therapy. Median TTD (95% confidence interval) was 9.7 (9.3, 10.1) months for the first CDK4 and 6 inhibitor therapy. Median CFS was 26.1 (24.6, 27.8) months. Incidence of clinically relevant diarrhea was higher after abemaciclib initiation (9.8%) than after palbociclib initiation (1.5%). More patients experienced dose reduction with palbociclib (69.3%) than with abemaciclib (53.0%). CONCLUSION: The data provide insights into current clinical practices for CDK4 and 6 inhibitor use in Japan that could help establish future treatment strategies for ABC.

Unilateral Reduction of 18F-FDG Accumulation in Brown Adipose Tissue by Sympathectomy for Hyperhidrosis.

ABSTRACT: A 30-year-old woman with left breast cancer underwent 18F-FDG PET/CT for staging. Intense FDG uptake was observed in the primary lesion, as well as on the left side of the neck to the supraclavicular fossa and left paravertebral region. History taking revealed that she had undergone a right thoracic sympathectomy for hyperhidrosis, which resulted in attenuated FDG uptake in the right-sided brown adipose tissue (BAT). With another examination keeping adequate warming, the accumulation of BAT was reduced and a diagnosis of cT1N1M0 was made. Unilateral sympathetic blockade can cause asymmetric FDG accumulation in BAT, which interferes with interpretation in tumors.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes of HR+, HER2- Early Breast Cancer Patients in Japan: An Analysis with National Database(NDB).

Real-world evidence for clinical outcomes and treatment patterns in patients with hormone receptor-positive(HR+)and human epidermal growth factor receptor 2-negative(HER2-)early breast cancer(EBC)in Japan is limited. We aimed to provide recent evidence in this population using the National Database of Health Insurance Claims and Specific Health Check-ups of Japan(NDB). Adults ≥20 years old who were diagnosed with HR+/HER2- breast cancer and underwent breast resection surgery were followed up. Patient characteristics and treatment patterns were evaluated. Durations of overall post-operative endocrine therapy(ET)and luteinizing hormone-releasing hormone(LH-RH)agonist therapy, and time to metastasis/recurrence after surgery were analyzed using Kaplan-Meier method. Overall, 294,904 patients were included. Cyclophosphamide and tamoxifen were the most common peri-operative chemotherapeutic and ET drugs. Median(95% confidence interval[CI])duration of post-operative ET and LH-RH agonist therapy was 5.01(5.01-5.01)years and 2.13 (2.12-2.14)years, respectively. Five-year cumulative rate(95% CI)of any recurrence was 8.6%(8.5-8.7), visceral metastasis being the most common. Nation-wide treatment patterns were described, which were consistent with guideline recommendations for patients with HR+, HER2- EBC. Further discussion is required to delay metastasis/recurrence and improve clinical outcomes(Fig. 1: Plain language summary of the study).

Breast cancer detection using volatile compound profiles in exhaled breath via selected ion-flow tube mass spectrometry.

This study aimed to evaluate volatile compounds in exhaled breath as a non-invasive screening method to detect breast neoplasms. Exhaled breath samples were collected from patients with breast cancer (BC;n= 45) and non-breast cancer (NBC;n= 51) controls. Selected ion-flow tube mass spectrometry was used to quantify the volatile compounds. A multiple logistic regression (MLR) model was developed by combining multiple compounds to discriminate between BC and NBC samples. Amongst the 672 quantified peaks, 17 showed significant differences between BC and NBC samples (P< 0.05 corrected by false discovery rate). Pathway analysis revealed a significant difference in glycerophospholipid metabolism. The MLR model showed an area under the receiver operating characteristic curve (AUC) of 0.719 (95% confidence interval: 0.615-0.822,P< 0.0002). Cross-validation under various conditions resulted in a slight fluctuation in the AUC values, indicating the high generalizability of the MLR model. The model showed a higher BC probability for advanced-stage subjects and higher Ki67 (⩾30) for BC subjects. This study suggests the potential of volatile compounds in exhaled breath as a noninvasive screening method for BC.