Published papers

Background: Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-Administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. Patients and Methods: This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. Results: The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n=177) and abemaciclib (n=63) without propensity score matching. Adverse event incidence and severity were similar in both groups. Conclusion: The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.

Introduction: Solitary fibrous tumors (SFTs) are uncommon mesenchymal neoplasms that comprise <2 % of all soft tissue tumors. They are a diagnostically challenging group of neoplasms that can occur essentially anywhere. Molecular or genetic testing of soft tissue tumors will increasingly add to the foundation of distinctive histologic features, as accurate diagnosis is critical for appropriate treatment. Case presentation: A 28-year-old woman was referred to our hospital for a left breast mass. Ultrasonography showed an oval hypoechoic mass with partially obscured boundaries. Surgical specimens revealed spindle tumor cells surrounding the mammary ducts and were immunoreactive for both CD34 and STAT6, suggesting SFTs. However, the infiltration of spindle tumor cells into the surrounding fat, and the storiform-like pattern made us consider dermatofibrosarcoma protuberans (DFSP) as a differential diagnosis. Lack of amplification of the COL1A1-PDGFB fusion gene, a characteristic feature of DFSP, led to our definitive diagnosis of breast SFT. Discussion: The presence of STAT6 in tumor cell nuclei is a highly sensitive immunohistochemical marker for SFT. In our case, morphological features evoked the differential diagnosis of DFSP and we investigated the COL1A1-PDGFB fusion gene. The diagnostic process of reliably performing careful morphological examination and immunohistochemical marker test, and then obtain conviction by molecular cytogenetic technique is more and more important for soft tissue tumors. Conclusions: We report a quite uncommon case of breast SFT and excluded DFSP as a differential diagnosis. If it is difficult to distinguish between these diseases, molecular cytogenetic analysis would be required for accurate diagnosis.

In the medical field, surgical videos can be used to introduce surgical skills. Medical students and residents watch the videos to study the surgical skills and increase learning speed by compensating for the lack of experience in surgical rooms due to limited opportunity to join in surgery. To record egocentric surgical videos by a wearable camera is a solution to record surgical skills of a surgeon in detail. However, most egocentric surgical videos are of quite long duration. For example, in the case of tumor removal in breast surgery, a video recording time often reaches 2h. With that length, it is time consuming to see important scenes in the video, particularly because many surgical videos include nonessential scenes such as sterilization and preparation of tools. For extracting specific scenes from a long video, we can apply scene estimation by machine learning. Furthermore, it is important to know where the surgeon is looking to observe the area of the incision in detail. In particular, it is vital to be able to zoom in on key elements, allowing viewers to see the incision area and the fine details of the necessary surgical skills. In this study, we aimed to highlight incision scenes from egocentric surgical videos in the spatiotemporal domain by utilizing two neural networks for the temporal and spatial highlights. For the temporal highlights, we designed a neural network that estimates the incision scenes by learning gaze speed, hand movements, number of hands, and background movements in egocentric surgical videos. For the spatial highlights, in order to estimate the important area to zoom in, we designed a neural network that learns the surgeon's gaze on natural features of surgical scenes to form a probability map as a representation of the estimated gaze area. The estimated gaze area was also used to calculate the appropriate zoom-in position and zoom-in ratio. To control the highlighted parameters in accord with user preferences, we also made a user interface that allows for the selection of playback speed gain and zoom ratio gain. For the evaluation, we verified the performance of the networks by a quantitative assessment and conducted a user study with medical doctors by showing an actual surgical video to obtain a qualitative assessment on the proposed system.

In Japan, mammography is commonly used for breast cancer screening. However, the mortality rate has not decreased, possibly due to the low screening uptake and the high prevalence of dense breast tissue among Japanese women, which reduces mammography's effectiveness. A recent prospective study in Japan, J-START, demonstrated that combining mammography with ultrasonography increases detection rates and reduces the incidence of interval cancers, highlighting the significance of ultrasound examinations.Artificial Intelligence (AI) technologies, particularly in machine learning and deep learning, offer promising solutions to enhance the accuracy and efficiency of breast ultrasound diagnostics. This review explores AI's current capabilities in breast ultrasound imaging, emphasizing key advancements in breast lesion detection and diagnosis. Additionally, we introduce AI-based breast ultrasound diagnostic support programs approved by the Pharmaceuticals and Medical Devices Agency, which include programs for detecting lesion candidate regions and diagnosing the necessity of further examination based on detected lesion candidates. These AI tools are expected to improve diagnostic accuracy and efficiency.While AI holds significant promise, several challenges remain. It is essential for physicians to oversee its use responsibly, as there are concerns regarding patient acceptance and environmental impact. This review underscores the revolutionary potential of AI in breast cancer diagnostics and emphasizes the importance of ongoing research and development to overcome existing limitations.

Objective: This study examined the relationship between symptom burdens and work-related outcomes, including work participation and overall work impairment (OWI) among breast cancer survivors (BCS) receiving adjuvant endocrine therapy (AET). Methods: This was a cross-sectional study with 140 BCS of working age receiving AET. Data were collected using self-report questionnaires that included an assessment of symptoms and their employment status, and OWI. Data were analyzed using descriptive statistics and multiple logistic regression analysis. Results: A total of 111 (79%) survivors reported being employed at the time of the survey. Symptom burdens were not associated with unemployment. Of the 110 working BCS receiving AET, symptom burdens were significantly related to a higher degree of OWI (OR ​= ​2.14, 95% CI, 1.58–2.89, P ​≤ ​0.001). Conclusions: Participating BCS receiving AET continued to work while experiencing symptoms, with survivors who experienced high symptom burdens being negatively affected in their work life. Healthcare providers need to assess and manage symptoms and their impact on work, with the help of employers, to improve the quality of work life of BCS receiving AET.

The purpose of this study was to gain insights into the relationship between chemotherapy-induced peripheral neuropathy (CIPN), physical activity, and health-related quality of life (HRQOL) in breast cancer patients who received taxane-based chemotherapy. We conducted a cross-sectional, observational study on 43 breast cancer patients who underwent taxane-based chemotherapy. Information on demographics, CIPN (Ntx subscale), HRQOL (FACT-G), physical activity (IPAQ-SF), and psychological distress (K6) was collected through self-administered questionnaires. Data of clinical characteristics were extracted from the patients' medical records. Correlation analysis revealed a significant positive correlation between CIPN and HRQOL (r = 0.55, p < 0.001), physical well-being (r = 0.72, p < 0.001), emotional well-being (r = 0.41, p < 0.01), and functional well-being (r = 0.47, p < 0.01) but not physical activity. There was no significant correlation between physical activity and HRQOL. Among the 19 patients with severe symptoms of CIPN, an analysis of physical activity showed that 7 (36.8%) were inactive and 12 (63.2%) were active. Hence, CIPN significantly affects the HRQOL of breast cancer patients. Additionally, some patients perform physical activity according to their individual roles and environment by managing and enduring the symptoms of CIPN. Nurses should recognize the impact of CIPN on patients’ everyday lives, adequately assess the CIPN symptoms, evaluate the influence of CIPN on patients’ physical activity levels, and counsel patients accordingly. Additionally it is necessary to consider patients individually how to perform physical activity safely, especially when experiencing CIPN.

In breast cancer screening, AI-based computer-aided diagnosis (AI-CAD) software has been introduced into diagnostic imaging, mainly mammography (MG), with the expectation of improving sensitivity or efficiency in reading. Overseas evidence demonstrates that sensitivity and specificity of AI-CAD in diagnosing breast cancer is equivalent to those of human readers. Reducing the work load of screening by replacing one of the readers by AI-CAD has been attempted. On the other hand, pitfalls of AI-CAD include automation bias, and the fluctuation of performance by AI-CAD caused by biased training data. Furthermore, when incorporating AI into actual clinical practice, operational considerations—such as the specific conditions of each facility, feasibility of system implementation and cloud utilization, security measures, and determining who will reference the AI-CAD output and at what stage—must all be taken into account. In the midst of the transition, it is becoming indispensable to develop guidelines at the academic society level, establish quality assurance systems, and accumulate evidence to verify AI’s usefulness over the mid to long term.

Copyright © Spandidos Publications 2017. All rights reserved. The human epidermal growth factor receptor 2 (HER2)-targeting agent, lapatinib, combined with oral fluoropyrimidine capecitabine, has been previously demonstrated to be an effective treatment option for patients with trastuzumab-resistant HER2-positive metastatic breast cancer. To investigate the molecular mechanisms associated with the interactions between lapatinib and capecitabine, the effect of treatment with lapatinib and phosphatidylinositol-4,5-bispho-sphate 3-kinase (PI3K) inhibitors on the expression of E2F transcription factor 1 (E2F1) and thymidylate synthase (TS), which is associated with an increased response to 5-fluorouracil (5-FU)-based chemotherapy, was determined in HER2-positive breast cancer cells. The results of reverse transcription-quantitative polymerase chain reaction demonstrated that administration of lapatinib and PI3K inhibitors decreased the mRNA expression of TS and E2F1, a transcription factor that promotes TS gene expression, in SKBR3 and T47D cell lines. Furthermore, treatment with lapatinib and PI3K inhibitors also suppressed the mRNA expression of ribonucleotide reductase M1 subunit (RRM1), an important determinant of gemcitabine resistance, and DNA topoisomerase II-? (TOP2A), a molecular target of anthracyclines, in SKBR3 and T47D cell lines. Western blot analysis further demonstrated that the phosphorylation of Akt was inhibited by lapatinib, and the results of the MTT assay revealed that the combination of lapatinib with either 5-FU or gemcitabine demonstrated synergistic antitumor effects, whereas a combinatory treatment of lapatinib with epirubicin, a typical anthracycline drug, exhibited antagonistic antitumor effects in HER2-positive breast cancer cells. These results indicate that the synergistic antitumor effects exhibited by combinatory treatment of lapatinib with capecitabine may be induced via the suppression of E2F1-mediated TS expression.

© 2018 Wiley Periodicals, Inc. The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P <.001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P <.001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P =.0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

© AlphaMed Press 2018 Background: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. Methods: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. Results: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56–1.97, and OR, 2.25; 95% CrI, 1.66–3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. Conclusion: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. Implications for Practice: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.