Information regarding patients who were treated for breast cancer in 2018 was extracted from the National Clinical Database (NCD), which is run by Japanese physicians. This database continues from ...1975, created by the Japanese Breast Cancer Society (JBCS). A total of 95,620 breast cancer cases were registered. The demographics, clinical characteristics, pathology, surgical treatment, adjuvant chemotherapy, adjuvant endocrine therapy, and radiation therapy of Japanese breast cancer patients were summarized. We made comparisons with other reports to reveal the characteristics of our database. We also described some features in Japanese breast cancer that changed over time. The unique characteristics of breast cancer patients in Japan may provide guidance for future research and improvement in healthcare services.
Although the categorization of ultrasound using the Breast Imaging Reporting and Data System (BI‐RADS) has become widespread worldwide, the problem of inter‐observer variability remains. To maintain ...uniformity in diagnostic accuracy, we have developed a system in which artificial intelligence (AI) can distinguish whether a static image obtained using a breast ultrasound represents BI‐RADS3 or lower or BI‐RADS4a or higher to determine the medical management that should be performed on a patient whose breast ultrasound shows abnormalities. To establish and validate the AI system, a training dataset consisting of 4028 images containing 5014 lesions and a test dataset consisting of 3166 images containing 3656 lesions were collected and annotated. We selected a setting that maximized the area under the curve (AUC) and minimized the difference in sensitivity and specificity by adjusting the internal parameters of the AI system, achieving an AUC, sensitivity, and specificity of 0.95, 91.2%, and 90.7%, respectively. Furthermore, based on 30 images extracted from the test data, the diagnostic accuracy of 20 clinicians and the AI system was compared, and the AI system was found to be significantly superior to the clinicians (McNemar test, p < 0.001). Although deep‐learning methods to categorize benign and malignant tumors using breast ultrasound have been extensively reported, our work represents the first attempt to establish an AI system to classify BI‐RADS3 or lower and BI‐RADS4a or higher successfully, providing important implications for clinical actions. These results suggest that the AI diagnostic system is sufficient to proceed to the next stage of clinical application.
ROC curve by possible thresholds of the confidence score for the detection in each image of BI‐RADS 4A or higher.
Background
The Japanese Breast Cancer Society Registry started in 1975; it was transferred to the registry platform of the National Clinical Database in 2012. We provide the annual data and an ...analysis of the Breast Cancer Registry for 2017.
Methods
Patients’ characteristics and pathological data of the 95,203 registered Japanese breast cancer patients from 1,427 institutes in 2017 were obtained. Trends in age at diagnosis and pathological stage were determined during the most recent 6 years (2012–2017).
Results
The mean onset age was 60.2 years with bimodal peaks at 45–49 years and 65–69 years. A short-term trend of the most recent 6 years of data caused the second, older peak. At diagnosis, 32.4% of breast cancer patients were premenopausal. The distribution of stages revealed that the proportion of early stage breast cancer (stage 0–I) increased up to 60%. At the initial diagnosis, 2.2% of patients presented with metastatic disease. Sentinel node biopsy without axillary node dissection was performed without neoadjuvant chemotherapy (NAC) in 68.8%, and with NAC in 31.1%, of patients. For patients without NAC, lymph node metastasis was less than 3% if the tumor size was less than 1 cm. The proportion of node-negativity decreased to 79.5% when tumor size was 2.1–5 cm.
Conclusions
This analysis of the registry provides new information for effective treatment in clinical practice, cancer prevention, and the conduct of clinical trials. Further development of the registry and progress in collecting prognostic data will greatly enhance its scientific value.
Summary Background Oral fluoropyrimidines are used for the first-line treatment of metastatic breast cancer to avoid severe adverse effects, although firm supporting evidence is lacking. We aimed to ...establish whether S-1 is non-inferior to taxanes in this setting. Methods We did an open-label, non-inferiority, phase 3 trial at 154 hospitals in Japan. We enrolled individuals who had HER2-negative metastatic breast cancer who had received no chemotherapy for advanced disease, and who were resistant to endocrine treatment. Patients were randomly assigned (1:1) either to taxane (docetaxel 60–75 mg/m2 at intervals of 3–4 weeks; paclitaxel 80–100 mg/m2 weekly for 3 of 4 weeks; or paclitaxel 175 mg/m2 at intervals of 3–4 weeks) or to S-1 (40–60 mg twice daily for 28 consecutive days, followed by a 14-day break). Randomisation was done centrally with the minimisation method, with stratification by institution, liver metastasis, oestrogen and progesterone receptor status, previous treatment with taxanes or oral fluorouracil, and time from surgery to recurrence. The primary endpoint was overall survival, with a prespecified non-inferiority margin of 1·333 for the hazard ratio (HR). The primary efficacy analysis was done in the full analysis set, which consisted of all patients who took at least one study treatment and who had all data after randomisation. This trial is registered with the University Hospital Medical Information Network, Japan (protocol ID C000000416). Findings Between Oct 27, 2006, and July 30, 2010, we enrolled 618 patients (309 assigned to taxane; 309 assigned to S-1). The full analysis set consisted of 286 patients in the taxane group and 306 in the S-1 group. Median follow-up was 34·6 months (IQR 17·9–44·4). Median overall survival was 35·0 months (95% CI 31·1–39·0) in the S-1 group and 37·2 months (33·0–40·1) in the taxane group (HR 1·05 95% CI 0·86–1·27; pnon-inferiority =0·015). The most common grade 3 or worse adverse events were neutropenia (20 7% of 307 patients in the S-1 group vs nine 3% of 290 patients in the taxane group), fatigue (ten 3% vs 12 4%), and oedema (one <1% vs 12 4%). Treatment-related deaths were reported in two patients in the taxane group. Interpretation S-1 is non-inferior to taxane with respect to overall survival as a first-line treatment for metastatic breast cancer. S-1 should be considered a new option for first-line chemotherapy for patients with HER2-negative metastatic breast cancer. Funding Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan; Taiho.
Background
Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US ...residents with Japanese origin (USJ), and US residents with other origins (USO).
Method
Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan–Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status.
Results
We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval CI 0.45–0.47 for Japanese and 0.66 95% CI 0.59–0.74 for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 95% CI 0.51–0.55 for Japanese and 0.53 95% CI 0.52–0.74 for USJ).
Conclusions
In stage I–III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.
The Japanese Breast Cancer Society (JBCS) registry began data collection in 1975, and it was integrated into National Clinical Database in 2012. As of 2016, the JBCS registry contains records of ...656,896 breast cancer patients from more than 1400 hospitals throughout Japan. In the 2016 registration, the number of institutes involved was 1422, and the total number of patients was 95,870. We herein present the summary of the annual data of the JBCS registry collected in 2016. We analyzed the demographic and clinicopathologic characteristics of registered breast cancer patients from various angles. Especially, we examined the registrations on family history, menstruation, onset age, body mass index according to age, nodal status based on tumor size and subtype, and proportion based on ER, PgR, and HER2 status. This report based on the JBCS registry would support clinical management for breast cancer patients and clinical study in the near future.
Background
Sentinel lymph node biopsy is widely applied for the management of clinically node-negative breast cancer, and a radioisotope with a blue dye are most often used as tracers. Fluorescence ...of indocyanine green could also potentially be used as tracer. This study aimed to demonstrate the long-term survival results of fluorescence-guided sentinel lymph node biopsy.
Patients and methods
Patients with clinically node-negative breast cancer who underwent surgery as initial treatment were included in this study. Both fluorescence of indocyanine green and indigo carmine blue dye were used as tracers. Axillary lymph node dissection was omitted unless metastasis was pathologically proven in sentinel nodes. Breast cancer recurrence and death were recorded and prognostic factors were identified using disease-free survival and overall survival data.
Results
A total of 565 patients were analyzed. There were 14 (2.5%) patients whose sentinel nodes could not be identified, yielding an identification rate of 97.5%. Axillary dissection was performed in 90 patients. Forty-three recurrences including 6 ipsilateral axilla recurrence and 13 deaths were observed during the median 83 months of follow-up period. Seven-year disease-free and overall survival were 92.4% and 97.3%, respectively. Multivariate analyses demonstrated that pre-menopausal status and invasive lobular carcinoma were significant unfavorable prognostic factors of disease-free survival. Half of ipsilateral axilla recurrences occurred within 5 years after surgery and these recurrences were correlated with inappropriate adjuvant therapy.
Conclusion
Fluorescence-guided sentinel lymph node biopsy demonstrated favorable prognostic results and could be alternative to the radioisotope for clinically node-negative breast cancer.
The effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumour expression after initial therapy, relative to that of standard chemotherapy, has not been evaluated.
...Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumour biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab were continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Ki-67 early responder is defined as the absolute Ki-67 value that was <10%, and the percentage of Ki-67-positive tumour cells was reduced by >30% compared with before treatment. Early Ki-67 responders continued to receive the same treatment, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate.
A total of 237 patients were randomised. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm was inferior to that in the control arm (44.1%; 31.4-56.7; P = 0.025).
The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer.
Clinical Trial Registration: UMIN-CTR as UMIN000007074.
Endocrine therapy is an essential component in the curative treatment of hormone receptor (HR)-positive breast cancer. To improve treatment efficacy, the addition of metronomic chemotherapy has been ...tested and shown to improve therapeutic effects. To better understand cellular reactions to metronomic chemoendocrine therapy, we studied autophagy-related markers, beclin 1 and LC3, and apoptosis-related markers, TUNEL and M30, in pre- and post-treatment cancer tissues from a multicenter neoadjuvant trial, JBCRG-07, in which oral cyclophosphamide plus letrozole were administered to postmenopausal patients with HR-positive breast cancer. Changes in the levels of markers were compared with those following neoadjuvant endocrine therapy according to clinical response. Apoptosis, in addition to autophagy-related markers, increased following metronomic chemoendocrine therapy and such increases were associated with clinical response. By contrast, following endocrine therapy, the levels of apoptosis-related markers did not increase regardless of clinical response, whereas the levels of autophagy-related markers increased. Furthermore, levels of the apoptosis-related marker, M30, decreased in responders of endocrine therapy, suggesting that the induction of apoptosis by metronomic chemoendocrine therapy was involved in the improved clinical outcome compared with endocrine therapy. In conclusion, metronomic chemoendocrine therapy induced a different cellular reaction from that of endocrine therapy, including the induction of apoptosis, which is likely to contribute to improved efficacy compared with endocrine therapy alone.
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