An Improvement of Exertional Dyspnea by the Reintroduction of Anti-EGFR Antibody in Patients with Metastatic Rectal Cancer Who Developed Cancerous Lymphangiopathy: A Case Report.

Introduction: Reexposure to anti-EGFR antibodies, such as a reintroduction or rechallenge with anti-EGFR antibodies, has attracted much attention in the field of metastatic colorectal cancer. A reintroduction of anti-EGFR antibodies often shows good therapeutic outcomes, as most patients eligible for such reintroduction discontinued treatment due to adverse events despite a good treatment response during front-line treatment. We herein report a case demonstrating an improvement in exertional dyspnea after the reintroduction of anti-EGFR antibody in a patient with metastatic rectal cancer who developed cancerous lymphangiopathy. Case Presentation: A 68-year-old man who had undergone curative surgery for stage IIIB rectal cancer was diagnosed with multiple lung metastases. During the late-line treatment, respiratory failure developed because of multiple lung metastases and cancerous lymphangiopathy. Two months after the initiation of irinotecan + cetuximab, which had been discontinued due to acneiform eruptions despite a good treatment response as a first-line treatment, his dyspnea and performance status dramatically improved. Conclusion: This case indicates that the reintroduction of anti-EGFR antibody to patients who have discontinued anti-EGFR antibody due to skin toxicity despite a good treatment response is a very useful treatment option for metastatic colorectal cancer.

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.

Impact of Preoperative Nutritional Status on Long-term Survival in Patients With Stage I-III Colorectal Cancer.

BACKGROUND/AIM: In addition to oncological and treatment factors, the outcomes of cancer treatment are greatly influenced by host factors, such as the nutritional status. The aim of this study was to evaluate the association between the preoperative nutritional status and the prognosis of colorectal cancer patients using three nutritional indices. PATIENTS AND METHODS: The target cohort consisted of 529 patients with stage I-III colorectal cancer, who underwent curative surgery between January 2015 and December 2019. The nutritional indices were calculated according to the equations that follow. Prognostic nutritional index (PNI)=10×serum albumin concentration (g/dl) +0.005×peripheral lymphocyte count (/µl). Nutritional risk index (NRI)=15.19×serum albumin concentration (g/dl)+41.7×present weight/usual weight. Geriatric nutritional risk index (GNRI)=14.89×serum albumin concentration (g/dl)+41.7×present weight/ideal weight. Ideal weight was calculated as follows: height(cm)-100-[(height(cm)-150)/4] for men and height(cm)-100-[(height(cm)-150)/2.5] for women. RESULTS: In common with all nutritional indices (PNI, NRI and GNRI), the low-nutritional index group had significantly lower relapse-free and overall survival rates than the high-nutritional index group. Furthermore, a subgroup analysis according to the NRI showed the association of the NRI with the patient prognosis for each stage. CONCLUSION: The preoperative nutritional status may have a close relationship with the prognosis in patients who receive curative surgery for colorectal cancer.

Significance of the Prognostic Immune and Nutritional Index in Patients With Stage I-III Colorectal Cancer.

BACKGROUND/AIM: Recently, the prognostic immune and nutritional index (PINI), which is calculated from the peripheral monocyte count and serum albumin level, has been reported to be useful as a prognostic marker in Korean and Chinese patients with colorectal cancer. The present study therefore examined the usefulness of the PINI as a marker for predicting the prognosis in Japanese colorectal cancer patients. PATIENTS AND METHODS: A total of 529 patients who underwent curative surgery for stage I-III colorectal cancer between January 2015 and December 2019 were enrolled in this study. The PINI was calculated as [serum albumin concentration (g/dl)×0.9]-[peripheral monocyte count (mm3)×0.0007]. RESULTS: The median PINI was 3.242 (range=1.250-4.091). A receiver operating characteristic curve analysis revealed that the appropriate cut-off value of the PINI was 3.047. The low-PINI group had significantly lower relapse-free and overall survival rates than the high-PINI group (p<0.0001, p<0.0001, respectively). CONCLUSION: The PINI based on host factors is useful as a prognostic marker for Japanese patients with stage I-III colorectal cancer.

Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer.

PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). CONCLUSION: In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

[The Long Term Result of Rhomboid Flap Reconstruction for Locally Advanced Breast Cancer].

In patients undergoing mastectomy for locally advanced breast cancer, surgical skin flap reconstruction is sometimes required in order to cover large skin defects. Generally, we reconstruct by using latissimus dorsi or rectus abdominis when the direct closure is difficult. These constructions are difficult and have various complications. Our facility started rhomboid flap reconstruction after mastectomy. We report the result of rhomboid flap reconstruction. Five patients were performed rhomboid flap reconstruction. Three of 5 patients were cutaneous invasion, 1 patient was skin metastasis after mastectomy, and the other patient was Paget's disease. Regarding post operative complications, there were 2 cases of surgical site infection, 2 cases of skin necrosis and 1 case of seroma. The median length of postoperative hospital stay was 9 days. Median follow-up period was 381 days(221-508 days). Only 1 patient progressed. The median progression-free survival was 332 days(221-508 days). Rhomboid flap reconstruction is effective way for the improvement of the QOL of the patients with advanced breast cancer because the long term result was not bad and we can repair large skin defect easily.

Prognostic Role of Preoperative D-dimer Levels in Patients With Stage I-III Colorectal Cancer.

BACKGROUND/AIM: As D-dimer levels have been reported to reflect cancer activity, preoperative D-dimer levels may serve as a prognostic marker in patients with colorectal cancer. The aim of this study was to evaluate the prognostic significance of preoperative D-dimer levels in patients with stage I-III colorectal cancer who underwent curative surgery. PATIENTS AND METHODS: A total of 264 patients who underwent curative surgery for stage I-III colorectal cancer between January 2015 and December 2019 were enrolled in this study. RESULTS: The median preoperative D-dimer level was 0.8 µg/ml (range=0.4-42.5 µg/ml). Based on the results of a receiver operating characteristic curve analysis, we set 1.45 as the cut-off value and classified patients into the low (n=215) and high D-dimer (n=49) groups. The high D-dimer group had significantly lower relapse-free and overall survival in comparison to the low D-dimer group (p<0.0001, p<0.0001, respectively). CONCLUSION: Preoperative D-dimer levels can serve as a prognostic marker for stage I-III colorectal cancer.

The Significance of the D-Dimer Level as a Prognostic Marker for Survival and Treatment Outcomes in Patients With Stage IV Colorectal Cancer.

BACKGROUND/AIM: Predictive markers for survival and therapeutic efficacy in stage IV colorectal cancer have not been established. As described in our previous report, D-dimer levels may have potential utility as an indicator of cancer activity. The present study evaluated the significance of the D-dimer level as a marker for the survival and treatment outcomes in patients with stage IV colorectal cancer. PATIENTS AND METHODS: A total of 34 patients who underwent surgery for stage IV colorectal cancer between February 2017 and October 2019 were enrolled. The D-dimer level was measured using a blood sample obtained at the first visit to our hospital. RESULTS: The median preoperative D-dimer level was 1.2 µg/ml (range=0.5-41.0 µg/ml). We divided patients into two groups using a D-dimer level of 2.0 µg/ml as the cut-off value based on receiver operating characteristic curve analysis. The group with a high-D-dimer-level had a significantly shorter overall survival than that with a low D-dimer level. Progression-free survival after first-line chemotherapy tended to be better in those with a low D-dimer level group than in the high-D-dimer-level group. CONCLUSION: The preoperative D-dimer level may be a useful indicator for survival and chemotherapeutic outcome in patients with stage IV colorectal cancer.

Clinical verification of the relationship between serum lipid metabolism and immune activity in breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Lipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear. METHODS: We examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively. RESULTS: Serum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test). CONCLUSIONS: Good systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

Eribulin Treatment Promotes Re-expression of Estrogen Receptor in Endocrine Therapy-resistant Hormone Receptor-positive Breast Cancer Cells.

BACKGROUND/AIM: Hypoxia is significantly associated with the development of drug resistance, and endocrine therapy is ineffective against hormone receptor (HR)-positive breast cancer in hypoxic tumor environments. Eribulin has a unique anticancer effect in breast cancer cells and improves tumor hypoxia by vascular remodeling. Therefore, we investigated the effect of eribulin on HR-positive breast cancer cells that were resistant to endocrine blockade. MATERIALS AND METHODS: We established hypoxia-resistant breast cancer cell lines by continuous culture in a hypoxic environment. Parental and hypoxia-resistant cell lines were treated with eribulin and/or tamoxifen, and estrogen receptor (ER)-, epithelial-mesenchymal transition-, and hypoxia-related gene and protein expression changes in each surviving cell line were assessed. In addition, proliferation was assessed after eribulin treatment in the parental and hypoxia-resistant cell lines. We also assessed the effect of eribulin in vivo using subcutaneous xenograft models. RESULTS: Hypoxia-resistant cell lines showed significantly decreased expression of epithelial and ER-related markers and exhibited a higher level of resistance to tamoxifen. Conversely, eribulin treatment increased epithelial and ER-related gene and protein expression in hypoxia-resistant cell lines and enhanced the anticancer effect of tamoxifen. In in vivo xenograft models, eribulin treatment of hypoxia- and tamoxifen-resistant tumors slightly induced the re-expression of ER. In addition, hypoxia-resistant tumors treated with eribulin tended to respond better to tamoxifen. CONCLUSION: Eribulin ameliorated the aggressive behavior caused by hypoxia and induced the re-expression of ER in hypoxia-resistant breast cancer cells. Eribulin treatment of HR-positive breast cancer may resensitize cells to hormone blockade.

Prognostic Impact of Smoking on Bevacizumab Combination Chemotherapy for Advanced Breast Cancer.

BACKGROUND/AIM: Smoking has been a proven carcinogenic risk factor for various cancers, including breast cancer. Furthermore, smoking has been recognized as a prognostic factor of breast cancer. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) used in combination with chemotherapy to treat breast cancer. We, herein, investigated the effect of smoking on the prognosis of unresectable breast cancer patients who received bevacizumab plus weekly paclitaxel. PATIENTS AND METHODS: From April 2011 to June 2022, 131 patients received bevacizumab plus weekly paclitaxel for unresectable breast cancer. At their first visit to our hospital, smoking status (i.e., period of smoking and amount of smoking per day) was evaluated by interview, and packs-years were calculated. RESULTS: Time to treatment failure (TTF) was significantly longer in the high packs-years group than the low packs-years group (p=0.010, log-rank). The log-rank test showed that the high packs-years group had a significantly longer overall survival than the low packs-years group (p=0.049, log-rank). Multivariate analysis of TTF revealed that progesterone receptor (p=0.005, HR=0.408) and packs-years (p=0.007, HR=0.391) were independent factors. CONCLUSION: A history of smoking may impact prognosis of combination chemotherapy with bevacizumab for advanced breast cancer treatment.

Factor Analysis of Intraoperative Bleeding Loss and its Impact on Prognosis in Breast Cancer.

BACKGROUND/AIM: Intraoperative blood loss (IBL) during the surgical treatment of various cancers affects complication rates and prognosis. However, few studies have examined the importance of minimal IBL in breast cancer surgery. We used factor analysis to examine the prognostic importance of IBL in breast cancer. PATIENTS AND METHODS: One hundred ninety-seven patients who underwent mastectomy plus axillary lymph node dissection (level II) after preoperative chemotherapy between June 2007 and June 2021 were included. Pearson's Chi-square test was used to confirm the relationships between different factors. Kaplan-Meier survival curves and the log-rank test were used to examine prognosis. Logistic regression was performed using a Cox proportional hazards model. RESULTS: The median IBL was 55.0 g (range=5.0-420.0 g). IBL was <100 g in 143 patients (72.5%), 100-200 g in 39 patients (19.8%), and >200 g in 15 patients (7.6%). Logistic regression analysis showed that patients with IBL ≥200 g had a significantly worse prognosis (disease-free survival: p=0.003, log-rank test; overall survival: p<0.001, log-rank test). Factor analysis revealed that HER2-negative status (p=0.015), non-pathological complete response (p=0.031), obesity (p=0.001), heavy smoking (p=0.047), and diabetes mellitus (p=0.004) were significantly associated with increased IBL. CONCLUSION: IBL in breast cancer was correlated with various clinicopathological factors associated with a poor prognosis, suggesting that increased IBL may be associated with poor prognosis in breast cancer as well.

Clinical Verification on the Predictors for Febrile Neutropenia in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. In this study, we evaluated the predictors for FN according to neoadjuvant chemotherapy (NAC) in all breast cancer subtypes. PATIENTS AND METHODS: We examined 327 patients with breast cancer treated with NAC. The correlation between the development of FN and clinicopathological features, including systemic inflammatory markers, and prognosis was evaluated retrospectively. RESULTS: There were no significant differences between patients with and without FN in terms of disease-free survival or overall survival (p=0.562, p=0.149, log-rank, respectively). Low body mass index (BMI) (p<0.001), white blood cells (WBC) at baseline (p=0.008), and NAC regimen (p=0.026) significantly related with FN in all patients with breast cancer. Moreover, among patients with hormone receptor-positive/human epidermal growth factor receptor 2-positive breast cancer, low WBC (p=0.007) and low absolute lymphocyte counts (ALC) at baseline (p=0.039) were significantly associated with FN, and overall survival was significantly worse in patients with FN development (p=0.039, log-rank). CONCLUSION: Poor immune activity-related factors, low ALC or BMI, may be useful to predict the development of FN in patients with breast cancer.

[Two Cases of Advanced Recurrent Breast Cancer with Severe Heart Failure Caused By Anthracycline].

Case 1: A 48-year-old woman, had right breast cancer with multiple liver metastases. Seven courses of paclitaxel plus bevacizumab were administered, but due to disease progression, 12 courses of FEC 75(total epirubicin 900 mg/m2)were administered. 2 months after the last FEC administration, the patient developed heart failure and died about 3 months later. Case 2: A 58-year-old woman, was on endocrine therapy after surgery for left breast cancer. Recurrence of lung and bone metastases were appeared 5 years after surgery, 10 courses of FEC 75(total epirubicin 750 mg/m2)were administered due to disease progression. Eight months after the last administration of FEC, the patient developed heart failure and died about 8 months later. Anthracycline induced cardiotoxicity is irreversible and has a severe course. Therefore, anthracycline should be administered with caution.

The Cyclin-Dependent Kinase 4/6 Inhibitor Abemaciclib Is Tolerated Better than Palbociclib by Advanced Breast Cancer Patients with High Serum Albumin Levels.

The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p = 0.007; abemaciclib: p = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.

Validation of the Optimum Timing of Assessment of Tumor Infiltrating Lymphocytes During Preoperative Chemotherapy for Breast Cancer.

BACKGROUND/AIM: Tumor microenvironment (TME) assessment is considered to play an important role in the prediction of prognosis and therapeutic response following breast cancer treatment. No consensus has been reached regarding evaluation methods despite reports on the utilization of tumor-infiltrating lymphocytes (TILs) for immune TME (iTME) monitoring. Optimum timing of iTME assessment has not yet been established. PATIENTS AND METHODS: Two hundred thirty-nine patients were treated with neoadjuvant chemotherapy (NAC). During the period from diagnostic needle biopsy to NAC initiation for breast cancer, the optimal evaluation timing was examined using a receiver operating characteristic (ROC) curve analysis. RESULTS: A significant correlation between TILs and pathological complete response (pCR) was only observed in the short-term group (≤35 days) (p=0.033). Prognostic analysis revealed that in the short-term group, patients with high TIL levels had a significantly better survival prognosis relative to those with low TIL levels (>35 days) [disease-free survival (DFS): p=0.001, overall survival (OS): p=0.021]. TILs were identified as an independent factor affecting DFS in a multivariate analysis (p=0.008, hazard ratio=0.130). CONCLUSION: TIL assessment during NAC for breast cancer is a prognostic predictor only when performed at ≤35 days before NAC initiation.

The Effect of Smoking on Endocrine Therapy for Stage IV Hormone Receptor Positive Breast Cancer.

BACKGROUND/AIM: Smoking worsens breast cancer prognosis. It has been reported that tobacco components directly reach the mammary gland tissue, causing smoking-related DNA damage and biological effects. We hypothesized that smoking may have characteristics that affect the therapeutic effect and clinical course in patients with stage IV hormone receptor-positive breast cancer (HRBC) who received endocrine therapy as the first-line treatment. PATIENTS AND METHODS: Fifty-six patients diagnosed with stage IV HRBC were treated with endocrine therapy as the first-line treatment. Before treatment, the period and amount of smoking were confirmed through patient interviews, and each pack-year was recorded. RESULTS: Disease progression with new metastases was more frequent in smokers than non-smokers during endocrine therapy as first-line treatment (p=0.034). Furthermore, as the pack-year increased, new metastases tended to appear [pack-year ≤15; hazard ratio (HR)=1.929, p=0.507; pack-year 15-30, HR=3.857, p=0.223; pack-year >30, HR=7.714, p=0.028]. CONCLUSION: In stage IV HRBC, smoking increases the metastatic potential of breast cancer, suggesting that changes in its biology may lead to poor prognosis.

Optical See-through Head-mounted Display (OST-HMD)-assisted Needle Biopsy for Breast Tumor: A Technical Innovation.

BACKGROUND/AIM: Augmented reality (AR) is a new technology that provides new awareness by using a computer to extend the real environment perceived by humans. Optical see-through head-mounted displays (OST-HMD) are worn on the head and can faithfully generate an AR image by wearing the device on the head as a spectacle-type device. We developed an ultrasound-guided needle biopsy technique using OST-HMD for breast tumors. PATIENTS AND METHODS: Moverio BT-35E (Seiko Epson Corp, Nagano, Japan) was used as the OST-HMD device. This technique involves performing needle biopsy under direct vision via the gap at the bottom of the display while the ultrasound images are projected on the display of the OST-HMD worn on the head. RESULTS: With this technique, needle biopsy can be executed smoothly with no posture restrictions. A flip shade affixed to the OST-HMD has 2% transmittance, which enables clearer projection of the images. CONCLUSION: This article outlines the ultrasound-guided needle biopsy using OST-HMD. We established a safe and accurate biopsy technique with technological innovations using AR.

Severe pancytopenia caused by trifluridine/tipiracil in patients with metastatic colorectal cancer and an impaired renal function: A case report.

Although the incidence of hematological toxicity due to Trifluridine/tipiracil (FTD/TPI) treatment is high, the incidence of severe adverse events has been reported to be relatively low. However, it should be noted that patients with renal impairment are prone to severe hematological adverse events.

Development and validation of a deep learning model for detection of breast cancers in mammography from multi-institutional datasets.

OBJECTIVES: The objective of this study was to develop and validate a state-of-the-art, deep learning (DL)-based model for detecting breast cancers on mammography. METHODS: Mammograms in a hospital development dataset, a hospital test dataset, and a clinic test dataset were retrospectively collected from January 2006 through December 2017 in Osaka City University Hospital and Medcity21 Clinic. The hospital development dataset and a publicly available digital database for screening mammography (DDSM) dataset were used to train and to validate the RetinaNet, one type of DL-based model, with five-fold cross-validation. The model's sensitivity and mean false positive indications per image (mFPI) and partial area under the curve (AUC) with 1.0 mFPI for both test datasets were externally assessed with the test datasets. RESULTS: The hospital development dataset, hospital test dataset, clinic test dataset, and DDSM development dataset included a total of 3179 images (1448 malignant images), 491 images (225 malignant images), 2821 images (37 malignant images), and 1457 malignant images, respectively. The proposed model detected all cancers with a 0.45-0.47 mFPI and had partial AUCs of 0.93 in both test datasets. CONCLUSIONS: The DL-based model developed for this study was able to detect all breast cancers with a very low mFPI. Our DL-based model achieved the highest performance to date, which might lead to improved diagnosis for breast cancer.