Journal of Breast Cancer最新文献

Purpose: The epithelial-to-mesenchymal transition (EMT) is the main event that favors cell migration and metastasis in breast cancer. Previously, we demonstrated that 1 nM estradiol (E₂) promotes EMT, induced by c-Src kinase, causing changes in the localization of proteins that compose the tight junction (TJ) and adherens junction (AJ).

Methods: The present work highlights the central role of c-Src in the initiation of metastasis, induced by E₂, through increasing the ability of MCF-7 and T47-D cells, which express estrogen receptor alpha (ERα), to migrate and invade before they become metastatic.

Results: Treatment with E₂ can activate two signaling pathways, the first one by the phosphorylated c-Src (p-Src) which forms the p-Src/E-cadherin complex. This phenomenon was completely prevented by incubation with a selective inhibitor of c-Src (5 µM PP2). p-Src then promotes the downregulation of E-cadherin and occludin, which are epithelial phenotype marker proteins of the AJ and TJ, respectively. In the second pathway, E₂ binds to ERα, creating a complex that translocates to the nucleus, inducing the synthesis of SNAIL1 and N-cadherin proteins, markers of the mesenchymal phenotype. Both processes increased the migratory and invasive capacities of both cell lines.

Conclusion: The present study demonstrate that E₂ enhance EMT and migration, through c-Src activation, in human breast cancer cells that express ERα and become potential therapeutic targets.

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

Despite recent advances in artificial intelligence (AI) software with improved performance in mammography screening for breast cancer, insufficient data are available on its performance in detecting cancers that were initially missed on mammography. In this study, we aimed to determine whether AI software-aided mammography could provide additional value in identifying cancers detected through supplemental screening ultrasound. We searched our database from 2017 to 2018 and included 238 asymptomatic patients (median age, 50 years; interquartile range, 45-57 years) diagnosed with breast cancer using supplemental ultrasound. Two unblinded radiologists retrospectively reviewed the mammograms using commercially available AI software and identified the reasons for missed detection. Clinicopathological characteristics of AI-detected and AI-undetected cancers were compared using univariate and multivariate logistic regression analyses. A total of 253 cancers were detected in 238 patients using ultrasound. In an unblinded review, the AI software failed to detect 187 of the 253 (73.9%) mammography cases with negative findings in retrospective observations. The AI software detected 66 cancers (26.1%), of which 42 (63.6%) exhibited indiscernible findings obscured by overlapping dense breast tissues, even with the knowledge of magnetic resonance imaging and post-wire localization mammography. The remaining 24 cases (36.4%) were considered interpretive errors by the radiologists. Invasive tumor size was associated with AI detection after multivariable analysis (odds ratio, 2.2; 95% confidence intervals, 1.5-3.3; p < 0.001). In the control group of 160 women without cancer, the AI software identified 19 false positives (11.9%, 19/160). Although most ultrasound-detected cancers were not detected on mammography with the use of AI, the software proved valuable in identifying breast cancers with indiscernible abnormalities or those that clinicians may have overlooked.

Purpose: In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer.

Methods: Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edema-negative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson's χ² test, Kaplan-Meier estimator, and Cox proportional hazards model.

Results: There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively. The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs. 19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56-9.11) and recurrence-free survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94-4.63) than those in the ENG. After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05-27.15).

Conclusion: Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer. Currently, no effective treatment options for this condition exist. Nuclear factor erythroid 2-related factor 2 (NRF2), encoded by nuclear factor erythroid-derived 2-like 2 (NFE2L2) gene and its endogenous inhibitor, Kelch-like ECH-associated protein 1 (KEAP1), both participate in cellular defense mechanisms against oxidative stress and contribute to chemoresistance and tumor progression in numerous types of cancers. This study aimed to evaluate the expression patterns of NRF2 and KEAP1 and their prognostic value in operable TNBC.

Methods: Tissue microarrays were prepared using tumor tissues collected from 203 patients with TNBC who underwent surgery. Immunohistochemical staining analyses of NRF2 and KEAP1 were performed. The expression of each immunomarker was categorized into two groups (low or high) based on the median H-score. We analyzed the association between the expression of each immunomarker and clinicopathological information to predict survival. A total of 225 TNBC samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate our results.

Results: NRF2 immunoreactivity was detected in the nucleus and was associated with histologic grade and Ki-67 index, whereas KEAP1 immunoreactivity was detected in the cytoplasm and was associated with the Ki-67 index. Survival analyses showed that NRF2 and KEAP1 expressions were independent prognostic factors for overall survival (OS) (hazard ratio [HR], 2.45 and 0.30; p = 0.015 and 0.016, respectively) and disease-free survival (HR, 2.27 and 0.42; p = 0.019 and 0.022, respectively). NFE2L2 mRNA expression was an independent prognostic factor for OS (HR, 0.59; p = 0.009) in the METABRIC dataset.

Conclusion: High NRF2 and low KEAP1 expressions independently predicted poor survival in patients with operable TNBC. Further investigations are warranted to examine the possible therapeutic benefits of targeting the KEAP1-NRF2 pathway for TNBC treatment.

Pseudoangiomatous stromal hyperplasia (PASH) is a rare idiopathic proliferative mesenchymal breast disease related to hormonal imbalance, and thus extremely rare in children and adolescents. In addition, PASH manifests as a bilateral gigantomastia in some cases with no established cause or treatment. Here, we report a case of a rapidly developed PASH presenting with bilateral gigantomastia in a 14-year-old premenarchial female patient. Considering the patient's age and emotions and the need for nipple-areolar complex repositioning, we performed reduction mammoplasty rather than total mastectomy despite the possibility of recurrence. Although some masses could not be completely removed, no complications, such as infection, wound dehiscence, or hematoma occurred postoperatively. The patient was stable during the 18-month follow-up period, although an evidence of recurrent and residual disease was noted upon ultrasonography.

Purpose: This study aimed to analyze the waiting time for initial treatment after breast cancer diagnosis and determine the factors influencing treatment delay in South Korea.

Methods: This nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment data. The participants were classified according to the regions where their biopsy and treatment were performed (Seoul-Seoul, Metro-Metro, Other-Other, Metro-Seoul, Other-Seoul). Waiting time was analyzed according to regional subgroup, year of diagnosis, and type of treatment. Multivariable logistic regression models were constructed to identify the factors associated with treatment delay (after 30 days of diagnosis).

Results: A total of 133,514 participants newly diagnosed between January 2010 and December 2017 were included in the study. The median waiting time for initial treatment in the total population increased from 8 days, in 2010, to 14 days, in 2017. In the Seoul-Seoul group, the waiting time increased from 10 days, in 2010, to 16 days, in 2017. Although the median waiting time was approximately 10 days in the Metro-Metro and Other-Other groups, it was 27 and 24 days, in the Metro-Seoul and Other-Seoul group, respectively, in 2017. The proportion of delayed upfront surgery by more than 30 days was higher in the Metro-Seoul (odds ratio [OR], 8.088; 95% confidence interval [CI], 7.357-8.893; p < 0.001) and Other-Seoul (OR, 6.210; 95% CI, 5.717-6.750; p < 0.001) groups than in the Metro-Metro (OR, 1.468; 95% CI, 1.352-1.594; p < 0.001) and Other-Other (reference) groups. Previous medical history and treatment at tertiary hospital were observed as factors related to delayed surgery.

Conclusion: Waiting times for breast cancer surgery have increased across all regions of Korea, with those traveling to Seoul experiencing particularly long wait times.

Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.

Purpose: Latissimus dorsi mini-flap (LDMF) reconstruction after breast-conserving surgery (BCS) is a useful volume replacement technique when a large tumor is located in the upper or outer portion of the breast. However, few studies have reported the impact of LDMF on patients' quality of life (QoL) and cosmesis compared with conventional BCS.

Methods: We identified patients who underwent BCS with or without LDMF between 2010 and 2020 at a single center. At least 1 year after surgery, we prospectively administered the BREAST-Q to assess QoL and obtained the patients' breast photographs. The cosmetic outcome was assessed using four panels composed of physicians and the BCCT.core software.

Results: A total of 120 patients were enrolled, of whom 62 and 58 underwent LDMF or BCS only, respectively. The LDMF group had significantly larger tumors, shorter nipple-to-tumor distances in preoperative examinations, and larger resected breast volumes than did the BCS-only group (p < 0.001). The questionnaires revealed that QoL was poorer in the LDMF group, particularly in terms of the physical well-being score (40.9 vs. 20.1, p < 0.001). Notably, the level of patients' cosmetic satisfaction with their breasts was comparable, and the cosmetic evaluation was assessed by panels and the BCCT.core software showed no differences between the groups.

Conclusion: Our results showed that cosmetic outcomes of performing LDMF are comparable to those of BCS alone while having the advantage of resecting larger volumes of breast tissue. Therefore, for those who strongly wish to preserve the cosmesis of their breasts, LDMF can be considered a favorable surgical option after the patient is oriented toward the potential for physical dysfunction after surgery.

This corrects the article on p. 292 in vol. 26, PMID: 37272245.