Journal of Breast Cancer最新文献

Breast cancer is a significant cause of cancer-related mortality in women worldwide. Early and precise diagnosis is crucial, and clinical outcomes can be markedly enhanced. The rise of artificial intelligence (AI) has ushered in a new era, notably in image analysis, paving the way for major advancements in breast cancer diagnosis and individualized treatment regimens. In the diagnostic workflow for patients with breast cancer, the role of AI encompasses screening, diagnosis, staging, biomarker evaluation, prognostication, and therapeutic response prediction. Although its potential is immense, its complete integration into clinical practice is challenging. Particularly, these challenges include the imperatives for extensive clinical validation, model generalizability, navigating the "black-box" conundrum, and pragmatic considerations of embedding AI into everyday clinical environments. In this review, we comprehensively explored the diverse applications of AI in breast cancer care, underlining its transformative promise and existing impediments. In radiology, we specifically address AI in mammography, tomosynthesis, risk prediction models, and supplementary imaging methods, including magnetic resonance imaging and ultrasound. In pathology, our focus is on AI applications for pathologic diagnosis, evaluation of biomarkers, and predictions related to genetic alterations, treatment response, and prognosis in the context of breast cancer diagnosis and treatment. Our discussion underscores the transformative potential of AI in breast cancer management and emphasizes the importance of focused research to realize the full spectrum of benefits of AI in patient care.

Trastuzumab deruxtecan (T-DXd) is used to treat human epidermal growth factor receptor 2-positive advanced breast cancer. Interstitial lung disease (ILD) is a severe adverse event associated with T-DXd. Current guidelines recommend permanent discontinuation of T-DXd after Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 ILD. Here, we describe a case of successful rechallenge with T-DXd after CTCAE grade 2 treatment-induced ILD. After discontinuation of T-DXd, ILD was treated with steroids until complete resolution. Given the initial beneficial antitumor response, retreatment was discussed during disease progression. In a shared decision with the patient, T-DXd was restarted at the lowest registered dose, along with low-dose steroids. ILD did not reoccur. Importantly, both clinical and radiological responses to the treatment were observed, with an improvement in the patient's quality of life. This case demonstrates that retreatment with T-DXd after a grade 2 ILD event is feasible and yields clinical benefit.

Purpose: The preemptive use of renin-angiotensin system (RAS) inhibitors may reduce doxorubicin (DOX)-related cardiotoxicity. Using the national insurance claims data of Korea, this study compared cardiovascular (CV) outcomes following the use of four major antihypertensive drug classes in patients with hypertension and breast cancer who underwent DOX-containing chemotherapy.

Methods: A total of 4,722 patients with hypertension and breast cancer who underwent DOX-containing chemotherapy were included. The outcomes were compared between patients who used RAS inhibitors, calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide and thiazide-like diuretics (TDs). The primary outcome was a composite of incident heart failure and serious ventricular arrhythmias, including ventricular tachycardia and fibrillation, ischemic heart disease, and stroke.

Results: In the propensity score-matched population, there were no significant differences in the primary outcome between RAS inhibitor and CCB users; however, patients with diabetes who used CCBs had a worse primary outcome than those who used RAS inhibitors (adjusted hazard ratio [aHR], 1.93; 95% confidence interval [CI], 1.06-3.51). BB and TD users had a worse primary outcome compared with RAS inhibitor (aHR, 1.88; 95% CI, 1.30-2.71 in BB users and aHR, 2.55; 95% CI, 1.37-4.75 in TD users) or CCB (aHR, 1.54; 95% CI, 1.09-2.16 in BB users and aHR, 2.08; 95% CI, 1.13-3.82 in TD users) users.

Conclusion: RAS inhibitors are preferred for the treating hypertension and improving CV outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy, particularly in patients with comorbid diabetes. However, CCBs are equivalent to RAS inhibitors and are more favorable than BBs and TDs in terms of improving CV outcomes.

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: 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.

Purpose: Improving survival and health-related quality of life (HRQOL), along with symptom relief, is important for the treatment of metastatic breast cancer (MBC). This study measured HRQOL and analyzed its influence on sociodemographic and clinical factors in patients with MBC.

Methods: We interviewed 298 patients with MBC to investigate their sociodemographic characteristics and HRQOL by using EuroQol-5D-5L (EQ-5D) between September and October 2014. We also reviewed medical records to examine the clinical condition of the patients, including disease progression, adverse events, treatments, chronic disease, and metastatic areas. The distribution of the EQ-5D index was compared between different clinical conditions by using the Kruskal-Wallis test. We also conducted multiple regression analyses to identify the factors affecting HRQOL in patients with MBC.

Results: The mean EQ-5D index was 0.79 for all patients surveyed. The mean EQ-5D index score was significantly lower in patients in the progressed state than in those in the progression-free survival state (0.73 vs. 0.80, p = 0.0002). The HRQOL of patients treated with chemotherapy alone was significantly lower than that of patients treated with hormonal or targeted therapy (0.76 vs. 0.82 or 0.85; p = 0.0020). Regression analysis revealed that the clinical factors associated with lower HRQOL were progressed state, chemotherapy, and adverse events, such as hair loss or stomatitis. Finally, young age, high income, and employment were the sociodemographic factors that were positively associated with better HRQOL.

Conclusion: This study provides new information on the health utility of MBC patients on the basis of various patient characteristics and offers insights that can assist medical professionals in treating patients with MBC and help policymakers implement cancer strategies. Further research is needed to reflect the changing environment of cancer treatment and enrich available evidence.

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.