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Rationale and Objectives: Current radiomics research primarily focuses on intratumoral regions and fixed peritumoral areas, lacking optimization for accurate Ki-67 prediction. This study aimed to develop machine learning (ML) models to analyze radiomic features from Automated Breast Volume Scanning (ABVS) images of different peritumoral region sizes to identify the optimal size for accurate preoperative Ki-67 prediction., Materials and Methods: A total of 668 breast cancer patients were enrolled and divided into training (486) and testing (182) cohorts. In the training cohort, ML models were developed for intratumoral and peritumoral regions (2, 4, 6, 8, and 10 mm). Relevant Ki-67 features for each ROI were identified, and different models were compared to determine the optimal one. These models were validated using a testing cohort to find the most accurate peritumoral region for Ki-67 prediction. SHAP (Shapley Additive Explanations) analysis was performed to identify key radiomic features from the optimal model., Results: The Extreme Gradient Boosting (XGBoost) model for the intratumoral region combined with the 6 mm peritumoral region achieved the highest predictive accuracy, with an AUC of 0.957 in the training cohort and 0.920 in the testing cohort. Calibration curves confirmed reliability, and decision curve analysis demonstrated the highest net benefit. SHAP indicated that 6 mm peritumoral radiomic features are more significant than intratumoral features., Conclusion: The XGBoost model using ABVS-derived radiomic features from both the intratumoral and 6 mm peritumoral regions provides the most accurate preoperative Ki-67 prediction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objectives: Previous studies have reported associations of noise and air pollution with breast cancer (BC) risk, but the causality remains unclear. This study aimed to explore the effects of noise and air pollution on BC from a genetic perspective., Study Design: Genetic association study., Methods: We began our investigation by visualizing the development trends in this field through bibliometric analysis. Subsequently, we conducted Mendelian randomization analyses to assess the effects of noise (daytime and evening) and air pollution (NO 2 , NO x , PM 2.5 , PM 2.5-10 , and PM 10 ) on BC. Genetic variants extracted from genome-wide association studies (GWAS) robustly associated with noise and air pollution were used as instrumental variables. The GWAS data for BC in European and East Asian populations were obtained from the Breast Cancer Association Consortium and the Biobank Japan, respectively., Results: The effects of noise and air pollution on BC are receiving increasing attention. In the European population, genetically predicted exposure to NO 2 (OR: 1.9381; 95% CI: 1.2873-2.9180; P = 0.0015) and PM 10 (OR: 1.4187; 95% CI: 1.0880-1.8500; P = 0.0098) were positively associated with overall BC risk. Subtype analyses showed that PM 10 was significantly related to the risks of both ER+ (OR: 1.6165; 95% CI: 1.1778-2.2186; P = 0.0030) and ER- (OR: 1.6228; 95% CI: 1.0175-2.5881; P = 0.0421) BC. Additionally, NO 2 only increased the risk of ER+ BC (OR: 1.7429; 95% CI: 1.0679-2.8444; P = 0.0262), but not ER- BC. In East Asians, genetically predicted NO 2 was positively related to BC risk (OR: 1.1394; 95% CI: 1.0082-1.2877; P = 0.0366)., Conclusions: Our study gave new evidence from a genetic standpoint underscoring that improving the environmental quality of residential areas is conducive to reducing BC risk., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Breast cancer ranks the first in the incidence of female cancer and is the most common cancer threatening the life and health of women worldwide.Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) is a pro-apoptotic gene downstream of p53. However, the role of TP53AIP1 in BC needs to be investigated. In vitro and in vivo experiments were conducted to assess the biological functions and associated mechanisms. Several bioinformatics analyses were made, CCK8 assay, wound healing, transwell assays, colony formation assay, EDU, flow cytometry, Immunofluorescence, qRT-PCR and Western-blotting were performed. In our study, we discovered that BC samples had low levels of TP53AIP1 expression, which correlated with a lower survival rate in BC patients. When TP53AIP1 was up-regulated, it caused a decrease in cell proliferation, migration, and invasion. It also induced epithelial-to-mesenchymal transition (EMT) and protective autophagy. Furthermore, the over-expression of TP53AIP1 suppressed tumor growth when tested in vivo. We also noticed that TP53AIP1 up-regulation resulted in decreased levels of phosphorylation in AKT and mTOR, suggesting a mechanistic role. In addition, we performed functional rescue experiments where the activation of AKT was able to counteract the impact of TP53AIP1 on the survival and autophagy in breast cancer cell lines. This suggests that TP53AIP1 acts as an oncogene by controlling the AKT/mTOR pathway. These findings reveal TP53AIP1 as a gene that suppresses tumor growth and triggers autophagy through the AKT/mTOR pathway in breast cancer cells. As a result, TP53AIP1 presents itself as a potential target for novel therapeutic approaches in treating breast cancer.

Objectives: Depression is associated with unhealthy autonomic regulation. However, whether patients with breast cancer (BC) with different degrees of depression can be identified from linear and non-linear dynamics in the autonomic nervous system is unclear. We aimed to evaluate the differences in linear and non-linear heart rate variability (HRV) parameters in patients with BC with different degrees of depression and the relationship between HRV parameters and depression and sleep disorders., Methods: A total of 115 patients with BC were enrolled. According to their Self-Rating Depression Scale (SDS) scores, the patients were divided into a non-depressed group, a mildly depressed group and a moderately to severely depressed group. The Pittsburgh Sleep Quality Index (PSQI), HRV, linear index (including time and frequency domains) and non-linear index (including Poincare plot, approximate entropy (ApEn) and short-term fluctuation slope (DFAα1)) were evaluated., Results: Compared with patients without depssion, patients with mild depression and moderate-to-severe depression had significant differences in the time domain, frequency domain index, the SD perpendicular to the line-of-identity (SD1) and DFAα1 of non-linear HRV and sleep quality. SDS and PSQI scores were correlated with HRV parameters., Conclusions: The severity of depression in patients with BC is associated with reduced variability, complexity of cardiac dynamics and sleep disturbance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Previous studies have indicated that histone methylations act as mediators in the relationship between oestrogen receptor (ER) and breast cancer prognosis, yet the mediating role has never been assessed. Therefore, we investigated seven histone methylations (H3K4me2, H3K4me3, H3K9me1, H3K9me2, H3K9me3, H3K27me3 and H4K20me3) to determine whether they mediate the prognostic impact of ER on breast cancer. Tissue microarrays were constructed from 1045 primary invasive breast tumours, and the expressions of histone methylations were examined by immunohistochemistry. Multifactorial logistic regression was used to analyse the associations between ER and histone methylations. Cox proportional hazard model was performed to assess the relationship between histone methylations and breast cancer prognosis. The mediation effects of histone methylations were evaluated by model-based causal mediation analysis. High expressions of H3K9me1, H3K9me2, H3K4me2, H3K27me3, H4K20me3 were associated with ER positivity, while high expression of H3K9me3 was associated ER negativity. Higher H3K9me2, H3K4me2 and H4K20me3 levels were associated with better prognosis. The association between ER and breast cancer prognosis was most strongly mediated by H4K20me3 (29.07% for OS; 22.42% for PFS), followed by H3K4me2 (11.5% for OS; 10.82% for PFS) and least by H3K9me2 (9.35% for OS; 7.34% for PFS). H4K20me3, H3K4me2 and H3K9me2 mediated the relationship between ER and breast cancer prognosis, which would help to further elucidate the impact of ER on breast cancer prognosis from an epigenetic perspective and provide new ideas for breast cancer treatment.

Purpose: To evaluate the feasibility of multiplexed sensitivity-encoding (MUSE) with deep learning-based reconstruction (DLR) for breast imaging in comparison with conventional diffusion-weighted imaging (DWI) and MUSE alone., Methods: This study was conducted using conventional single-shot DWI and MUSE data of female participants who underwent breast magnetic resonance imaging (MRI) from June to December 2023. The k-space data in MUSE were reconstructed using both conventional reconstruction and DLR. Two experienced radiologists conducted quantitative analyses of DWI, MUSE, and MUSE-DLR images by obtaining the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) of lesions and normal tissue and qualitative analyses by using a 5-point Likert scale to assess the image quality. Inter-reader agreement was assessed using the intraclass correlation coefficient (ICC). Image scores, SNR, CNR, and apparent diffusion coefficient (ADC) measurements among the three sequences were compared using the Friedman test, with significance defined at P < 0.05., Results: In evaluations of the images of 51 female participants using the three sequences, the two radiologists exhibited good agreement (ICC = 0.540-1.000, P < 0.05). MUSE-DLR showed significantly better SNR than MUSE (P < 0.001), while the ADC values within lesions and tissues did not differ significantly among the three sequences (P = 0.924, P = 0.636, respectively). In the subjective assessments, MUSE and MUSE-DLR scored significantly higher than conventional DWI in overall image quality, geometric distortion and axillary lymph node (P < 0.001)., Conclusion: In comparison with conventional DWI, MUSE-DLR yielded improved image quality with only a slightly longer acquisition time., Competing Interests: Declaration of competing interest GE HealthCare. B.Z and H.L.L are the employees of GE Healthcare. The data from this study was analyzed and controlled by authors who are not employees of the medical industry. The collaboration is on a purely scientific basis, and none of the authors and coauthors will derive any economic benefit from the publication. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs)., Methods: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up., Results: Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98)., Conclusions: Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) account for most cases of breast cancer. However, there is ongoing debate about any potential variations in overall survival (OS) between ILC and IDC. This study aimed to compare survival between IDC and ILC, identify prognostic factors for ILC patients, and construct a nomogram for predicting OS rates. This retrospective cohort analysis utilized data from the Surveillance, Epidemiology, and End Results (SEER) Cancer Database. Patients diagnosed with ILC and IDC between 2000 and 2019 were enrolled. To minimize baseline differences in clinicopathological characteristics and survival outcomes, a propensity score matching (PSM) method was used. Data from the multivariate Cox regression analyses were used to construct a predictive nomogram for OS at 1, 3, and 5 years, incorporating all independent prognostic factors. Following the PSM procedure, patients with ILC exhibited a better prognosis compared to those with IDC. TNM stage, age >70, radiotherapy, surgery, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HR-/HER2+) subtype were identified as independent factors for OS in ILC patients. Surgery and radiotherapy effectively reduced the risk of death, while chemotherapy did not demonstrate the same benefit. This model could support clinicians in evaluating the prognosis of ILC for decision-making and patient counseling.

MiR-1246 in breast cancer-derived exosomes was a promising biomarker for early diagnosis of breast cancer(BC). However, the low abundance, high homology and complex background interference make the accurate quantitative detection of miR-1246 facing great challenges. In this study, we developed an electrochemical biosensor based on the subtly combined of CRISPR/Cas12a, double-stranded specific nuclease(DSN) and magnetic nanoparticles(MNPs) for the detection of miR-1246 in BC-derived exosomes. Ascribed to the good synergistic effect of DSN, Cas12a and MNPs, the developed electrochemical biosensor exhibited excellent performance with the linear range from 500 aM to 5 pM, and the detection limit as low down to about 50 aM. The target-specific triggered enzyme-digest activity of DSN and Cas12a system, as well as the powerful separation ability of MNPs ensure the high specificity of developed electrochemical biosensor which can distinguish single base mismatches. In addition, the developed electrochemical biosensor has been successfully applied to detect miR-1246 in blood-derived exosomes and realize distinguishing the BC patients from the healthy individuals. It is expected that the well-designed biosensing platform will open up new avenues for clinical liquid biopsy and early screening of breast cancer, as well as provide deeper insights into clinical oncology treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Chlamydia trachomatis (C. trachomatis) infection has been implicated in various cancers, yet its association with breast cancer remains unexplored. This infection triggers a cascade of immune responses primarily regulated by Interleukins-12 (IL-12). Thus, the objective of this case-control study was to investigate the link between C. trachomatis infection and breast cancer risk, as well as the modification effect of IL-12., Methods: We assessed IgG levels against C. trachomatis in serum of 1,121 women with breast cancer (861 with estrogen receptor-positive (ER+) and 260 with estrogen receptor-negative (ER-) tumors) and 400 controls in Guangzhou, China. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer risk in association with C. trachomatis infection. The interaction between C. trachomatis infection and IL-12 on breast cancer risk was estimated by the product terms in the logistic regression models., Results: Seropositivity of C. trachomatis IgG showed a slight association with an increased risk of breast cancer (OR = 1.20; 95% CI: 0.86∼1.78). This association was more pronounced among women with a higher (OR = 5.82; 95% CI: 1.31∼25.94) than a lower (OR = 0.73; 95% CI: 0.41∼1.30) level of IL-12, with a statistically significant interaction observed (P interaction = 0.013). In addition, C. trachomatis IgG seropositivity was related to an increased risk of breast cancer among PR+ patients (OR = 1.53; 95% CI: 1.04∼2.23)., Conclusions: C. trachomatis infection may contribute to the development of hormone-responsive breast cancer in women with high levels of IL-12. Further studies are needed to uncover the underlying mechanisms., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance.

Objective: The main aim of this study was to determine whether the use of contrast-enhanced ultrasound (CEUS) could improve the categorization of suspicious breast lesions based on the Breast Imaging Reporting and Data System (BI-RADS), thereby reducing the number of benign breast lesions referred for biopsy., Methods: This prospective study, conducted between January 2017 and December 2018, enrolled consenting patients from eight teaching hospitals in China, who had been diagnosed with solid breast lesions classified as BI-RADS 4 using conventional ultrasound. CEUS was performed within 1 wk of diagnosis for reclassification of breast lesions. Histopathological results obtained from core needle biopsies or surgical excision samples served as the reference standard. The simulated biopsy rate and cancer-to-biopsy yield were used to compare the accuracy of CEUS and conventional ultrasound (US)., Results: Among the 1490 lesions diagnosed as BI-RADS 4 with conventional ultrasound, 486 malignant and 1004 benign lesions were confirmed based on histology. Following CEUS, 2, 395, and 211 lesions were reclassified as CEUS-based BI-RADS 2, 3, and 5, respectively, while 882 (59%) remained as BI-RADS 4. The actual cancer-to-biopsy yield based on US was 32.6%, which increased to 43.4% when CEUS-based BI-RADS 4A was used as the cut-off point to recommend biopsy. The simulated biopsy rate decreased to 73.4%. Overall, in this preselected BI-RADS 4 population, only 2.5% (12/486) of malignant lesions would have been miscategorized as BI-RADS 3 using CEUS-based reclassification. The diagnostic accuracy, sensitivity, and specificity of contrast-enhanced ultrasound reclassification were 57.65%, 97.53%, and 38.35%, respectively., Conclusion: Our collective findings indicate that CEUS is a valuable tool in further triage of BI-RADS category 4 lesions and facilitates a reduction in the number of biopsies while increasing the cancer-to-biopsy yield., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chemobrain is widespread in breast cancer patients receiving chemotherapy. However, the exact mechanism, especially the associated signalling pathway, is not currently clear. This study was to evaluate the behavioural changes in breast cancer mice after chemotherapy and to further explore the role of Wnt3a/glycogen synthase kinase (GSK3β)/β-catenin signalling in chemobrain., Methods: MMTV-PyMT(+) breast cancer mice were injected intraperitoneally with doxorubicin (4 mg/kg) once a week for three weeks to establish a chemobrain model. The Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and memory ability. Electron microscopy was used to observe the structural changes in the hippocampal CA1 region. The brain tissue of breast cancer mice after chemotherapy was taken out for mRNA-seq detection. Then, the expression levels and phosphorylation of key proteins in the Wnt3a/GSK3 β/β-catenin signalling pathway were evaluated through Western blotting (WB) and immunofluorescence., Results: Doxorubicin-induced spatial and short-term memory impairment was observed in breast cancer mice, and obvious neuronal damage could be seen in the hippocampal CA1 region. Immunofluorescence staining for GSK3β was increased. Wnt signalling pathway is highly enriched from mRNA-seq analysis, with GSK3β genes at important nodes. The relative protein levels of p-PI3K, p-AKT, p-GSK3 β, Wnt3a and TCF-1 were decreased significantly, while the p-β-catenin level was increased. After injection of the GSK3β inhibitor sb216763 (1 ng/0.5 µl/side), hippocampal neuronal injury was alleviated to some extent, and the changes in the expression of proteins upstream and downstream of this signalling pathway were reversed., Conclusion: Wnt3a/GSK3 β/β-catenin signalling is likely involved in doxorubicin-induced memory impairment. This result provides basic evidence for the further study of chemobrain in breast cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC., Methods: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan-Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135., Findings: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48-1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41-0.66, p < 0.0001). The PALOMA-3 study analysed 520 patients with MBC. Within the 153 HER2-0 patients, the palbociclib-fulvestrant group showed a significantly longer PFS than the placebo-fulvestrant group (hazard ratio = 0.54, 95% CI 0.30-0.95, p = 0.034). Among the 367 HER2-low-positive patients, palbociclib-fulvestrant improved PFS (hazard ratio = 0.39, 95% CI 0.28-0.54, p < 0.0001)., Interpretation: The combination of a CDK4/6 inhibitor with ET significantly improved PFS in HER2-low-positive patients, while for HER2-0 patients, benefits were primarily observed in patients who had progressed on previous ET. Furthermore, HER2-0 patients may derive limited benefits from first-line CDK4/6 inhibitor treatment. Further work is needed to validate these findings and to delineate patient subsets that are most likely to benefit from the combination of CDK4/6 inhibitors and ET as first-line treatments., Funding: None., Competing Interests: Declaration of interests JKP was the recipient of research funding by the Color Foundation (PI: Plichta). She serves on the National Comprehensive Cancer Network (NCCN) Breast Cancer Screening Committee. Both are unrelated to this work. She also receives funding from the National Institutes of Health (PI: Amundsen; K12HD043446). SMT holds the consulting or advisory role for Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi Sankyo, Gilead, Ellipses Pharma, 4D Pharma, OncoSec Medical Inc., BeyondSpring Pharmaceuticals, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Myovant, Zetagen, Umoja Biopharma, Menarini/Stemline, Aadi Biopharma, Bayer, which are unrelated to this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In HR+ /HER2- breast cancer patients with ≤ 3 positive axillary lymph nodes (ALNs), genomic tests can streamline chemotherapy decisions. Current studies, centered on tumor metrics, miss broader patient insights. Automated Breast Volume Scanning (ABVS) provides advanced 3D imaging, and its potential synergy with radiomics for ALN evaluation is untapped., Objective: This study sought to combine ABVS radiomics and clinical characteristics in a nomogram to predict ≤ 3 positive ALNs in HR+ /HER2- breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs), guiding clinicians in genetic test candidate selection., Methods: We enrolled 511 early-stage breast cancer patients: 362 from A Hospital for training and 149 from B Hospital for validation. Using LASSO logistic regression, primary features were identified. A clinical-radiomics nomogram was developed to predict the likelihood of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs. We assessed the discriminative capability of the nomogram using the ROC curve. The model's calibration was confirmed through a calibration curve, while its fit was evaluated using the Hosmer-Lemeshow (HL) test. To determine the clinical net benefits, we employed the Decision Curve Analysis (DCA)., Results: In the training group, 81.2% patients had ≤ 3 metastatic ALNs, and 83.2% in the validation group. We developed a clinical-radiomics nomogram by analyzing clinical characteristics and rad-scores. Factors like positive SLNs (OR=0.077), absence of negative SLNs (OR=11.138), lymphovascular invasion (OR=0.248), and rad-score (OR=0.003) significantly correlated with ≤ 3 positive ALNs. The clinical-radiomics nomogram, with an AUC of 0.910 in training and 0.882 in validation, outperformed the rad-score-free clinical nomogram (AUCs of 0.796 and 0.782). Calibration curves and the HL test (P values 0.688 and 0.691) confirmed its robustness. DCA showed the clinical-radiomics nomogram provided superior net benefits in predicting ALN burden across specific threshold probabilities., Conclusion: We developed a clinical-radiomics nomogram that integrated radiomics from ABVS images and clinical data to predict the presence of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs, aiding oncologists in identifying candidates for genomic tests, bypassing ALND. In the era of precision medicine, combining genomic tests with SLN biopsy refines both surgical and systemic patient treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections., Methods: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT 50 ) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed., Results: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients., Conclusion: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses., Methods: A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model., Results: The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse's illness perception significantly affected the patient's psychosocial adjustment (β = 0.095, p = 0.015); the patient's illness perception also significantly affected the spouse's psychosocial adjustment (β = 0.106, p = 0.033). Among them, the patient's psychosocial adjustment was found to be related to the patient's illness comprehensibility or coherence of illness (β = 0.433, p = 0.009), the spouse's emotional illness representation (β = 0.218, p = 0.037), and the spouse's illness comprehensibility or coherence of illness (β = 0.416, p = 0.007), while the spouse's psychosocial adjustment was only related to the spouse's illness comprehensibility or coherence of illness (β = 0.528, p = 0.007)., Conclusions: The psychosocial adjustment of breast cancer patients is affected by both their own and spouse's illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them., (© 2024. The Author(s).)

Previously, we found that patients with estrogen receptor (ER)-positive, HER2-low breast cancer are resistant to neoadjuvant chemotherapy (NACT) and have worse outcomes than those who achieve pathological complete response (pCR) after NACT. This study aimed to investigate the prognosis and influencing factors in these patients. A total of 618 patients with ER-positive breast cancer who received standard thrice-weekly NACT were enrolled, including 411 patients with ER-positive, HER2-low breast cancer. Data on the clinicopathological features of these patients before and after NACT were collected. Univariate and multivariate Cox regression analyses were used to identify the independent factors affecting 5-year disease-free survival (DFS). Among the ER-positive, HER2-low patients, 49 (11.9%) achieved a pCR after NACT. A significant difference in survival was observed between patients with and without residual disease after NACT. Additionally, changes in immunohistochemical markers and tumor stages before and after NACT were found to be significant. According to univariate and multivariate analyses, cN&#95;stage (P = 0.002), ER (P = 0.002) and Ki67 (P = 0.023) expression before NACT were significantly associated with 5-year DFS, while pT&#95;stage (P = 0.015), pN&#95;stage (P = 0.029), ER (P = 0.020) and Ki67 (P < 0.001) levels after NACT were related to 5-year DFS in ER-positive, HER2-low patients with residual disease. Our study suggested that high proliferation, low ER expression and advanced stage before and after NACT are associated with a poor prognosis, providing useful information for developing long-term treatment strategies for ER-positive, HER2-low breast cancer in patients with residual disease in the future., (© 2024. The Author(s).)

Background: Phthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity., Objectives: To examine the association between DEHP exposure and incidence of breast malignant neoplasm, carcinoma in situ and benign neoplasm., Methods: A total of 273,295 women from UK Biobank cohort were followed up for a median of 13.5 years. Disease information was collected from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of DEHP exposure were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. Cox proportional hazard model was employed to estimate the association between DEHP exposure and breast neoplasms., Results: The median (IQR) of baseline and yearly-average DEHP concentration were 8000.25 (interquartile range: 6657.85-11,948.83) and 8000.25 (interquartile range: 1819.93-11,359.55) μg/L. The highest quartile of baseline DEHP was associated with 1.11 fold risk of carcinoma in situ (95 % CI, 1.00, 1.23, p < 0.001) and 1.27 fold risk of benign neoplasm (95 % CI, 1.05, 1.54, p < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of malignant neoplasm (HR, 1.05; 95 % CI, 1.03, 1.07, p < 0.001), carcinoma in situ (HR, 1.08; 95 % CI, 1.04, 1.11, p < 0.001) and benign neoplasm (HR, 1.13; 95 % CI, 1.07, 1.20, p < 0.001). Stratification analysis showed no significant modification effects on the DEHP-neoplasm relationship by menopausal status or ethnicity but a suggestive higher risk in younger women and those who underwent oral contraceptive pill therapy. In sensitivity analysis, the associations remained when excluding the cases diagnosed within 2 years post baseline., Conclusions: Real-world level of DEHP exposure was associated with higher risk of breast neoplasms. Because of the health risks associated with DEHP, its release to the environment should be managed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinase-selective mTOR inhibitor 24 ( PT-88 ), which demonstrated an mTOR inhibitory IC 50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC 50 : 0.74 μM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.

Introduction: The programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3'-untranslated region of the PCD pathway genes and breast cancer outcomes., Methods: In this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months., Results: Among all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10-6, 8.5 × 10-8, 3.6 × 10-4, and 1.3 × 10-4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively., Conclusions: Our results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Zeng, Tang, Nie, Jin, Guo, Chen, Lin, Wang and Fu.)

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8) + myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8 + myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8 + myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser 772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1 , which caused TSPAN8 + myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8 + SIRT6 low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8 + myCAFs is a promising approach to circumvent chemoresistance.

Purpose: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 ( ESR1 )-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET)., Patients and Methods: Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2- advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator's choice of ET (n = 239)., Results: In the ESR1- mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1 -mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1 -mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia., Conclusion: The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1- mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

Purpose: The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer., Methods: Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI., Results: SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p < 0.05). The ORs indicate that depression and distress have the strongest associations with SI. Health status has a significant indirect effect (OR=-0.044, p = 0.005) and a strong total effect (OR=-0.485, p < 0.001) on SI, mediated by insomnia severity and emotional distress., Conclusions: There is a high SI prevalence among Chinese patients with advanced breast cancer. Our analysis revealed predictive pathways from poor health to heightened SI, mediated by emotional distress and insomnia. Regular management of distress and insomnia can decrease suicide risk in this vulnerable population., (© 2024. The Author(s).)

Metastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η 2  = 0.143), distress (F = 7.969, p = 0.010, partial η 2  = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η 2  = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η 2  = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = - 2.689, p = 0.011, Cohen's d = 0.940) and distress (T2&T0, t = - 2.453, p = 0.022, Cohen's d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population.Trial registration: This study is part of the "Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients" clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. ( https://www.chictr.org.cn/index.html )., (© 2024. The Author(s).)

Objectives: To investigate the relationship of pre-treatment MR image features (including breast density) and clinical-pathologic characteristics with overall survival (OS) in breast cancer patients receiving neoadjuvant chemotherapy (NAC)., Methods: This retrospective study obtained an approval of the institutional review board and the written informed consents of patients were waived. From October 2013 to April 2019, 130 patients (mean age, 47.6 ± 9.4 years) were included. The univariable and multivariable Cox proportional hazards regression models were applied to analyze factors associated with OS, including MR image parameters and clinical-pathologic characteristics., Results: Among the 130 included patients, 11 (8.5%) patients (mean age, 48.4 ± 11.8 years) died of breast cancer recurrence or distant metastasis. The median follow-up length was 70 months (interquartile range of 60-85 months). According to the Cox regression analysis, older age (hazard ratio [HR] = 1.769, 95% confidence interval [CI]): 1.330, 2.535), higher T stage (HR = 2.490, 95%CI:2.047, 3.029), higher N stage (HR = 1.869, 95%CI:1.507, 2.317), low breast density (HR = 1.693, 95%CI:1.391, 2.060), peritumoral edema (HR = 1.408, 95%CI:1.078, 1.840), axillary lymph nodes invasion (HR = 3.118, 95%CI:2.505, 3.881) on MR were associated with worse OS (all p < 0.05)., Conclusions: Pre-treatment MR features and clinical-pathologic parameters are valuable for predicting long-time OS of breast cancer patients after NAC followed by surgery. Low breast density, peritumoral edema and axillary lymph nodes invasion on pre-treatment MR images were associated with worse prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting., Methods: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses., Results: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]., Conclusion: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bevacizumab is used for the treatment of advanced malignant tumors; it acts by inhibiting angiogenesis. This study aimed to examine adverse events (AEs) of bevacizumab, especially hemorrhage, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database., Research Design and Methods: The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to analyze the AEs of bevacizumab using FAERS registration data from January 2004 to September 2022. Clinical information regarding hemorrhagic signals was further analyzed., Results: The number of bevacizumab-associated AE reports was 96,477. Our study found that 892 significant preferred terms (PTs) were spread throughout 25 organ systems. The system organ classes (SOCs) focus on general disorders, administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. A total of 2,847 bevacizumab-related hemorrhage cases were reported, and 37 hemorrhagic signals were identified. Hemorrhagic signals were focused on SOC levels in vascular, gastrointestinal, and nervous system disorders. Colorectal, lung, and breast cancers are the three most common malignancies associated with BV-induced hemorrhage., Conclusion: The AE report from the present study confirms the majority of label information for bevacizumab, while also identifying new AEs. In addition, this was a large descriptive study of bevacizumab-induced hemorrhage.

Purpose: To explore the process of coping with financial toxicity among young women with breast cancer and formulate a grounded theory that serves as a foundation for creating intervention strategies aimed at supporting cancer survivors., Methods: A qualitative study using the Corbin and Strauss variant of grounded theory. A series of in-depth interviews were carried out with young women with breast cancer (n = 29) using the theoretical sampling method. We analyzed data by coding core categories in the patients' coping processes and developing theory around these categories. Data collection and analysis were performed simultaneously., Results: A substantial theory of the process of coping with financial toxicity among young female breast cancer survivors was constructed. Two core concepts, suffering and adjustment, were identified. Young women with breast cancer suffered from financial toxicity, which was related to risk factors, coping resources, and unmet needs. To overcome financial toxicity, young women with breast cancer adjusted by reshaping consumption concept, re-dividing of family functions, re-planning of occupation career, and rebuilding life confidence., Conclusion: This qualitative study constructed a theory delineating the coping strategies employed by young women with breast cancer in response to financial toxicity, offering profound insights into the intricacies of cancer-related financial toxicity. Identifying risk factors, enhancing coping resources, and meeting unmet needs would be helpful to patients' adjustment to financial stress., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: This meta-analysis aims to comprehensively evaluate the efficacy and safety of T-DM1 in treating HER2-positive breast cancer, providing insights for clinical practice. We conducted a literature search in PubMed, Cochrane Library, and Embase databases up to September 2023, collecting randomized controlled trials and cohort studies on T-DM1 for HER2-positive breast cancer. Out of 316 initially retrieved articles, 12 studies meeting the quality and inclusion criteria were included after a rigorous screening process. We used RevMan 5.3 software for the meta-analysis, employing fixed or random-effect models. Odds ratios (RRs) and 95% confidence intervals (CIs) were calculated as effect size measures. We conducted sensitivity analyses and assessed publication bias to ensure the results' stability and reliability. In seven studies, T-DM1 treatment significantly prolonged OS in patients with HER2-positive breast cancer [hazard ratio (HR) = 0.70, 95% CI: 0.64-0.77, P < 0.01], and the effect was especially pronounced in patients with advanced disease (HR = 0.64, 95% CI: 0.54-0.76, P < 0.001). Analysis of pCR rates did not show a significant difference (OR = 0.91, 95% CI: 0.48-1.73, P = 0.77). In five studies, ORR improved, but the difference between the two groups was not significant (OR = 1.16, 95% CI: 0.66-2.05, P = 0.61). Analysis of progression-free survival (PFS) showed a significant improvement in the experimental group relative to the control group (HR = 0.69, 95% CI: 0.57-0.84, P = 0.0003). Regarding the incidence of total adverse events, no significant difference was seen between the two groups (OR = 2.16, 95% CI: 0.98-4.79, P = 0.06), but for specific adverse events, such as leukopenia and neutropenia, the T-DM1 group demonstrated a significant reduction relative to the other treatment regimens. The results underscore the potential of T-DM1 in enhancing survival among patients with advanced HER2-positive breast cancer, yet they also highlight variability in effectiveness concerning pCR rate and ORR. The findings on adverse effects underscore the necessity of a balanced consideration of T-DM1's risks and benefits. Future research should focus on a more detailed examination of responses in varied patient populations, long-term outcomes, and a thorough economic evaluation of T-DM1, along with an exploration into treatment resistance. This will provide a more nuanced understanding of T-DM1's role in the treatment landscape of HER2-positive breast cancer., (Copyright © 2024 Copyright: © 2024 Indian Journal of Cancer.)

Objective: Resilience is an important regulating factor for anxiety and depression in breast cancer. The Managing Cancer and Living Meaningfully (CALM) intervention has been confirmed to improve anxiety and depression in patients, but the role of resilience is still unclear. This study explores this issue., Methods: In this study, a cohort of 124 patients diagnosed with breast cancer was recruited and randomly assigned to either the intervention group (IG) or the control group (CG). In addition, we enrolled a group of cancer-free women (regular control group) and assessed their resilience. All patients were evaluated using the Connor-Davidson Resilience Scale (CD-RISC), Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Cancer Therapy (FACT-B) and Perceived Stress Scale (PSS) at different time points. The primary outcomes were resilience, quality of life, anxiety, depression, and perceived stress. A repeated measures ANOVA was used to compare the scores of the IG and CG groups. The relationship between resilience and quality of life was analyzed using Pearson's correlation test. The paired-sample t-test was used to compare the changes in each score at different time points., Results: The intervention group showed significant differences in resilience, adamancy, optimism, tenacity, anxiety, depression, perceived stress and QOL scores before and after 6, 12, and 24 weeks (F = 17.411, F = 226.55, F = 29.096, F = 50.67, F = 82.662, F = 105.39, F = 62.66, F = 72.43, F = 34.561, respectively; P < 0.001). Compared to the control group, the intervention group demonstrated significant improvement in resilience and quality of life (t = -11.517, p < 0.001; t = - 4.929, p < 0.001), as well as a significant reduction in anxiety, depression, and perceived stress scores (t = 5.891, p < 0.001; t = 2.654, p < 0.001; t = 4.932, p < 0.001). In the intervention group, a significant positive correlation was observed between resilience in breast cancer survivors and quality of life (QOL) scores. (before CALM treatment: r = 0.3204, P = 0.0111; after 6 weeks: r = 0.3619, P = 0.0038; after 12 weeks: r = 0.3355, P = 0.0077; after 24 weeks: r = 0.2801, P = 0.0274)., Conclusions: A positive impact of the CALM intervention can be seen in improved resilience and reduced anxiety and depression, supporting its use as an effective psychological management tool and intervention strategy in the early stages of long-term breast cancer recovery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer is malignant tumours in women. A large amount of data analysis shows that Metformin has been shown to play a significance role in reducing the risk of breast cancer, but the mechanism remains unclear. The hippo signalling pathway can be involved in the formation, metastasis and recurrence of breast cancer. When YAP/TAZ is activated, cells can overcome contact inhibition and enter a state of uncontrolled proliferation. Therefore, YAP/TAZ is considered a potential therapeutic target for breast cancer. Eighty breast cancer patients, forty cases of triple-negative and forty cases of HER-2+, were included in this study. In vitro and in vivo experiments were used to confirm the YAP/TAZ axis was involved in the effects of metformin on breast cancer. EMT plays an important role in breast cancer, including chemoresistance and tumour metastasis. Our results confirmed that YAP could modulate the activity of EMT, which in turn altered tumour resistance. Therefore, MET can inhibit EMT by reducing the expression of YAP, and finally achieve the therapeutic effect of breast cancer. Our findings support metformin as a novel YAP inhibitor and potentially as a novel breast cancer drug.

Purpose: Overactivated neddylation is considered to be a common event in cancer. Long non-coding RNAs (lncRNAs) can regulate cancer development by mediating post-translational modifications. However, the role of lncRNA in neddylation modification remains unclear., Methods: LncRNA cytochrome P450 family 1 subfamily B member 1 antisense RNA 1 (CYP1B1-AS1) expression in breast cancer tissues was evaluated by RT-PCR and TCGA BRCA data. Gain and loss of function experiments were performed to explore the role of CYP1B1-AS1 in breast cancer cell proliferation and apoptosis in vitro and in vivo. Luciferase assay, CHIP-qPCR assay, transcriptome sequencing, RNA-pulldown assay, mass spectrometry, RIP-PCR and Western blot were used to investigate the regulatory factors of CYP1B1-AS1 expression and the molecular mechanism of CYP1B1-AS1 involved in neddylation modification., Results: We found that CYP1B1-AS1 was down-regulated in breast cancer tissues and correlated with prognosis. In vivo and in vitro functional experiments confirmed that CYP1B1-AS1 inhibited cell proliferation and induced apoptosis. Mechanistically, CYP1B1-AS1 was regulated by the transcription factor, forkhead box O1 (FOXO1), and could be upregulated by inhibiting the PI3K/FOXO1 pathway. Moreover, CYP1B1-AS1 bound directly to NEDD8 activating enzyme E1 subunit 1 (NAE1) to regulate protein neddylation., Conclusion: This study reports for the first time that CYP1B1-AS1 inhibits protein neddylation to affect breast cancer cell proliferation, which provides a new strategy for the treatment of breast cancer by lncRNA targeting neddylation modification., (© 2023. The Author(s).)

Breast cancer, as a daunting global health threat, has driven an exponential growth in related research activity in recent decades. An area of research of paramount importance is protein synthesis, and the analysis of specific proteins inextricably linked to breast cancer. In this article, we undertake a bibliometric analysis of the literature on breast cancer and protein synthesis, aiming to provide crucial insights into this esoteric realm of investigation. Our approach was to scour the Web of Science database, between 2003 and 2022, for articles containing the keywords "breast cancer" and "protein synthesis" in their title, abstract, or keywords. We deployed bibliometric analysis software, exploring a range of measures such as publication output, citation counts, co-citation analysis, and keyword analysis. Our search yielded 2998 articles that met our inclusion criteria. The number of publications in this area has steadily increased, with a significant rise observed after 2003. Most of the articles were published in oncology or biology-related journals, with the most publications in Journal of Biological Chemistry, Cancer Research, Proceedings of the National Academy of Sciences of the United States of America, and Oncogene. Keyword analysis revealed that "breast cancer," "expression," "cancer," "protein," and "translation" were the most commonly researched topics. In conclusion, our bibliometric analysis of breast cancer and related protein synthesis literature underscores the burgeoning interest in this research. The focus of the research is primarily on the relationship between protein expression in breast cancer and the development and treatment of tumors. These studies have been instrumental in the diagnosis and treatment of breast cancer. Sustained research in this area will yield essential insights into the biology of breast cancer and the genesis of cutting-edge therapies., (© 2023. The Author(s).)

Since the exosomal protein level is related to many diseases, sensitive detection of exosomal protein is highly desirable. Here, we describe a polymer-sorted high-purity semiconducting carbon nanotubes (CNTs) films-based field-effect transistor (FET) biosensor for ultrasensitive and label-free detection of MUC1, a transmembrane protein highly expressed in breast cancer exosomes. Polymer-sorted semiconducting CNTs hold advantages including high purity (>99%), high CNT concentration, and short processing time (<1 h), but they are difficult to be stably functionalized with biomolecules because of lacking hanging bonds on their surface. To solve this issue, poly-lysine (PLL) was employed to modify the CNT films after they were deposited on the sensing channel surface of the fabricated FET chip. To specifically recognize the exosomal protein, sulfhydryl aptamer probes were immobilized on the gold nanoparticles (AuNPs) surface that was assembled on PLL substrate. The aptamer-modified CNT FET was capable of sensitively and selectively detecting exosomal MUC1 as high as 0.34 fg/mL. Moreover, the CNT FET biosensor was able to recognize breast cancer patients from healthy individuals by comparing the expression level of exosomal MUC1. The developed CNT FET biosensor is expected to be a novel assay for early diagnosis of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To provide person-centered symptom management, the interindividual variability in breast cancer patients merits further exploration. However, how sociodemographic and clinical characteristics influence symptom profile membership in endocrine therapy for breast cancer is still unknown., Objectives: This study aimed to explore symptom profiles of breast cancer patients undergoing endocrine therapy and to identify sociodemographic and clinical characteristics among symptom subgroup members., Methods: A cross-sectional study was conducted, and participants were invited to complete a general information questionnaire and Functional Assessment of Cancer Therapy-Endocrine Subscale. Latent profile analysis, univariate analysis, and multinomial logistic regression were performed to explore symptom profiles and identify interindividual variability., Results: Three distinct subgroups were identified: "all high" (9.8%), "all moderate but high sexual symptoms" (25.4%), and "all low" (64.8%). Age, body mass index, main payment source for medical expenses, type of endocrine therapy, and history of breast cancer treatment were factors that determined membership in these 3 symptom subgroups., Conclusion: Patients' demographic and clinical characteristics were associated with their endocrine therapy-related symptom profiles. In general, those younger in age who pay out of pocket for medical expenses, use aromatase inhibitors, present a history of chemotherapy, and have a higher body mass index have a greater risk of symptom burden., Implication for Practice: The findings of this study will contribute to implementing individual cancer care based on the characteristics and needs of patient subgroups, which may improve the allocation of medical resources and provide interventions tailored to patients' unique needs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale and Objectives: To propose a novel deep learning method incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound, evaluate its performance in reducing false positives for Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions, and compare its diagnostic performance with that of ultrasound experts., Materials and Methods: This study enrolled 163 breast lesions in 161 women from November 2018 to March 2021. Contrast-enhanced ultrasound and conventional ultrasound were performed before surgery or biopsy. A novel deep learning model incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound was proposed for minimizing the number of false-positive biopsies. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were compared between the deep learning model and ultrasound experts., Results: The AUC, sensitivity, specificity, and accuracy of the deep learning model in BI-RADS category 4 lesions were 0.910, 91.5%, 90.5%, and 90.8%, respectively, compared with those of ultrasound experts were 0.869, 89.4%, 84.5%, and 85.9%, respectively., Conclusion: The novel deep learning model we proposed had a diagnostic accuracy comparable to that of ultrasound experts, showing the potential to be clinically useful in minimizing the number of false-positive biopsies., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflflicts of interest., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Fear of cancer recurrence (FCR) and psychological distress are common psychological problems in breast cancer (BC) patients and ultimately affecting their health-related quality of life (HRQoL). Heart rate variability (HRV) can reflect the activity of the parasympathetic nervous system. However, the pathways through which HRV influences between FCR and HRQoL are unclear. This study preliminarily explored the intermediary role of HRV in FCR and HRQoL in BC patients., Methods: A total of 101 BC patients participated in this study. HRV parameters were measured by a 5-min dynamic electrocardiogram. FCR, psychological distress and HRQoL were evaluated by the Fear of disease progression simplified scale (FOP-Q-SF), Distress thermometer and SF-36 concise health survey. The intermediary effect model was established to test the intermediary effect of high frequency-HRV (HF-HRV) on FCR and HRQoL., Results: FCR and psychological distress were negatively correlated with HRV in the time domain, negatively correlated with HF-HRV in the frequency domain, and positively correlated with low frequency/high frequency (LF/HF). HF-HRV had a partial mediating effect on the FCR and physical health and mental health, with effects of 30.23% and 9.53%, respectively., Conclusion: FCR and psychological distress are correlated with HRV parameters in the time domain and the frequency domain, and we preliminarily believe that parasympathetic nerves play an important intermediary role between FCR and subjective physical and mental health. This may provide intervention information for improving the HRQoL of BC patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Breast cancer patients undergoing endocrine therapy experience various symptoms that have long-term effects on their quality of life. However, which symptom clusters are expressed and affect patients' quality of life remain significantly controversial. Therefore, we aimed to explore symptom clusters among breast cancer patients receiving endocrine therapy and identify the impact of these clusters on their quality of life., Data Sources: This secondary analysis of data from a cross-sectional study aimed to explore the symptom experiences and quality of life of breast cancer patients receiving endocrine therapy. The participants were invited to complete the Functional Assessment of Cancer Therapy-Breast (FACT-B) and Endocrine Subscale (ES). Principal component analysis, Spearman correlation analyses, and multiple linear regression were used to explore symptom clusters and identify their influence on quality of life., Conclusion: Data from 613 participants were obtained, and 19 symptoms were included in the principal component analysis, which identified five symptom clusters: the systemic, pain and emotional, sexual, vaginal, and vasomotor symptom clusters. Adjustment for covariates revealed that the systemic and pain and emotional symptom clusters were negative predictors of quality of life. The fitted model explained approximately 38.1% of the variance., Implications for Nursing Practice: This study demonstrated that breast cancer patients receiving endocrine therapy experienced symptoms that tended to occur in five clusters (i.e., systemic, pain and emotional, sexual, vaginal, and vasomotor symptoms). Developing interventions for the systemic and pain and emotional symptom clusters may effectively improve patients' quality of life., Competing Interests: Declaration of Competing Interest All authors declare that they do not have any actual or potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Breast cancer has the highest incidence rate among malignant tumors in China, with a trend of affecting younger women. The treatment has short- and long-term adverse effects such as damage to the ovaries, which may result in infertility. Such consequences then increase patients' concerns over future reproduction. At present, nor do medical staffs continuously assess their overall well-being, or ensure that they have the knowledge necessary to manage their reproductive concerns. This qualitative study aimed to explore psychological and reproductive decision-making experiences of young women who had experienced childbirth after their diagnosis., Methods: The phenomenological research, as a kind of qualitative study, was conducted on 12 young women who experienced childbirth after breast cancer diagnosis. Data collection was from September 2021 to January 2022 and content analysis method was used to analyze the data., Results: Five main themes were identified: (1) desire for childbearing from individual, familial, and social aspects after the diagnosis of breast cancer; (2) emotional experiences through pregnancy till raising children; (3) support needs from professionals, family, and peer; (4) self and doctors' influencing factors on reproductive decision-making; and (5) satisfaction with the outcome of reproductive decision-making., Conclusions: The desire for childbearing of young women should be considered during the reproductive decision-making process. A multidisciplinary team is suggested to be set up to provide professional support. During the reproductive process, professional and peer support should be strengthened to improve decision-making abilities, alleviate negative emotional experience, and smoothen the process of reproductive experience for young patients., (© 2023. The Author(s).)

Human epidermal growth factor receptor 2 (HER2) gene amplification helps identify breast cancer patients who may respond to targeted anti-HER2 therapy. This study aims to develop an automated method for quantifying HER2 fluorescence in situ hybridization (FISH) signals and improve the working efficiency of pathologists. An Aitrox artificial intelligence (AI) model based on deep learning was constructed, and a comparison between the AI model and traditional manual counting was performed. In total, 918 FISH images from 320 consecutive invasive breast cancers were analysed and automatically classified into 5 groups according to the 2018 ASCO/CAP guidelines. The overall classification accuracy was 85.33% (157/184) with a mean average precision of 0.735. In Group 5, the most common group, the consistency was as high as 95.90% (117/122), while the consistency was low in the other groups due to the limited number of cases. The causes of this inconsistency, including clustered HER2 signals, coarse CEP17 signals and some section quality problems, were analysed. The developed AI model is a reliable tool for evaluating HER2 amplification statuses, especially for breast cancer in Group 5; additional cases from multiple centres could further improve the accuracy achieved for other groups., (© 2023. The Author(s).)

Background and Aims: Leisure sedentary behavior (LSB) is associated with the risk of cancer, but the causal relationship between them has not been clarified. The aim of this study was to assess the potential causal association between LSB and risk of 15 site-specific cancers., Methods: The causal association between LSB and cancer were assessed with univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR). 194 SNPs associated with LSB (from the UK Biobank 408,815 individuals) were adopted as the instrument variables. Sensitivity analyses were performed to ensure the robustness of the results., Results: UVMR analysis revealed that television watching significantly increased the risk of endometrial cancer (OR = 1.29, 95% CI = 1.02-1.64, p = 0.04) (mainly the endometrioid histology [OR = 1.28, 95% CI = 1.02-1.60, p = 0.031])，breast cancer (OR = 1.16, 95% CI = 1.04-1.30, p = 0.007) (both ER+ breast cancer [OR = 1.17, 95% CI = 1.03-1.33, p = 0.015], and ER- breast cancer [OR = 1.55, 95% CI = 1.26-1.89, p = 2.23 × 10 -5 ]). Although causal association was not found between television watching and ovarian cancer, it was seen in low grade and low malignant potential serous ovarian cancer (OR = 1.49, 95% CI = 1.07-2.08, p = 0.018). However, significant results were not obtained in the UVMR analysis between driving, computer use and the 15 types of cancer. Further MVMR analysis indicated that the above results are independent from most metabolic factors and dietary habits, but mediated by educational attainment., Conclusion: LSB in form of television watching has independent causal association with the risk of endometrial cancer, breast cancer, and ovarian cancer., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Reproductive tract infections influenced a series of inflammatory processes which involved in the development of breast cancer, while the processes were largely affected by estrogen. The present study aimed to explore the associations of breast cancer risk and prognosis with reproductive tract infections and the modification effects of estrogen exposure., Methods: We collected history of reproductive tract infections, menstruation and reproduction from 1003 cases and 1107 controls and a cohort of 4264 breast cancer patients during 2008-2018 in Guangzhou, China. We used logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk; Cox model was applied to estimate the hazard ratios (HRs) and 95% CIs for progression-free survival (PFS) and overall survival (OS)., Results: It was found that previous reproductive tract infections were negatively associated with breast cancer risk (OR = 0.80, 95%CI, 0.65-0.98), particularly for patients with more menstrual cycles (OR = 0.74, 95%CI, 0.57-0.96). Patients with previous reproductive tract infections experienced better OS (HR = 0.61; 95% CI, 0.40-0.94) and PFS (HR = 0.84; 95% CI, 0.65-1.09). This protective effect on PFS was only found in patients with more menstrual cycles (HR = 0.52, 95% CI:0.34-0.79, P interaction  = 0.015)., Conclusions: The findings suggested that reproductive tract infections may be protective for the initiation and development of breast cancer, particularly for women with a longer interval of lifetime estrogen exposure., (© 2023. The Author(s).)

Importance: The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown., Objective: To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality., Design, Setting, and Participants: The Diet, Exercise, Lifestyles, and Cancer Prognosis Study (DELCaP) was a prospective, observational cohort study designed to assess lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment completion, implemented ancillary to the Southwest Oncology Group (SWOG) S0221 trial, a multicenter trial that compared chemotherapy regimens in breast cancer. Participants were chemotherapy-naive patients with pathologic stage I to III high-risk breast cancer, defined as node-positive disease with hormone receptor-negative tumors larger than 1 cm or any tumor larger than 2 cm. Patients with poor performance status and comorbidities were excluded from S0221. The study was conducted from January 1, 2005, to December 31, 2010; mean (SD) follow-up time for those not experiencing an event was 7.7 (2.1) years through December 31, 2018. The analyses reported herein were performed from March 2022 to January 2023., Exposure: An aggregated lifestyle index score comprising data from 4 time points and 7 lifestyles, including (1) physical activity, (2) body mass index, (3) fruit and vegetable consumption, (4) red and processed meat intake, (5) sugar-sweetened beverage consumption, (6) alcohol consumption, and (7) smoking. Higher scores indicated healthier lifestyle., Main Outcomes and Measures: Disease recurrence and all-cause mortality., Results: A total of 1340 women (mean [SD] age, 51.3 [9.9] years) completed the baseline questionnaire. Most patients were diagnosed with hormone-receptor positive breast cancer (873 [65.3%]) and completed some education beyond high school (954 [71.2%]). In time-dependent multivariable analyses, patients with highest vs lowest lifestyle index scores experienced a 37.0% reduction in disease recurrence (hazard ratio, 0.63; 95% CI, 0.48-0.82) and a 58.0% reduction in mortality (hazard ratio, 0.42; 95% CI, 0.30-0.59)., Conclusions and Relevance: In this observational study of patients with high-risk breast cancer, strongest collective adherence to cancer prevention lifestyle recommendations was associated with significant reductions in disease recurrence and mortality. Education and implementation strategies to help patients adhere to cancer prevention recommendations throughout the cancer care continuum may be warranted in breast cancer.

Introduction: There is increasing awareness of the role of adipose tissue in breast cancer occurrence and development, but no comparison of adipose adjacent to breast cancer tissues and adipose adjacent to normal breast tissues has been reported., Methods: Single-nucleus RNA sequencing (snRNA-seq) was used to analyze cancer-adjacent and normal adipose tissues from the same breast cancer patient to characterize heterogeneity. SnRNA-seq was performed on 54513 cells from six samples of normal breast adipose tissue (N) distant from the tumor and tumor-adjacent adipose tissue (T) from the three patients (all surgically resected)., Results and Discussion: Significant diversity was detected in cell subgroups, differentiation status and, gene expression profiles. Breast cancer induces inflammatory gene profiles in most adipose cell types, such as macrophages, endothelial cells, and adipocytes. Furthermore, breast cancer decreased lipid uptake and the lipolytic phenotype and caused a switch to lipid biosynthesis and an inflammatory state in adipocytes. The in vivo trajectory of adipogenesis revealed distinct transcriptional stages. Breast cancer induced reprogramming across many cell types in breast cancer adipose tissues. Cellular remodeling was investigated by alterations in cell proportions, transcriptional profiles and cell-cell interactions. Breast cancer biology and novel biomarkers and therapy targets may be exposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Li, Xie and Huo.)

Objectives: Ultrasound examination has inter-observer and intra-observer variability and a high false-positive rate. The aim of this study was to evaluate the value of the combined use of a deep learning-based computer-aided diagnosis (CAD) system and ultrasound elastography with conventional ultrasound (US) in increasing specificity and reducing unnecessary breast lesions biopsies., Materials and Methods: Conventional US, CAD system, and strain elastography (SE) were retrospectively performed on 216 breast lesions before biopsy or surgery. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and biopsy rate were compared between conventional US and the combination of conventional US, SE, and CAD system., Results: Of 216 lesions, 54 were malignant and 162 were benign. The addition of CAD system and SE to conventional US increased the AUC from 0.716 to 0.910 and specificity from 46.9% to 85.8% without a loss in sensitivity while 89.2% (66 of 74) of benign lesions in Breast Imaging Reporting and Data System (BI-RADS) category 4A lesions would avoid unnecessary biopsies., Conclusion: The addition of CAD system and SE to conventional US improved specificity and AUC without loss of sensitivity, and reduced unnecessary biopsies., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Chemotherapy-related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI., Methods: This study enrolled one hundred and twenty-four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single-nucleotide polymorphisms (SNP) to explore these. The mini-mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT)., Results: We found that patients with ALDH2 gene genotypes of rs671&#95;GG, rs886205&#95;GG, rs4648328&#95;CC, and rs4767944&#95;TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671&#95;GG of DST (z = 2.769, p = 0.006), VFT (t = 4.624, P<0.001); rs886205&#95;GG of DST (z = 3.663, P<0.001); rs4648328&#95;CC of DST (z = 2.850, p = 0.004), VFT (t = 3.477, p = 0.001); and rs4767944&#95;TT of DST (z = 2.967, p = 0.003), VFT (t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious., Conclusion: Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single-nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown., Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture., Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37)., Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy., Implications for Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objectives: A considerable number of benign lesions, especially category 4a lesions on Breast Imaging Reporting and Data System Magnetic Resonance Imaging (BI-RADS-MRI), were biopsied according to BI-RADS-MRI, which was a diagnostic imaging challenge. This study aimed to evaluate the diagnostic performance of ultrasound elastography (UE) assisted Breast Imaging Reporting and Data System (BI-RADS) for BI-RADS-MRI category 4a lesions., Methods: Between January 2017 and December 2019, 228 breast lesions categorized as BI-RADS-MRI 4a were included. Conventional ultrasound (US) and UE were performed to evaluate each lesion. Pathology results were used as the gold standard. The diagnostic performances of different UE methods and our re-assessment proposal were evaluated., Results: When BI-RADS-MRI category 4a, BI-RADS-US category 3-4a, the stiffness of soft or intermediate in elasticity assessment according to the fifth edition of the BI-RADS atlas, strain ratio < 1.335, age ≤ 52 years, and the maximum diameter of lesion ≤20 mm were simultaneously met, an ultrasound-guided empty needle biopsy was not recommended, but short-term ultrasound follow-up for 3-6 months was recommended, and biopsy was performed after changes in evaluation. In this way, 95 of 228 BI-RADS-MRI category 4a lesions avoided biopsies, and the number of patients with biopsies decreased by 41.7%., Conclusions: UE offers benefits in the characterization of BI-RADS-MRI category 4a lesions. Ultrasound and elastography can help optimize therapy recommendations for BI-RADS-MRI category 4a lesions by our re-assessment proposal., (© 2022 American Institute of Ultrasound in Medicine.)