Breast Cancer Research Articles

Long-term exposure to air pollution and breast cancer considering residential and workplace addresses and commutes: a French nested case-control study

Long-term exposure to air pollution and breast cancer considering residential and workplace addresses and commutes: a French nested case-control study

Breast cancer is associated with mixtures of organochlorine pesticides and metals in Mexican women

Breast cancer is associated with mixtures of organochlorine pesticides and metals in Mexican women

Genome-wide DNA methylation profiles and breast cancer among WTC survivors

Genome-wide DNA methylation profiles and breast cancer among WTC survivors

Wavelength-resolved measures of outdoor artificial light-at-night and risks of breast, prostate, and colorectal cancer

Wavelength-resolved measures of outdoor artificial light-at-night and risks of breast, prostate, and colorectal cancer

Chemical exposomics in plasma from Swedish women and associations with breast cancer risk factors

Chemical exposomics in plasma from Swedish women and associations with breast cancer risk factors

Using indocyanine green and methylene blue for axillary reverse mapping in modified radical mastectomy for breast cancer

Using indocyanine green and methylene blue for axillary reverse mapping in modified radical mastectomy for breast cancer

Heat exposure and breast cancer risk in the Sister Study

Heat exposure and breast cancer risk in the Sister Study

Neighborhood disadvantage and breast cancer incidence among women living in the United States

Neighborhood disadvantage and breast cancer incidence among women living in the United States

Temporal associations between fine particulate matter exposure and breast cancer incidence in the Sister Study

Temporal associations between fine particulate matter exposure and breast cancer incidence in the Sister Study

Prospective metabolome-wide association study suggests environmental chemicals cause early-onset breast cancer through disruption of nutrient sensing mechanisms

Prospective metabolome-wide association study suggests environmental chemicals cause early-onset breast cancer through disruption of nutrient sensing mechanisms

Association of Acute Incidental Cerebral Microinfarcts With Subsequent Ischemic Stroke in Patients With Cancer: A Population-Based Study.

Incidental diffuse-weighted imaging (DWI)-positive subcortical and cortical lesions, or acute incidental cerebral microinfarcts (CMIs), are a common type of brain ischemia, which can be detected on magnetic resonance DWI for approximately 2 weeks after occurrence. Acute incidental CMI was found to be more common in patients with cancer. Whether acute incidental CMI predicts future ischemic stroke is still unknown. We aimed to examine the association between acute incidental CMI in patients with cancer and subsequent ischemic stroke or transient ischemic attack (TIA). This is a retrospective cohort study. We used Clalit Health Services records, representing over half of the Israeli population, to identify adults with lung, breast, pancreatic, or colon cancer who underwent brain MRI between January 2014 and April 2020. We included patients who underwent scan between 1 year before cancer diagnosis and 1 year after diagnosis. Primary outcome was ischemic stroke or TIA using International Classification of Diseases, Ninth Revision codes. Secondary outcomes were intracranial hemorrhage (ICH) and mortality. Records were followed from first MRI until primary outcome, death, or end of follow-up (January 2023). Cox proportional hazards models were used to calculate hazard ratio (HR) for patients with and without acute incidental CMI, as a time-dependent covariate. The study cohort included 1,618 patients with cancer, among whom, 59 (3.6%) had acute incidental CMI on at least 1 brain MRI. The median (interquartile range) time from acute incidental CMI to stroke or TIA was 26 days (14-84). On multivariable analysis, patients with acute incidental CMI had a higher stroke or TIA risk (HR 2.97, 95% CI 1.08-8.18, p = 0.035) compared with their non-CMI counterparts. Acute incidental CMIs were also associated with mortality after multivariable analysis (HR 2.76, 95% CI 2.06-3.71, p < 0.001); no association with ICH was found. Acute incidental CMI on brain MRI in patients with active cancer is associated with an increased risk of near-future ischemic stroke or TIA and mortality. This finding might suggest that randomly detected acute incidental CMI in patients with cancer may guide primary cerebrovascular risk prevention and etiologic workup.

The Construction of Peer Support Among Recently Diagnosed Breast Cancer Patients.

Breast cancer (BC) and its treatments decrease patients' psychological well-being. Peer support is one form of social support, but little is known about what gives rise to peer support. The purpose of this study was to examine how peer support is constructed among recently diagnosed BC patients. Eighteen women were randomly picked from 130 women who had received phone calls from a trained peer supporter and were invited to group interviews. In the interviews, patients discussed their cancer, peer support experiences, and social support. The transcribed data were analyzed using Braun and Clarke's thematic analysis approach. The construction of peer support among newly diagnosed BC patients was complex. It depended on the needs of the patient and the success of interactions. Once they had received a diagnosis, the lives of the patients changed suddenly, and patients dove into the I-we-others consideration and had a need to talk. Interaction with peer supporters gave them a chance to share their stories. At their best, interactions led to belonging, caring, and a sense of security. The need to be heard and seen is strong in a patient's changing health situation. Peer support plays an important role in high-standard care and in strengthening patients' self-determination. Hospitals should create chances for supportive communication, and the supportive communication should be easily accessible and successful. The training of peer supporters should ensure that they have reflected on their own BC process and know how to consider the needs of newly diagnosed patients.

Oncogenic transcription factors instruct promoter-enhancer hubs in individual triple negative breast cancer cells.

Sequencing-based mapping of ensemble pairwise interactions among regulatory elements support the existence of topological assemblies known as promoter-enhancer hubs or cliques in cancer. Yet, prevalence, regulators, and functions of promoter-enhancer hubs in individual cancer cells remain unclear. Here, we systematically integrated functional genomics, transcription factor screening, and optical mapping of promoter-enhancer interactions to identify key promoter-enhancer hubs, examine heterogeneity of their assembly, determine their regulators, and elucidate their role in gene expression control in individual triple negative breast cancer (TNBC) cells. Optical mapping of individual SOX9 and MYC alleles revealed the existence of frequent multiway interactions among promoters and enhancers within spatial hubs. Our single-allele studies further demonstrated that lineage-determining SOX9 and signaling-dependent NOTCH1 transcription factors compact MYC and SOX9 hubs. Together, our findings suggest that promoter-enhancer hubs are dynamic and heterogeneous topological assemblies, which are controlled by oncogenic transcription factors and facilitate subtype-restricted gene expression in cancer.

Doxorubicin downregulates cell cycle regulatory hub genes in breast cancer cells.

Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.

Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

Global Study on the Accuracy of Human Epidermal Growth Factor Receptor 2-Low Diagnosis in Breast Cancer.

Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+/2+ with no gene amplification. To assess pathologists' accuracy and training efficacy in the diagnosis of HER2-low. Agreement rates of HER2-low scoring in breast cancer tissue were assessed between expert consensus and real-world pathologists (n = 77 from 14 countries) before and after a specific 4-hour training for HER2-low detection. Two assays were evaluated, the Ventana Pathway 4B5 CDx and the Dako HercepTest (polyclonal). Concordance of the pathologists with consensus score and efficacy of training were measured by Cohen κ, overall rater agreement, and receiver operating characteristic (ROC) curve statistics. In the Ventana 4B5 HER2-low category, baseline agreement rates were >80% but <90%. Negative percentage agreement was improved from 80.6% to 91.1% by training. In the HER2-0 category, positive percentage agreement (74.6%) was the only parameter below the 80% benchmark but was significantly improved to 89.2% after training. Training efficacy was confirmed by ROC curve analysis, which shows improvement for the identification of HER2-0 and HER2-low cases. Finally, in-depth examination of cases with discordant HER2 status disclosed specific issues of HER2-low underscoring and overscoring. The ability of pathologists to achieve acceptable diagnostic accuracy in identifying patients with HER2-low breast cancer could be enhanced by short-term training. Potential routes to improve the quality of HER2-low scoring in clinical practice have been identified.

Sociodemographic and clinical characteristics associated with rehabilitation services utilization in older women with early-stage breast cancer from SEER-Medicare 2009-2018.

Rehabilitation services are recommended by clinical practice guidelines following breast cancer treatment, yet little is known about how utilization may vary by patient-level characteristics which we aimed to study using SEER-Medicare data. Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was used to identify non-metastatic breast cancer survivors aged ≥ 66years diagnosed between 2011 and 2016. Rehabilitation services delivered 0-11months post-diagnosis were identified via outpatient or physician visit claims. Descriptive statistics and associations between patient characteristics and rehabilitation services were calculated using modified Poisson models estimating relative risk (RR) and corresponding 95% confidence intervals (CIs). Of 55,539 breast cancer survivors, 33% (n = 18,244) had received any type of rehabilitative services. Survivors were a mean age of 75years (SD 6.7), 88% White, 86% urban-dwelling, and 21% Medicare/Medicaid dually enrolled. In adjusted models, patients aged > 75 vs. ≤ 75 were 6% (RR 0.94, 95% CI 0.92-0.96) less likely to have received rehabilitative services. Survivors in an area with greater educational attainment vs. less educational attainment, White vs. non-White, or living in a rural vs. urban area were 26% (1.26, CI 1.22-1.30), 6% (1.06, CI 1.02-1.11), and 6% (1.06, CI 1.02-1.10) more likely to have received rehabilitative services, respectively. The largest differences in rehabilitation utilization were observed for survivors of differing educational and treatment statuses. Further research is needed on barriers, access, and delivery of rehabilitation services, specifically for breast cancer survivors who are older-aged, non-White, or Medicare/Medicaid dual eligible.

Morin overcomes doxorubicin resistance in human breast cancer by inducing DNA damage and modulating the LKB1/AMPK/mTORC1 signaling pathway.

Breast cancer chemoresistance hampers chemotherapy efficacy; researchers investigate the pharmacological activities of natural products for potential solutions. This study aimed to determine the effect of morin, a bioflavonoid isolated from Maclura pomifera, on two Dox-resistant human breast cancer cell lines MDA-MB-231 (MDA-DR) and MCF-7 (MCF-DR). Sulforhodamine B and colony-forming assays demonstrated the cytotoxic effect of morin on both cell lines. Morin induced DNA damage and reduced the DNA repair mechanism, a feature of chemoresistance. In addition, morin reduced the protein expressions of cell cycle regulators, such as cyclin D1, CDK4, cyclin E1, cyclin B1, and p-Rb, thereby halting cell cycle progression. Moreover, morin slightly reduced PARP and Bcl-xL expressions but left LC3-II and RIPK3 expressions unchanged. Annexin-V/7-AAD analysis showed morin increased 7-AAD positive cells and annexin-V positive cells among MDA-DR and MCF-DR cells, respectively. In addition, morin increased p-AMPK and p-LKB1 levels; and, thus, inhibited phosphorylation of the mTOR pathway, but decreased t-AMPK levels by inducing lysosomal degradation, and AICAR, an AMPK activator, reduced Raptor, cyclin D1, CDK4, cyclin E1 and phosphorylated, and total mTOR levels, indicating AMPK is a key player in inducing cell death. Also, morin modulated MAPK phosphorylation and attenuated p-Akt and p-GSK3αβ levels; and thus, inhibited cell survival. In addition, morin suppressed tumor growth in our MDA-DR xenografted mouse model. These findings indicate that morin is a potential treatment for Dox-resistant breast cancer and that it does so by inducing DNA damage and modulating the LKB1/AMPK/mTORC1 pathway, along with regulating the MAPK, and Akt/GSK3αβ signaling pathways.

Quantitative Three-Dimensional Imaging Analysis of HfO2 Nanoparticles in Single Cells via Deep Learning Aided X-ray Nano-Computed Tomography.

It is crucial for understanding mechanisms of drug action to quantify the three-dimensional (3D) drug distribution within a single cell at nanoscale resolution. Yet it remains a great challenge due to limited lateral resolution, detection sensitivities, and reconstruction problems. The preferable method is using X-ray nano-computed tomography (Nano-CT) to observe and analyze drug distribution within cells, but it is time-consuming, requiring specialized expertise, and often subjective, particularly with ultrasmall metal nanoparticles (NPs). Furthermore, the accuracy of batch data analysis through conventional processing methods remains uncertain. In this study, we used radioenhancer ultrasmall HfO2 nanoparticles as a model to develop a modular and automated deep learning aided Nano-CT method for the localization quantitative analysis of ultrasmall metal NPs uptake in cancer cells. We have established an ultrasmall objects segmentation method for 3D Nano-CT images in single cells, which can highly sensitively analyze minute NPs and even ultrasmall NPs in single cells. We also constructed a localization quantitative analysis method, which may accurately segment the intracellularly bioavailable particles from those of the extracellular space and intracellular components and NPs. The high bioavailability of HfO2 NPs in tumor cells from deeper penetration in tumor tissue and higher tumor intracellular uptake provide mechanistic insight into HfO2 NPs as advanced radioenhancers in the combination of quantitative subcellular image analysis with the therapeutic effects of NPs on 3D tumor spheroids and breast cancer. Our findings unveil the substantial uptake rate and subcellular quantification of HfO2 NPs by the human breast cancer cell line (MCF-7). This revelation explicates the notable efficacy and safety profile of HfO2 NPs in tumor treatment. These findings demonstrate that this 3D imaging technique promoted by the deep learning algorithm has the potential to provide localization quantitative information about the 3D distributions of specific molecules at the nanoscale level. This study provides an approach for exploring the subcellular quantitative analysis of NPs in single cells, offering a valuable quantitative imaging tool for minute amounts or ultrasmall NPs.

Abemaciclib for treating patients with HR+/HER2- metastatic breast cancer: a real-world study in France, Italy and Spain.

Aim: This real-world study aimed to describe patient and clinical characteristics, treatment patterns and outcomes for patients with HR+/HER2-metastatic breast cancer receiving abemaciclib in France, Italy and Spain. Materials & methods: A multicenter chart review was conducted for adult females with HR+/HER2- advanced/metastatic breast cancer who received abemaciclib in routine care. Real-world progression-free survival (rwPFS) was estimated via Kaplan-Meier curves. Results: This study included 151, 173 and 175 patients from France, Italy and Spain, respectively. Abemaciclib was mostly prescribed as first-line therapy concomitantly with hormone therapy. Median rwPFS was >20months and the 1-year rwPFS rate was >70%. Conclusion: Effectiveness was similar across the three countries and aligns with pivotal studies.