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Most often, aberrant cell proliferation and subsequent tumour formation are the causes of cancer development. Globally, millions of people are estimated to die from various types of cancer. Among various types of cancer, breast cancer is the most prevalent type in women throughout the world. It continues to have a high death rate even with different treatment approaches. Because of the complex natural etiology of breast cancer, its treatment is much challenging. Owing to substantial treatment hurdles, natural chemicals are being investigated as possible substitutes. The plant Azadirachta indica (L.); is extensively recognised since ancient times for various therapeutic uses in Ayurveda, Unani, and homeopathic medicine system. Scientifically, the phytoremedial compounds and anticancer properties of this plant have been widely studied in term of its preventive, protective, tumour-suppressive, immunomodulatory, and apoptotic actions against different cancers and their molecular processes. The present study focuses on therapeutic effect of Azadirachta indica (L.) flowers ethanolic extract (AIEE) against DMBA induced breast cancer in Swiss albino mice. Eighteen female mice weighing 30 ± 5 g were divided into two groups. Group-I: control (n=6) and Group-II: (n=12); were orally induced by DMBA (3 mg/ml dissolved in olive oil) at an interval of fourteen days until breast tumours (about 2.0 cm) were developed. Then after, Group-II was further divided into two sub-groups. Sub-Group-I; (n=6) as DMBA-Treated were sacrificed at same time and sub-group-II (n=6) were orally administered with AIEE (100mg/Kg body weight) for 5 weeks, and the last tumour volume were measured. The study results that, the mammary tumour volume significantly (p<0.05) reduced. Moreover, there was significant alteration (p<0.0001) observed at the level of hepatic and renal biomarkers. Conclusively, entire study depicts that AIEE administration possesses anti-proliferative activity by suppressing progression of breast tumour in mice model. AIEE administration also possesses significant (p<0.0001) improvement in the hepato-renal parameters. Therefore, Azadirachta indica flowers can be targeted as a novel and safe anti-cancer drug against breast cancer. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains a significant global health challenge. Understanding its etiological factors, particularly the role of immune system components, is crucial. This study leverages Mendelian randomization (MR) to investigate the causal relationship between various immune cell features and the risk of developing breast cancer. Methods: Utilizing two-sample MR analysis, we examined 731 immune cell features across 7 groups for their potential causal links to breast cancer. We analyzed genome-wide association studies (GWAS) data of 257,730 Europeans, comprising 17,389 cases and 240,341 controls, focusing on 24,133,589 single nucleotide polymorphisms (SNPs). Instrumental variables (IVs) were selected based on genetic associations, with rigorous statistical methods employed, including inverse variance weighting (IVW) and weighted median-based estimation. Results: Our analysis identified 20 immunophenotypes with significant causal associations with breast cancer risk. Notably, contain B cell, mature T cell, T + B + NK (TBNK) cells, regulatory T (Treg) cell, Classic dendritic cells (cDCs), Monocyte, and Myeloid cell group features displayed positive or negative correlations with breast cancer. For instance, specific B cell phenotypes were found to have both positive and negative causal relationships with breast cancer. Additionally, reverse MR analysis revealed no significant causal effects of breast cancer on these immune characteristics. Conclusions: This study underscores the complex interplay between various immune cell phenotypes and breast cancer risk. The identified immunophenotypes could be potential biomarkers or targets for future therapeutic interventions. Our findings contribute to a deeper understanding of the immunological dimensions of breast cancer etiology. [ABSTRACT FROM AUTHOR]

Purpose: We prospectively analyzed the correlation between fasting plasma glucose (FPG) and the risk of breast cancer in women; explored the independent risk factors for breast cancer in women, and compared the effect of FPG level on the risk of young and non-young breast cancer. Our study provides new evidence and ideas for research into breast cancer etiology in China, improves the accuracy of secondary prevention of breast cancer, and provides options for the clinical diagnosis and treatment of breast cancer patients with diabetes. Materials and methods: Three cohorts of women participating in the first health examination of the Kailuan Group in 2006, 2008 and 2010 were assembled to conduct a descriptive analysis of the baseline data on FPG. The cumulative incidence of breast cancer in different groups over 13 years was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A Cox proportional hazards regression model was used to analyze the association between FPG level and the risk of breast cancer. Results: The cumulative incidence of breast cancer increased in people with FPG higher than 5.29 mmol/L, but there was no significant difference in the effect of different levels of FPG on the risk of young breast cancer in the population. Different degrees of fasting glucose can affect the risk of non-young breast cancer in the population. Conclusion: The results of this study suggest that the risk of breast cancer can be reversed by early intervention to control levels of FPG. Regular monitoring of FPG may reduce the misdiagnosis rate of breast cancer in the population. [ABSTRACT FROM AUTHOR]

Splicing-based transcriptome-wide association studies (splicing-TWASs) of breast cancer have the potential to identify susceptibility genes. However, existing splicing-TWASs test the association of individual excised introns in breast tissue only and thus have limited power to detect susceptibility genes. In this study, we performed a multi-tissue joint splicing-TWAS that integrated splicing-TWAS signals of multiple excised introns in each gene across 11 tissues that are potentially relevant to breast cancer risk. We utilized summary statistics from a meta-analysis that combined genome-wide association study (GWAS) results of 424,650 women of European ancestry. Splicing-level prediction models were trained in GTEx (v.8) data. We identified 240 genes by the multi-tissue joint splicing-TWAS at the Bonferroni-corrected significance level; in the tissue-specific splicing-TWAS that combined TWAS signals of excised introns in genes in breast tissue only, we identified nine additional significant genes. Of these 249 genes, 88 genes in 62 loci have not been reported by previous TWASs, and 17 genes in seven loci are at least 1 Mb away from published GWAS index variants. By comparing the results of our splicing-TWASs with previous gene-expression-based TWASs that used the same summary statistics and expression prediction models trained in the same reference panel, we found that 110 genes in 70 loci that are identified only by the splicing-TWASs. Our results showed that for many genes, expression quantitative trait loci (eQTL) did not show a significant impact on breast cancer risk, whereas splicing quantitative trait loci (sQTL) showed a strong impact through intron excision events. Investigating alternative splicing could provide new insight into the genetic etiology of breast cancer. By a multi-tissue, joint splicing-based transcriptome-wide association study (TWAS) that integrates signals of multiple excised introns in a gene, the authors identified 88 breast cancer susceptibility genes that have not been reported in previous TWASs. [ABSTRACT FROM AUTHOR]

Background: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. Methods: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. Results: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. Conclusions: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women. [ABSTRACT FROM AUTHOR]

This article explores the role of progesterone in breast cancer, emphasizing the distinction between causing breast cancer and stimulating its growth. The authors highlight the mutagenicity of progesterone and its ability to stimulate the synthesis of mutagens in normal breast cells. They also discuss the relationship between menstrual cycles, reproductive hormones, and breast cancer occurrence. The article suggests that hormonal contraception and menopausal hormone therapy do not significantly increase breast cancer risk, but long-term use of progestogen-only contraception may have a higher risk. The protective effect of pregnancy on breast cancer is also discussed, as well as the lag time between a mutation and breast cancer diagnosis. The authors propose further research to fully understand the relationship between progesterone and breast cancer. [Extracted from the article]

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies. [ABSTRACT FROM AUTHOR]

Globally, breast cancer is not only the most frequently diagnosed cancer but also the leading cause of cancer death in women. Depending on breast cancer histotype, conventional breast cancer treatment options vary greatly in efficacy and accompanying side effects. Thus, there is a need for more effective and safer strategies that impact breast cancer at all stages. Plant-based natural products are easily available, with them proving effective and inexpensive. Two such phytochemicals are chlorogenic acid and cinnamaldehyde. Studies have shown their efficacy against different molecular subtypes of breast cancers in vitro and in vivo. In this review, we discuss their current status in anticancer research with specific emphasis on chlorogenic acid and cinnamaldehyde. We describe their multiple mechanisms of action in destroying breast cancer cells, their potential uses, and the need for translational applications. We also include future directions for investigations to progress chlorogenic acid and cinnamaldehyde research from bench to bedside. [ABSTRACT FROM AUTHOR]

Cancer etiology represents an intricate, multifactorial orchestration where metabolically associated insulin-like growth factors (IGFs) and insulin foster cellular proliferation and growth throughout tumorigenesis. The insulin receptor (IR) exhibits two splice variants arising from alternative mRNA processing, namely IR-A, and IR-B, with remarkable distribution and biological effects disparities. This insightful review elucidates the structural intricacies, widespread distribution, and functional significance of IR-A and IR-B. Additionally, it explores the regulatory mechanisms governing alternative splicing processes, intricate signal transduction pathways, and the intricate association linking IR-A and IR-B splicing variants to breast and prostate cancer tumorigenesis. Breast cancer and prostate cancer are the most common malignant tumors with the highest incidence rates among women and men, respectively. These findings provide a promising theoretical framework for advancing preventive strategies, diagnostic modalities, and therapeutic interventions targeting breast and prostate cancer. [ABSTRACT FROM AUTHOR]

Observational studies showed that metabolic phenotypes were associated with the risk of developing breast cancer (BC). However, those results are inconsistent regarding the magnitude of the association, particularly by subtypes of breast cancer. Furthermore, the mechanisms of the association remain unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of metabolic risk factors on breast cancer in the European population. Assessed individually using MR, body mass index (BMI) (odds ratio [OR] 0.94, 95% Confidence interval [CI] 0.90–0.98, P = 0.007), high-density lipoprotein cholesterol (HDL-C) (OR 1.10, 95% CI 1.07–1.13, P = 6.10 × 10–11) and triglycerides (TG) (OR 0.92, 95% CI 0.90–0.96, P = 1.58 × 10–6) were causally related to breast cancer risk. In multivariable MR, only HDL-C (OR 1.08; 95% CI 1.02–1.14; P = 0.02) retained a robust effect, suggesting that the genetic association between BMI, HDL-C and TG with breast cancer risk in univariable analysis was explained via HDL-C. These findings suggest a possible causal role of HDL-C in breast cancer etiology. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Approximately 50% of breast cancers are discovered at an early stage in patients for whom conservative surgery is indicated. Intraoperative localization of non-palpable breast lesions is generally accomplished using a hook wire to mark the area of concern under ultrasound or stereotactic localization. But this technique has several drawbacks (painful, stressful...). We propose the use of a wire-free breast lesion system using miniature radiofrequency identification (RFID) tags. This technique could improve patient comfort and surgical comfort for surgeons. We therefore propose a study to assess the interest of introducing the RFID localization technique at the Jean PERRIN comprehensive cancer center. Methods: This is a single-center prospective trial designed to assess the interest in introducing the RFID localization technique at the Jean Perrin center. It aims to show the superiority of the RFID technique in terms of patient tolerance compared to the gold-standard (hook wire). A sequential inclusion in time will be performed: 20 inclusions in the gold-standard group, then 20 patients in the RFID group before repeating the inclusion scheme. Any patient requiring preoperative localization will receive a senology consultation. The RFID tag will be placed during this consultation. The hook wire localization will be done the day before the surgery. Patients will fill out a Hospital Anxiety and Depression scale (HAD) questionnaire at the time of inclusion. They will then fill out a satisfaction questionnaire in 2 steps: during the placement of the device (RFID tag or hook wire) or during the postoperative consultation at 1 month. Radiologists and surgeons will fill out a questionnaire to evaluate the localization technique, respectively after the localization and surgery procedures. Discussion: The RFID study is the first study in France which specifically assesses the interest of the RFID localization in terms of patients comfort. Patient comfort is one of the key elements to take into consideration when managing patients in oncology and new technologies such as RFID tags could improve it. Trial registration: ClinicalTrials.gov ID; NCT04750889 registered on February 11, 2021. [ABSTRACT FROM AUTHOR]

Breast cancer is a fusion, diverse, and composite disease of women. There is no sole cause of breast cancer. The Origin of breast cancer are not perfectly known. However, there are many predisposing factors known to affect possibility of developing breast cancer. The risk of breast cancer has been compatible associated with age, a family or genetically history of breast cancer, History of early menarche, Delayed age first pregnancy, short period or no breastfeeding, and late menopause, Prolonged period of hormonal therapy (HT), alcohol consumption, sedentary lifestyle, exposure to ionizing radiation like X-rays, and genetic predisposition. Mutations in inherited high penetrance genes can cause only 5-10% of all types of breast cancers. [ABSTRACT FROM AUTHOR]

Many factors, including reproductive hormones, have been linked to a woman's risk of developing breast cancer (BC). We reviewed the literature regarding the relationship between ovulatory menstrual cycles (MCs) and BC risk. Physiological variations in the frequency of MCs and interference with MCs through genetic variations, pathological conditions and or pharmaceutical interventions revealed a strong link between BC risk and the lifetime number of MCs. A substantial reduction in BC risk is observed in situations without MCs. In genetic or transgender situations with normal female breasts and estrogens, but no progesterone (P4), the incidence of BC is very low, suggesting an essential role of P4. During the MC, P4 has a strong proliferative effect on normal breast epithelium, whereas estradiol (E2) has only a minimal effect. The origin of BC has been strongly linked to proliferation associated DNA replication errors, and the repeated stimulation of the breast epithelium by P4 with each MC is likely to impact the epithelial mutational burden. Long-lived cells, such as stem cells, present in the breast epithelium, can carry mutations forward for an extended period of time, and studies show that breast tumors tend to take decades to develop before detection. We therefore postulate that P4 is an important factor in a woman's lifetime risk of developing BC, and that breast tumors arising during hormonal contraception or after menopause, with or without menopausal hormone therapy, are the consequence of the outgrowth of pre-existing neoplastic lesions, eventually stimulated by estrogens and some progestins. [ABSTRACT FROM AUTHOR]

Background: Complex systems models of breast cancer have previously focused on prediction of prognosis and clinical events for individual women. There is a need for understanding breast cancer at the population level for public health decision-making, for identifying gaps in epidemiologic knowledge and for the education of the public as to the complexity of this most common of cancers. Methods and findings: We developed an agent-based model of breast cancer for the women of the state of California using data from the U.S. Census, the California Health Interview Survey, the California Cancer Registry, the National Health and Nutrition Examination Survey and the literature. The model was implemented in the Julia programming language and R computing environment. The Paradigm II model development followed a transdisciplinary process with expertise from multiple relevant disciplinary experts from genetics to epidemiology and sociology with the goal of exploring both upstream determinants at the population level and pathophysiologic etiologic factors at the biologic level. The resulting model reproduces in a reasonable manner the overall age-specific incidence curve for the years 2008–2012 and incidence and relative risks due to specific risk factors such as BRCA1, polygenic risk, alcohol consumption, hormone therapy, breastfeeding, oral contraceptive use and scenarios for environmental toxin exposures. Conclusions: The Paradigm II model illustrates the role of multiple etiologic factors in breast cancer from domains of biology, behavior and the environment. The value of the model is in providing a virtual laboratory to evaluate a wide range of potential interventions into the social, environmental and behavioral determinants of breast cancer at the population level. [ABSTRACT FROM AUTHOR]

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancerspecific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immuneassociated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes. [ABSTRACT FROM AUTHOR]

The number of breast cancer incidences reported worldwide has increased tremendously over the years. Scoping down to Asia, in 2020, the reported incidences of breast cancer are appalling, comprising 1,026,171 cases, occupying up to 45.4% of cases across the globe. Breast cancer is a non-communicable disease, that emerges in variegated forms, self-subsistent, and the etiology is observed to be multifactorial, dependent on the individual reproductive pattern, hormonal factors, diet, physical activity, lifestyle, and exposure to certain advent procedures. Given this complexity, breast cancer is expected to undergo a persistent increment in the number of incidences in near future, exacerbating the public health quality, regardless of race, ethnicity, geographical subgroups, and socioeconomic. In this review article, the authors examine breast cancer in multiple facets, comprising the updated statistics on breast cancer, typically in Asia; etiology of breast cancer; diagnosis of breast cancer; grading system; and challenges in breast cancer from the country's income perspective. Realizing the ever-increasing demand for quality treatment, here, the article also contemplates common therapies in breast cancer, such as breast-conserving therapy, mastectomy, postmastectomy radiation therapy, neoadjuvant chemotherapy, axillary surgery, chemotherapy, adjuvant medical therapies, biological and targeted therapies, and endocrine therapy. This review article intended to provide a brief yet broad panoramic view of breast cancer, to readers, ranging from newcomers, existing researchers, and relevant stakeholders in the topic of interest. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. Surgery, radiotherapy, and chemotherapy are the main treatments for BC, even though the latter are often not aways successful because of the common side effects and the damage caused to healthy tissues and organs. Aggressive and metastatic BCs are difficult to treat, thus new studies are needed in order to find new therapies and strategies for managing these diseases. In this review, we intend to give an overview of studies in this field, presenting the data from the literature concerning the classification of BCs and the drugs used in therapy for the treatment of BCs, along with drugs in clinical studies. [ABSTRACT FROM AUTHOR]

In women, breast cancer (BC) is the second most frequently diagnosed cancer and the leading cause of cancer death. Mesenchymal stem cells (MSCs) are a subgroup of heterogeneous non-hematopoietic fibroblast-like cells that have the ability to differentiate into multiple cell types. Recent studies stated that MSCs can migrate into the tumor sites and exert various effect on tumor growth and development. Multiple researches have demonstrated that MSCs can favor tumor growth, while other groups have indicated that MSCs inhibit tumor development. Emerging evidences showed exosomes (Exo) as a new mechanism of cell communication which are essential for the crosstalk between MSCs and BC cells. MSC-derived Exo (MSCs-Exo) could mimic the numerous effects on the proliferation, metastasis, and drug response through carrying a wide scale of molecules, such as proteins, lipids, messenger RNAs, and microRNAs to BC cells. Consequently, in the present literature, we summarized the biogenesis and cargo of Exo and reviewed the role of MSCs-Exo in development of BC. [ABSTRACT FROM AUTHOR]

Background: Breast cancer incidence rates have not declined despite an improvement in risk prediction and the identification of modifiable risk factors, suggesting the need to identify novel risk factors and etiological pathways involved in this cancer. Metabolomics has emerged as a promising tool to find circulating metabolites associated with breast cancer risk. Methods: Untargeted metabolomic analysis was done on prediagnostic plasma samples from a case–cohort study of 1695 incident breast cancer cases and a 1983 women subcohort drawn from Cancer Prevention Study 3. The associations of 868 named metabolites (per one standard deviation increase) with breast cancer were determined using Prentice-weighted Cox proportional hazards regression modeling. Results: A total of 11 metabolites were associated with breast cancer at false discovery rate (FDR) < 0.05 with the majority having inverse association [ranging from RR = 0.85 (95% CI 0.80–0.92) to RR = 0.88 (95% CI 0.82–0.94)] and one having a positive association [RR = 1.14 (95% CI 1.06–1.23)]. An additional 50 metabolites were associated at FDR < 0.20 with inverse associations ranging from RR = 0.88 (95% CI 0.81–0.94) to RR = 0.91 (95% CI 0.85–0.98) and positive associations ranging from RR = 1.13 (95% CI 1.05–1.22) to RR = 1.11 (95% CI 1.02–1.20). Several of these associations validated the findings of previous metabolomic studies. These included findings that several progestogen and androgen steroids were associated with increased risk of breast cancer in postmenopausal women and four phospholipids, and the amino acids glutamine and asparagine were associated with decreased risk of this cancer in pre- and postmenopausal women. Several novel associations were also identified, including a positive association for syringol sulfate, a biomarker for smoked meat, and 3-methylcatechol sulfate and 3-hydroxypyridine glucuronide, which are metabolites of xenobiotics used for the production of pesticides and other products. Conclusions: Our study validated previous metabolite findings and identified novel metabolites associated with breast cancer risk, demonstrating the utility of large metabolomic studies to provide new leads for understanding breast cancer etiology. Our novel findings suggest that consumption of smoked meats and exposure to catechol and pyridine should be investigated as potential risk factors for breast cancer. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is dynamically involved in many aspects of cell growth and survival, and it plays an active role in cancer etiology. In comparison to healthy ECM, tumor associated ECM shows high collagen deposition and remodeling activity, which results in an increased amount of denatured collagen strands in tumor tissues. Capitalizing on this distinguishing feature, we developed tumor-localizing polymeric carriers that selectively bind to denatured collagen in the tumor ECM. We synthesized N -(2-hydroxypropyl)methacrylamide (HPMA) copolymers with their side chains conjugated to collagen hybridizing peptides (CHPs). HPMA copolymer-CHP conjugates exhibited selective affinity to denatured collagen and localized to tumors in an orthotopic MDA-MB-231 murine breast cancer model. The conjugates had increased tumor localization compared to copolymers with scrambled peptides in the side chains, as well as increased retention compared to free CHPs. Such conjugates show promise as carriers for ECM-acting drugs and imaging agents in the management of diseases characterized by high ECM remodeling activity. [Display omitted] • Collagen-targeted polymers show advantage over non-targeted polymers and peptides. • Collagen hybridizing peptide improves tumor accumulation of water soluble polymers. • Targeting denatured collagen in the extracellular matrix facilitates tumor delivery. [ABSTRACT FROM AUTHOR]

Detection of breast mass plays a very important role in making the diagnosis of breast cancer. For faster detection of breast cancer caused by breast mass, we developed a novel and efficient patch-based breast mass detection system for mammography images. The proposed framework is comprised of three modules, including pre-processing, multiple-level breast tissue segmentation, and final breast mass detection. An improved Deeplabv3+ model for pectoral muscle removal is deployed in pre-processing. We then proposed a multiple-level thresholding segmentation method to segment breast mass and obtained the connected components (ConCs), where the corresponding image patch to each ConC is extracted for mass detection. In the final detection stage, each image patch is classified into breast mass and breast tissue background by trained deep learning models. The patches that are classified as breast mass are then taken as the candidates for breast mass. To reduce the false positive rate in the detection results, we applied the non-maximum suppression algorithm to combine the overlapped detection results. Once an image patch is considered a breast mass, the accurate detection result can then be retrieved from the corresponding ConC in the segmented images. Moreover, a coarse segmentation result can be simultaneously retrieved after detection. Compared to the state-of-the-art methods, the proposed method achieved comparable performance. On CBIS-DDSM, the proposed method achieved a detection sensitivity of 0.87 at 2.86 FPI (False Positive rate per Image), while the sensitivity reached 0.96 on INbreast with an FPI of only 1.29. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common women cancer and cause of cancer death. Despite decades of scientific progress in BC treatments, the clinical benefit of new drugs is modest in several cases. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway mutations are frequent in BC (20–40%) and are significant causes of aggressive tumor behavior, as well as treatment resistance. Improving knowledge of the PI3K/AKT/mTOR pathway is an urgent need. This review aims to highlight the central role of PI3K-mTORC1/C2 mutations in the different BC subtypes, in terms of clinical outcomes and treatment efficacy. The broad base of knowledge in tumor biology is a key point for personalized BC therapy in the precision medicine era. [ABSTRACT FROM AUTHOR]

Asymmetric cell division is a key tumor suppressor mechanism that prevents the uncontrolled expansion of the stem cell (SC) compartment by generating daughter cells with alternative fates: one retains SC identity and enters quiescence and the other becomes a rapidly proliferating and differentiating progenitor. A critical player in this process is Numb, which partitions asymmetrically at SC mitosis and inflicts different proliferative and differentiative fates in the two daughters. Here, we show that asymmetric Numb partitioning per se is insufficient for the proper control of mammary SC dynamics, with differential phosphorylation and functional inactivation of Numb in the two progeny also required. The asymmetric phosphorylation/inactivation of Numb in the progenitor is mediated by the atypical PKCζ isoform. This mechanism is subverted in breast cancer via aberrant activation of PKCs that phosphorylate Numb in both progenies, leading to symmetric division and expansion of the cancer SC compartment, associated with aggressive disease. Thus, Numb phosphorylation represents a target for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Female cancers, especially breast, ovarian, cervical, and endometrial cancers, constitute a major threat to women's health worldwide. In view of the complex genetic background of cancers cannot be fully explained with current genetic information, we used a bidirectional two-sample mendelian randomization approach to explore the causal associations between serum metabolites and four major female cancers—breast, ovarian, cervical, and endometrial cancers. We analyzed the metabolites dataset from the Canadian Longitudinal Study of Aging and cancer datasets from the 10th round of the Finngen project. Replication analyses was performed with Cancer Association Consortium and Leo's studies. Instrumental variables were analyzed using methods including the Wald ratio, inverse-variance weighted, MR-Egger, and weighted median. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out methods. After meticulous analysis, we obtained levels of 3-hydroxyoleoylcarnitine, hexadecanedioate, tetradecanedioate, and carnitine C14 with robust causal associations with breast cancer, levels of 5alpha-androstan-3alpha,17beta-diol monosulfate (1), androstenediol (3beta,17beta) monosulfate (1), androsterone sulfate, and 5alpha-androstan-3beta,17beta-diol disulfate causal associations with endometrial cancer. The reverse analysis showed that breast, ovarian, and endometrial cancer and survival of breast and ovarian cancer were found to have causal relationships with 8, 5, 2, 6, and 3 metabolites, respectively. These insights underscore the potential roles of specific metabolites in the etiology of female cancers, providing new biomarkers for early detection, risk stratification, and disease progression monitoring. Further research could elucidate how these metabolites influence specific pathways in cancer development, offering theoretical foundations for prevention and treatment strategies. [Display omitted] • Bidirectional mendelian randomization was used to explore key metabolites influencing female cancer risks. • Discovered Serum metabolites like carnitine C14 as indicators for early cancer detection and monitoring. • Some metabolites like methionine exhibit deteriorating or protective effects on cancer prognosis. [ABSTRACT FROM AUTHOR]

Currently, breast cancer appears to be the most widespread cancer in the world and the most common cause of cancer deaths. This specific type of cancer affects women in both developed and developing countries. Prevention and early diagnosis are very important factors for good prognosis. A characteristic feature of cancer cells is the ability of unlimited cell division, which makes them immortal. Telomeres, which are shortened with each cell division in normal cells, are rebuilt in cancer cells by the enzyme telomerase, which is expressed in more than 85% of cancers (up to 100% of adenocarcinomas, including breast cancer). Telomerase may have different functions that are related to telomeres or unrelated. It has been shown that high activity of the enzyme in cancer cells is associated with poor cell sensitivity to therapies. Therefore, telomerase has become a potential target for cancer therapies. The low efficacy of therapies has resulted in the search for new combined and more effective therapeutic methods, including the involvement of telomerase inhibitors and telomerase-targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Estrogen (E2) is crucial for the development of breast cancer caused by BRCA1 mutation, and can increase the DNA damage in BRCA1-deficient cells. However, the mechanisms through which BRCA1 deficiency and E2 synergistically induce DNA damage remains unclear. In this study, we analyzed the distribution of DNA damage in E2-treated BRCA1-deficient cells. We detected DNA lesions in the vicinity of genes that are transcriptionally activated by estrogen receptor-α (ER). Loss of BRCA1 altered chromatin binding by ER, which significantly affected the distribution of DNA damage. Moreover, these changes were associated with the established mutations in BRCA1-mutant breast cancer. Taken together, our findings reveal a new mechanism underlying the DNA damage in breast cancer cells that is synergistically induced by BRCA1 deficiency and E2. [Display omitted] • BRCA1 deficiency increased ER binding on specific genome region where tends to occur DNA damage. • DNA damages accumulate at the genes transcriptionally activated by ER. • DNA damage synergistically induced by BRCA1 deficiency and E2 is associated with clinical mutations. [ABSTRACT FROM AUTHOR]

Estrogen hormone is one of the steroid hormones has a critical role in breast cancer etiology. It has been implicated in proliferation and differentiation of cells through its action promoting binding of its receptor to DNA, changing transcriptional expression of target genes. In addition to the classical DNA binding mechanism, estrogen can also regulate gene expression through a no genomic mechanism associated with activation a variety of signal transduction pathways (e.g. PI3`K/AKT, ERK/MAPK, PLC/PKCs, p38/MAPK). Dysregulation of the balance between pro-apoptotic and anti-apoptotic members of the Bcl-2 family, would result in apoptosis inhibition and tumor genesis (Chimento et al., 2022). Also, poor responses towards hormonal therapy, radiotherapy, and chemotherapy and treatment resistance are likely caused by dysregulation of apoptosis. Importantly, E2 has been shown to prevent apoptosis, first through its action in activation of anti-apoptotic proteins like Bcl-xl and Bcl-2 in breast cells like MCF-7, T47D and ZR-75-1 or due to its metabolites independently of ER. Estrogen metabolism includes several very important pathways that can possibly induce de novo DNA mutation. These pathways include:2, &4-hydroxylation, 16 α hydroxylation and 4 hydroxyestradiol-quinone-adenine/guanine adduct depurination, which subsequently participate in DNA damage that can lead to breast cancer. Endocrine resistance is considered one of the most permanent problems that can reduce the benefits of breast cancer treatment. Alteration of microRNAs expression, polymorphisms occurring in tamoxifen metabolism, and using redundant alternative signaling pathways, resulting in poor treatment responses of breast cancer patients and induction of endocrine resistance. Thus, most proposed therapeutic strategies will be based on a combination of drugs targeting various pathways alongside endocrine therapy that may improve the outcomes of endocrine responses in resistant breast cancer cells. [ABSTRACT FROM AUTHOR]

Breast cancer causes numerous deaths worldwide; yet the numbers have decreased in the past years as a result of computer-aided diagnosis and proper treatment. The current paper is addressed to the base of such diagnosis system: pre-processing and segmentation. After a robust pre-processing, an unsupervised version of GrowCut is applied to define the location of the abnormality. We present a method to automatically define the foreground seeds used in GrowCut. For experiments, mammograms from mini-MIAS dataset are used and a precision of 93.63% for the foreground seeds masks is achieved, which leads to promising segmentation results. [ABSTRACT FROM AUTHOR]

Background: Occupational exposures may play a role in breast cancer etiology, and research focusing on identifying high‐risk workplaces is important to advance the understanding and prevention of breast cancer. Methods: We undertook a population‐based nested case–control study among women who were less than 70 years of age and born in Denmark, based on registry data including 38,375 breast cancer cases and 191,875 controls matched on year of birth, with information on lifetime work history. Odds ratios for women ever employed in a job branch were adjusted for socioeconomic status and reproductive variables. Results: Adjusted odds ratios of less than 0.75 were observed for several occupations in agriculture, hunting, forestry, and fishing, while increased risk patterns (odds ratios greater than 1.50) were noted for a number of production occupations, including employment in graphics and printing, and metal and machinery production. In services, several military professions were also associated with a high increased breast cancer risk. Conclusions: The study shows a variation in the risk of female breast cancer by employment in different industrial and occupational sectors, and suggests that certain occupational exposures, for example, outdoor work, organic solvents, polycyclic aromatic hydrocarbons (PAHs), and night‐shift work may play a role in the risk of breast cancer. Further hypothesis‐testing studies focusing on these employments with a detailed assessment of specific occupational exposures are warranted. [ABSTRACT FROM AUTHOR]

For de novo mutational signature analysis, the critical first step is to decide how many signatures should be expected in a cancer genomics study. An incorrect number could mislead downstream analyses. Here we present SUITOR (Selecting the nUmber of mutatIonal signaTures thrOugh cRoss-validation), an unsupervised cross-validation method that requires little assumptions and no numerical approximations to select the optimal number of signatures without overfitting the data. In vitro studies and in silico simulations demonstrated that SUITOR can correctly identify signatures, some of which were missed by other widely used methods. Applied to 2,540 whole-genome sequenced tumors across 22 cancer types, SUITOR selected signatures with the smallest prediction errors and almost all signatures of breast cancer selected by SUITOR were validated in an independent breast cancer study. SUITOR is a powerful tool to select the optimal number of mutational signatures, facilitating downstream analyses with etiological or therapeutic importance. Author summary: Mutational signatures are the footprints of exogenous exposures and endogenous mutational processes on the cancer genomes. To estimate de novo mutational signatures, the first step is to decide how many signatures should be extracted in a cancer genomics study, which determines downstream analytical steps and has been insufficiently studied. We developed SUITOR, an unsupervised cross-validation method to select the optimal number of signatures without overfitting the data. We demonstrated SUITOR's superior performance using in vitro experimental studies, in silico simulations and in vivo pan-cancer applications of 2,540 whole-genome sequenced tumors across 22 cancer types, and validated signatures of breast cancer in additional 440 breast tumors. SUITOR advances the methodological frontier of identifying de novo mutational signatures and would help discover the causes of cancer and the means of cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) makes up a majority of noninvasive breast cancer cases. DCIS is a neoplastic proliferation of epithelial cells within the ductal structure of the breast. Currently, there is little known about the progression of DCIS to invasive ductal carcinoma (IDC), or the molecular etiology behind each DCIS lesion or grade. The DCIS lesions can be heterogeneous in morphology, genetics, cellular biology, and clinical behavior, posing challenges to our understanding of the molecular mechanisms by which approximately half of all DCIS lesions progress to an invasive status. New strategies that pinpoint molecular mechanisms are necessary to overcome this gap in understanding, which is a barrier to more targeted therapy. In this review, we will discuss the etiological factors associated with DCIS, as well as the complexity of each nuclear grade lesion. Moreover, we will discuss the possible molecular features that lead to progression of DCIS to IDC. We will highlight current therapeutic management and areas for improvement. [ABSTRACT FROM AUTHOR]

Background: Secondhand smoke is an important risk factor to breast cancer patients' survival. This article aimed to describe the epidemiological changes of health loss caused by female breast cancer attributable to secondhand smoke from 1990 to 2019. Methods: Data on breast cancer was derived from the Global Burden of Disease study 2019. The epidemiological status and trends were estimated using the number, age-standardized rate (ASR), and estimated annual percentage change (EAPC). Results: In 2019, secondhand smoke-related breast cancer caused 168.33×102 death, 5242.58×102 years of life lost (YLLs), and 334.03×102 years lived with disability (YLDs) globally. The overall ASR of death and YLLs caused by breast cancer attributable to secondhand smoke presented decreasing trends from 1990 to 2019, with the respective EAPCs of −0.78 and −0.87. Meanwhile, decreasing trends occurred in most geographic regions, particularly that of YLLs in high-income North America (EAPC = −3.35). At the national level, most countries/territories had decreasing trends of death and YLLs, particularly Denmark, in which the respective EAPCs were −4.26 and −4.64. However, the ASR of YLDs showed an increasing trend globally (EAPC = 0.32). Meanwhile, increasing trends were observed in most regions and countries, particularly the Solomon Islands and Lesotho, with the respective EAPCs being 6.18 and 4.33. The changing trends were closely associated with sociodemographic development. Conclusions: Trends in secondhand smoke-related death and YLLs caused by breast cancer declined from 1990 to 2019. However, secondhand smoke remains a challenge to the patients' longevity and quality of life. The findings informed strategies should be strengthened the control of secondhand smoking. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of malignancy and leading cause of cancer death among women worldwide. Despite the current revolutionary advances in the field of cancer immunotherapy, clinical response in breast cancer is frequently below expectations, in part due to various mechanisms of cancer immune escape that produce tumor variants that are resistant to treatment. Thus, a further understanding of the molecular events underlying immune evasion in breast cancer may guarantee a significant improvement in the clinical success of immunotherapy. Furthermore, nanomedicine provides a promising opportunity to enhance the efficacy of cancer immunotherapy by improving the delivery, retention and release of immunostimulatory agents in targeted cells and tumor tissues. Hence, it can be used to overcome tumor immune escape and increase tumor rejection in numerous malignancies, including breast cancer. In this review, we summarize the current status and emerging trends in nanomedicine-based strategies targeting cancer immune evasion and modulating the immunosuppressive tumor microenvironment, including the inhibition of immunosuppressive cells in the tumor area, the activation of dendritic cells and the stimulation of the specific antitumor T-cell response. [ABSTRACT FROM AUTHOR]

Reproductive and hormonal factors may influence breast cancer risk via endogenous estrogen exposure. Cumulative menstrual months (CMM) can be used as a surrogate measure of this exposure. Using harmonized data from four population‐based breast cancer studies (7284 cases and 7242 controls), we examined ethnicity‐specific associations between CMM and breast cancer risk using logistic regression, adjusting for menopausal status and other risk factors. Higher CMM was associated with increased breast cancer risk in non‐Hispanic Whites, Hispanics and Asian Americans regardless of menopausal status (all FDR adjusted P trends =.0004), but not in African Americans. In premenopausal African Americans, there was a suggestive trend of lower risk with higher CMM. Stratification by body mass index (BMI) among premenopausal African American women showed a nonsignificant positive association with CMM in nonobese (BMI <30 kg/m2) women and a significant inverse association in obese women (OR per 50 CMM = 0.56, 95% CI 0.37‐0.87, Ptrend =.03). Risk patterns were similar for hormone receptor positive (HR+; ER+ or PR+) breast cancer; a positive association was found in all premenopausal and postmenopausal ethnic groups except in African Americans. HR− (ER− and PR−) breast cancer was not associated with CMM in all groups combined, except for a suggestive positive association among premenopausal Asian Americans (OR per 50 CMM = 1.33, P =.07). In summary, these results add to the accumulating evidence that established reproductive and hormonal factors impact breast cancer risk differently in African American women compared to other ethnic groups, and also differently for HR− breast cancer than HR+ breast cancer. What's new? Evidence suggests that breast cancer risk is influenced by endogenous estrogen exposure, a surrogate measure of which may be cumulative menstrual months (CMM). Here, associations between breast cancer risk and CMM were investigated for four major ethnic groups in the United States. Analyses reveal positive links between CMM and breast cancer risk in premenopausal and postmenopausal Asian Americans, Hispanics, and non‐Hispanic whites. An inverse association was detected among obese premenopausal African American women. The observed differences in risk in relation to CMM highlight the importance of ongoing investigations of breast cancer risk for diverse ethnic groups and breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose–response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case–control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk (risk ratio [RR] 1.11, 95% confidence interval-CI 1.07–1.15), with comparable associations in case–control studies (RR 1.14, 95% CI 0.98–1.34) and cohort studies (RR 1.10, 95% CI 1.06–1.15). In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women (premenopausal: RR 1.16, 95% CI 1.04–1.28; postmenopausal: 1.07, 95% CI 1.02–1.13) and for women with estrogen receptor (ER) positive breast cancer (ER + : RR 1.09, 95% CI 1.02–1.17; ER–: RR 1.07, 95% CI 0.92–1.23). The dose–response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cm2/sr after which the curve flattened, especially among premenopausal women. This first assessment of the dose–response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women. [ABSTRACT FROM AUTHOR]

Interleukin-17A (IL-17A) is a member of the Interleukin-17 family, which belongs to the pro-inflammatory cystine-knot cytokines. Recent studies on the etiology of breast cancer have focused on the role of immunity and inflammation. The pro-inflammatory cytokines IL-17A can medicate cancer-related inflammation. The present study aimed to analyze the mutation in physicochemical properties and structure of the Interleukin-17Agenein developing breast cancer using bioinformatics methods. A total of 60 blood samples were obtained from Iraqi women aged 25 to 75 with breast cancer. Twenty blood samples were obtained from healthy women in the same age range as a control group. Deletion and missense mutations detected by BLAST in samples with breast cancer. The present study determined the physicochemical properties of IL-17A such as hydrophilic nature, alpha-helical and 3D structure. The results of this study indicated that IL-17Ais considered a marker for a patient with breast cancer. Also, mutations in the IL-17Agene affect the structure and physicochemical properties of the IL-17A protein complex. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequent form of cancer and, even today, although there has been an improvement in prognosis, it remains the leading cause of cancer death in women. The objective of this study was to evaluate the quality of life and investigate the psychological, sexological and affective aspects in women with breast cancer, comparing them with a control group and identifying possible differences. The protocol, consisting of self-report tools, was administered to 97 women divided into two groups: the clinical group (n = 44 women with breast cancer) and the control group (n = 53 postmenopausal women). The analyzes sought to investigate which domains determined the significance in the comparison between the two groups. Sexual (FSFI) and distress (FSDS) functioning, psychological (SCL-90-R) and emotional (PANAS) functioning were assessed. Women with iatrogenic menopausal breast cancer showed greater sexual difficulties than women in natural menopause. Similarly, symptoms such as anxiety and depression are present to a greater or lesser extent in women in natural menopause, while they acquire greater value in those in which menopause has been induced early. The data that emerge from the study have significant implications both for future research and for the clinic, underlining how the biopsychosocial perspective is fundamental to fully understand the personal and relational experience connected to the pathology. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations.Methods: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors.Results: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes.Conclusions: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies. [ABSTRACT FROM AUTHOR]

Context: Topical management is the main form of control of signs and symptoms regarding malignant wounds (MWs) arising from tumor progression on the skin. Nevertheless, few studies have explored this theme and evidence on the effectiveness of the methods used to control bleeding is unknown, leading to a lack of consensus to support clinical practice.Objectives: Identify and evaluate current evidence on topical MW hemostasis from breast cancer and suggest new topics for future research.Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. Seven indexed databases were consulted using the terms: "breast neoplasms"; "breast cancer"; "malignant fungating wounds"; "malignant wounds"; "bleeding."Results: From the 112 articles identified in total, six were included in this review: a descriptive cohort study (n = 32), two case series (n = 21) and three case reports (n = 3). Fifty-six patients were exposed to 11 types of topical treatments using calcium alginate, surgical hemostats, adrenaline, nonadherent dressings, silver nitrate, modified Mohs Paste, and 10% formalin. There were no reports of significant adverse effects.Conclusion: Although studies have promoted positive results of topical hemostasis, scientific evidence is still weak and arises from studies with poor methodological quality. Randomized controlled trials were not identified. The results highlight the crucial need for pilot studies to evaluate effect size, study procedures, and measurable results. [ABSTRACT FROM AUTHOR]

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case‐control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population‐based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray‐Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13‐0.36; Ptrend <.001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen‐conjugating and immune‐related functions were strongly associated with breast cancer (all Ps <.001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially‐mediated mechanisms of breast disease. What's new? The gut microbiome has been shown to affect a variety of physiological systems throughout the body. These authors conducted the largest known study investigating the association of gut bacteria with breast disease in Ghana, where breast cancer incidence is rising. They sequenced the 16S rRNA gene of fecal bacteria among 895 women (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population‐based controls). They found that patients with breast cancer and non‐malignant breast disease had a similar fecal microbial profile, which differed from that of controls. Microbial alpha diversity was inversely associated with odds of breast cancer and non‐malignant breast disease. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have essential roles in the etiology of breast cancer and are regarded as possible markers in this malignancy. In order to find new markers for breast cancer, the current study has measured expression level of four miRNAs, namely miR-125a, miR-106b, miR-96 and miR-92a-3p in the paired breast samples. Expression levels of miR-125a and miR-106b were higher in tumoral tissues compared with control tissues (Expression ratios (95% CI) = 4.01 (1.96–8.19) and 3.9 (1.95–7.81); P values = 0.0005 and 0.0003, respectively). miR-106b and miR-125a differentiated between malignant and non-malignant tissues with AUC values of 0.7 and 0.67, respectively. We detected association between expression of miR-106b and clinical stage (P = 0.03), in a way that its expression was the lowest in the advanced stages. Finally, significant relationships were found between miR-96 and miR-125a in both tumoral and non-tumoral specimens (ρ = 0.76 and 0.69, respectively). This nonparametric measure of rank correlation also showed relationship between miR-106b and miR-96 in both sets of samples (ρ = 0.63 and 0.61, respectively). Cumulatively, the assessed miRNAs, particularly miR-125a and miR-106b are putative targets for further expression and functional assays in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Light at night (LAN) inhibits nighttime secretion of melatonin and may cause circadian disruption, which may be a risk factor for cancer. Recent studies have linked high LAN exposure with elevated breast cancer risk. Given that breast cancer may share a common hormone‐dependent etiology with thyroid cancer and that circadian rhythms play a role in regulating thyroid function, the authors hypothesized that exposure to LAN is positively associated with thyroid cancer incidence. Methods: This study examined the association between LAN and thyroid cancer incidence in the National Institutes of Health–American Association of Retired Persons Diet and Health Study. LAN exposure was estimated from satellite data and was linked to residential addresses at the baseline. Incident thyroid cancer cases were ascertained via linkage to state cancer registries. Cox regression was used to determine the relationship between LAN and thyroid cancer risk, with adjustments made for sociodemographic, lifestyle, and other environmental factors. Results: Among 464,371 participants, a positive association was found between LAN and thyroid cancer risk. Specifically, in comparison with the lowest quintile of LAN, the highest quintile was associated with a 55% increase in risk (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.18‐2.02). The association was primarily driven by papillary thyroid cancer and was stronger in women (HR, 1.81; 95% CI, 1.26‐2.60) than men (HR, 1.29; 95% CI, 0.86‐1.94). In women, the association was stronger for localized cancer, whereas in men, the association was stronger for a more advanced stage. Results were consistent across different tumor sizes. Conclusions: LAN was positively associated with thyroid cancer risk. Future studies are needed to confirm this association and identify underlying biological mechanisms. This study reports that higher exposure to light at night is associated with a higher risk for thyroid cancer. The association is stronger for women than men, and this cannot be fully explained by a detection bias. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities. Cancers in different populations have been shown to be genetically distinct. Here, the authors sequence breast cancers from Mexican-Hispanic patients and find that these patients have a higher percentage of Akt1 mutations compared to Caucasian and Asian populations, suggesting these are clinically actionable. [ABSTRACT FROM AUTHOR]

Background Studies suggest that fatty acid status influences breast cancer etiology, yet the roles of individual fatty acids in breast cancer risk are unclear, specifically when central adiposity and menopausal status are considered. Objectives This study examined the associations of fatty acid status with breast cancer risk including location, menopausal status, and waist-to-hip ratio as key variables. Methods Prediagnostic plasma phospholipid fatty acids were measured in women with breast cancer (n  = 393) and age-matched controls (n  = 786) from a nested case-control prospective study within Alberta's Tomorrow Project (ATP) and British Columbia Generations Project (BCGP) cohorts. Binary logistic regression models were used to evaluate associations of fatty acids and breast cancer risk with subgroup analysis for menopausal status and waist-to-hip ratio. Results Women from BCGP had a higher n–3 (ɷ-3) fatty acid status compared with the ATP (6.4% ± 0.08% vs. 5.3% ± 0.06%; P  < 0.001), so subsequent analysis was blocked by cohort. Overall, fatty acids had inconsistent associations with risk. In the ATP among premenopausal women, total long-chain n–3 fatty acids (ORQ4vsQ1 = 1.78; 95% CI: 0.58, 5.43; P- trend = 0.007, P- interaction = 0.07) were positively associated with breast cancer risk, whereas in BCGP, DHA (ORQ4vsQ1 = 0.66; 95% CI: 0.28, 1.53; P- trend = 0.03, P- interaction = 0.05) and total long-chain n–3 fatty acids (ORQ4vsQ1 = 0.66; 95% CI: 0.28, 1.54; P- trend = 0.03) were associated with decreased cancer risk when the waist-to-hip ratio was <0.85. Conclusions Our findings suggest that regional variations in fatty acid status influence breast cancer risk, resulting in positive associations of total long-chain n–3 fatty acids in premenopausal ATP women and negative associations of these fatty acids in BCGP women with a waist-to-hip ratio below guidelines. This study highlights the complexity and difficulty in using fatty acid status to predict breast cancer risk in diverse populations without the consideration of other risk factors. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the leading causes of mortality worldwide being the most common cancer among women. Despite the significant progress obtained during the past years in the understanding of breast cancer pathophysiology, women continue to die from it. Novel tools and technologies are needed to develop better diagnostic and therapeutic approaches, and to better understand the molecular and cellular players involved in the progression of this disease. Typical methods employed by the pharmaceutical industry and laboratories to investigate breast cancer etiology and evaluate the efficiency of new therapeutic compounds are still based on traditional tissue culture flasks and animal models, which have certain limitations. Recently, tumor-on-chip technology emerged as a new generation of in vitro disease model to investigate the physiopathology of tumors and predict the efficiency of drugs in a native-like microenvironment. These microfluidic systems reproduce the functional units and composition of human organs and tissues, and importantly, the rheological properties of the native scenario, enabling precise control over fluid flow or local gradients. Herein, we review the most recent works related to breast tumor-on-chip for disease modeling and drug screening applications. Finally, we critically discuss the future applications of this emerging technology in breast cancer therapeutics and drug development. Unlabelled Image • Breast cancer is one of the leading causes of mortality among women. • Microfluidics can address the challenges related to breast cancer progression. • Breast cancer physiopathology can be replicated using tumor-on-chip technology. • Tumor biomarkers can be precisely identified and analyzed. • Drug screening and discovery can be accelerated with microfluidics. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer deaths in women globally. In 2018, 2.1 million new cases were reported, with 627,000 deaths. Pakistan has the highest incidence rate of breast cancer among Asian countries: one in every nine women has a lifetime risk of being diagnosed with breast cancer. By reason of many misconceptions about the etiology of the disease and socioeconomic factors, Pakistani women have very low rates of early detection and diagnose breast cancer at advance stages with fewer chances of survival. The key to cure the breast cancer is early diagnosis. The aim of current review is to highlight the factors leading to the delays in early presentation of breast cancer in Pakistani women and to summarize possible recommendations for educating women about early diagnosis along with palliative care facilities for patients suffering from breast cancer. Furthermore, this study appeals to both the general public and government in the belief that better reporting and awareness campaigns may bring more women to clinics for early diagnosis. [ABSTRACT FROM AUTHOR]