Influence Breast Cancer Research Articles

Survival Analysis of Covariates Influencing Breast Cancer Treatment: A Case Study of North Eastern Nigeria

Summary This study builds on previous research indicating that breast cancer survival time is influenced by several underlying factors. The study covered a period of 10 years from January 2012 to December 2022, and 140 cases were considered within the study cohort. The study considered breast cancer patients from North East Nigeria. The methodologies used are Cox hazard proportional regression and Kaplan–Meier analysis. The mean patient survival time is 592.2 days, with an average age of 44.61 years, average number of children of 5, and mean weight difference of 1.95 kg while on treatment. Kaplan-Meier analysis and the log rank test were used to investigate how the various covariates affect survival time, and it was found that age and family history have significant effects on the survival time in the studied population. The p-value of 0.04 for radiotherapy indicates statistical significance, in contrast to other treatment options such as surgery (p-value 0.7), targeted therapy (p-value 0.7), and chemotherapy (p-value 0.6). Residual diagnostic analysis with a component for assessment of Variance Inflation Factors (VIF) was used to detect multicollinearity among the independent variables. A total of 60 events (deaths) occurred within the study period with a concordance value of 0.73, which indicates a moderate level of agreement. This implies that the model’s predictions align reasonably well with the observed outcomes.

Assessment of the HER2 Equivocal Cases in Breast Cancer Following Laterality

Background: Breast cancer is a leading cancer among Indian women. Approximately 15-30% of cases are linked to HER2 gene overexpression, impacting survival. Despite of the advancements in HER2-targeted therapies equivocal HER2 status poses diagnostic challenges and is comparatively less studied. Breast cancer also displays a peculiar laterality, with a consistent left-sided predominance, yet the underlying factors remain unclear. Methods: A retrospective analysis of 488 breast cancer cases with equivocal HER2 status confirmed by Fluorescent In-Situ Hybridization (FISH) was conducted. Data included age, hormone receptor status, molecular subtypes, grade, Ki67 status, and FISH scores. Statistical analysis was performed using the R language, and laterality ratios were calculated. Results: Left-sided breast cancer prevalence was 64.95%, with a laterality ratio of 1.85. Age-related variations and significant laterality preferences were observed in Grade III tumors. Molecular subtypes, particularly Triple Negative, exhibited distinct laterality patterns. Equivocal cases displayed varied FISH scores, emphasizing molecular heterogeneity. Conclusions: This study comprehensively analysis of HER2-equivocal breast cancer cases, shedding light on laterality patterns and their associations. The observed left-sided predominance suggests potential underlying factors, including age, tumor grade, and molecular subtypes. Understanding these sophistications is crucial for personalized treatment strategies and warrants further investigation into the complex interplay of clinicopathological factors influencing breast cancer laterality.

Effectiveness of the socioecological informed contextual treatment summary and care plan (TSSCP-P, Brazil) for breast cancer survivors: a randomized, controlled study

ObjectiveThis study aimed to evaluate the impact of an intervention using the Treatment Summary and Survivorship Care Plan (TSSCP-P) on self-efficacy and quality of life (QoL) in breast cancer survivors.MethodA clinical study, randomized and controlled, conducted to assess self-efficacy and QOL in breast cancer survivors. The participants were randomly assigned to either an intervention group or a control group. The intervention group received individualized nursing consultations guided by the TSSCP-P, while the control group received standard care. Self-efficacy and QoL were assessed at three evaluation moments using validated scales: Functional Assessment of Cancer Therapy-Breast Plus Anm Morbidity (FACT B + 4) and Perceived General Self-Efficacy Scale. Statistical analyses, including regression analysis and hypothesis tests, were conducted to examine the effects of the intervention on self-efficacy and QoL.ResultsFemale breast cancer survivors (N = 101) were recruited. The intervention group demonstrated a significant improvement in self-efficacy over time compared to the control group (p = 0.01). However, no significant differences were observed in the overall QoL scores between the two groups. Subscale analysis revealed a significant improvement in physical well-being for the intervention group (p = 0.04), while emotional well-being showed a non-significant improvement (p = 0.07). The study suggests that individualized care plans and support strategies, such as the TSSCP-P, can positively influence breast cancer survivors’ self-efficacy and certain aspects of their QoL.ConclusionThese findings highlight the potential benefits of the TSSCP-P intervention in enhancing self-efficacy among breast cancer survivors. However, further research is needed to explore its impact on overall QoL and its effectiveness across different stages of breast cancer, as well as with longer follow-up periods.Clinical trial registration numberBrazilian Registry of Clinical Trials (ReBEC- RBR-2m7qkjy; UTN code: U1111-1257–3560), registered in April 19th, 2022.

The Tumor Immune Microenvironment in Breast Cancer Progression.

The tumor microenvironment significantly influences breast cancer development, progression, and metastasis. Various immune cell populations, including T cells, B cells, NK cells, and myeloid cells exhibit diverse functions in different breast cancer subtypes, contributing to both anti-tumor and pro-tumor activities. This review provides an overview of the predominant immune cell populations in breast cancer subtypes, elucidating their suppressive and prognostic effects. We aim to outline the role of the immune microenvironment from normal breast tissue to invasive cancer and distant metastasis. A comprehensive literature review was conducted to analyze the involvement of immune cells throughout breast cancer progression. In breast cancer, tumors exhibit increased immune cell infiltration compared to normal tissue. Variations exist across subtypes, with higher levels observed in triple-negative and HER2+ tumors are linked to better survival. In contrast, ER+ tumors display lower immune infiltration, associated with poorer outcomes. Furthermore, metastatic sites commonly exhibit a more immunosuppressive microenvironment. Understanding the complex interaction between tumor and immune cells during breast cancer progression is essential for future research and the development of immune-based strategies. This comprehensive understanding may pave the way for more effective treatment approaches and improved patients outcomes.

Exploring human mammaglobin: as a possible diagnostic and prognostic indicator in breast cancer tissue

Breast cancer is a major global health issue, with high diagnosis rates worldwide, especially in less developed areas, leading to significant mortality rates. This review focuses on the molecular characteristics of breast cancer, emphasizing the role of human mammaglobin-A (hMAM-A) as a diagnostic and prognostic marker. hMAM-A, a dimeric protein from the secretoglobin family, is produced exclusively by breast tissue and shows elevated levels in breast cancer cases, making it a highly accurate marker for disease detection. The review also examines various factors influencing breast cancer, such as age, tobacco use, menopausal status, and hormone replacement therapy (HRT). Younger age at diagnosis is associated with poorer outcomes, highlighting the importance of early detection. Tobacco smoke increases mortality rates in breast cancer patients. Menopausal status affects molecular subtypes and risk factors, impacting treatment and prognosis. HRT has a complex relationship with breast cancer risk. The review concludes by discussing the need for novel biomarkers, including hMAM-A, to improve breast cancer diagnosis and management.

The involvement and application potential of exosomes in breast cancer immunotherapy.

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Socio-cultural beliefs and perceptions influencing diagnosis and treatment of breast cancer among women in Ghana: a systematic review

BackgroundBreast cancer is currently the most commonly diagnosed cancer in Ghana and the leading cause of cancer mortality among women. Few published empirical evidence exist on cultural beliefs and perceptions about breast cancer diagnosis and treatment in Ghana. This systematic review sought to map evidence on the socio-cultural beliefs and perceptions influencing the diagnosis and treatment of breast cancer among Ghanaian women.MethodsThis review was conducted following the methodological guideline of Joanna Briggs Institute and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The literature search was conducted in PubMed, CINAHL via EBSCOhost, PsycINFO, Web of Science, and Embase. Studies that were conducted on cultural, religious, and spiritual beliefs were included. The included studies were screened by title, abstract, and full text by three reviewers. Data were charted and results were presented in a narrative synthesis form.ResultsAfter the title, abstract, and full-text screening, 15 studies were included. Three categories were identified after the synthesis of the charted data. The categories included: cultural, religious and spiritual beliefs and misconceptions about breast cancer. The cultural beliefs included ancestral punishment and curses from the gods for wrongdoing leading to breast cancer. Spiritual beliefs about breast cancer were attributed to spiritual or supernatural forces. People had the religious belief that breast cancer is a test from God and they resorted to prayers for healing. Some women perceived that breast cancer is caused by spider bites, heredity, extreme stress, trauma, infections, diet, or lifestyle.ConclusionThis study adduces evidence of the socio-cultural beliefs that impact on the diagnosis and treatment of breast cancer among women in Ghana. Taking into consideration the diverse cultural and traditional beliefs about breast cancer diagnosis and treatment, there is a compelling need to intensify nationwide public education on breast cancer to clarify the myths and misconceptions about the disease. We recommend the need to incorporate socio-cultural factors influencing breast cancer diagnosis and treatment into breast cancer awareness programs, education, and interventions in Ghana.

Abstract PO4-08-01: Methylsterol monooxygenase 1 (MSMO1) modulates endoplasmic reticulum stress through cholesterol metabolic reprogramming to alter chemotherapy sensitivity in breast cancer

Abstract Background Endoplasmic reticulum stress (ER stress) is a process in which cells activate unfolded protein response and other signaling pathways in response to misfolded and unfolded protein aggregation and calcium ion balance disturbance in the endoplasmic reticulum cavity. Depending on the intensity of endoplasmic reticulum stress, it can not only induce chaperone expression to play a protective effect, but also induce apoptosis independently. Metabolic reprogramming is one of the characteristics of tumor, which refers to the metabolic changes that cells make in response to various stimuli. Here, we demonstrate that methylsterol monooxygenase 1 (MSMO1) regulates cellular cholesterol metabolism and influences breast cancer susceptibility to chemotherapy by regulating the relative intracellular T-MAS content. Methods RNA-seq was performed on core needle biopsy samples from 26 patients receiving neoadjuvant chemotherapy for breast cancer to screen for genes that may influence neoadjuvant chemotherapy sensitivity. Cell proliferation, CCK8 assay and apoptosis assay were performed for MSMO1 phenotype study. Transmission electron microscopy (TEM) was conducted to visualize the structure of endoplasmic reticulum. Western Blot was used to detect the activation level of the unfolded protein response pathway. The relative content of sterols in MSMO1 knockdown cells was detected by targeted lipid mass spectrometry. AO/PI staining of breast cancer organoids was performed to verify the effect of MSMO1 metabolic substrate T-MAS on chemotherapy drug sensitivity. Results RNA-seq of core needle biopsy samples from breast cancer patients receiving neoadjuvant chemotherapy suggested that MSMO1 was highly expressed in non-pCR patients, and clinical survival data suggested that MSMO1 was associated with poor prognosis in patients with all types of breast cancer, suggesting that MSMO1 might be related to chemotherapy sensitivity of breast cancer. Phenotypic experiments revealed that MSMO1 regulates chemotherapy sensitivity of breast cancer both in vivo and in vitro. Ectopic overexpression of MSMO1 promoted cancer cell resistance to chemotherapy. To uncover the underlying mechanisms, RNA-seq of MSMO1 knock-down cells were carried out and identified that MSMO1 was associated with ER stress. TEM and western blot assay indicated that downregulation of MSMO1 expression leads to endoplasmic reticulum swelling and activation of the unfolded protein response. Considering that MSMO1 is a cholesterol metabolizing enzyme, targeted lipids mass spectrometry was performed to detect the changes in the contents of various intermediate metabolites in the cholesterol pathway, which indicated that the relative content of T-MAS, a metabolic substrate of MSMO1, was significantly up-regulated in MSMO1 knockdown cells. Then, in order to verify whether this metabolite can independently regulate ER stress, breast cancer cells were given T-MAS externally, and TEM and Western Blot analysis indicated that T-MAS could induce ER stress and activate the unfolded protein response independently. Apoptosis assay and AO/PI staining of breast cancer organoids revealed that T-MAS can improve the sensitivity of breast cancer to chemotherapy drugs. Conclusion In summary, these results shed light on the role of MSMO1 in cholesterol metabolism reprogramming, which adjust the endoplasmic reticulum stress state of cells by changing the relative content of intracellular T-MAS, and thereby influencing the sensitivity of breast cancer chemotherapy. As an intermediate metabolite of cholesterol metabolism, T-MAS has potential clinical application value of chemotherapy sensitization. Citation Format: Hengyu Ren, Liren Wangxu, Yayun Chi, Jiong Wu. Methylsterol monooxygenase 1 (MSMO1) modulates endoplasmic reticulum stress through cholesterol metabolic reprogramming to alter chemotherapy sensitivity in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-01.

Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)

Abstract Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experimental arm is based on previous study findings. Timelines: -First patient in: January 2021 -Last patient in: December 2024 -Primary outcome analysis: Q1/2027 Current accrual: In June 2023, 255 patients were recruited; the majority of them in Germany. Contact: Prof. Dr. Toralf Reimer (eubreast-01@kliniksued-rostock.de), study chair Dr. Oreste D. Gentilini (gentilini.oreste@hsr.it), study co-chair Funding by Else Kroener-Fresenius Foundation, German Society of Senology, University of Rostock (Germany), and San Raffaele Hospital (Milan, Italy). Citation Format: Toralf Reimer, Bernd Gerber, Thorsten Kuehn, Nikola Bangemann, Anke Kleine-Tebbe, Andrea Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, Florentia Peintinger, Keyur Mehta, Sibylle Loibl, Edoardo Botteri, Oreste Gentilini. Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-10.

Abstract PO3-25-01: CTLA4 expression profiles and their association with clinical outcomes of breast cancer

Abstract The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. First, the expression of CTLA4 in pan-cancer was evaluated using the platforms of Oncomine. Afterward, the web-based bioinformatics platforms of GEPIA and UCLAN were used to compare the expression of CTLA4 in breast cancer and normal tissues. Next, we assessed the relationship between CTLA4 mRNA expression and prognosis in breast cancer patients using the PrognoScan Database, Kaplan-Meier Plotter, and R2: Kaplan-Meier Scanner. Additionally, the correlation between CTLA4 expression and immune cell infiltration in breast cancer and functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to elucidate the potential biological functions of CTLA4. Finally, we used the STRINGdb and cytoHubba plugin Cytoscape to create a PPI network and identify known and predicted structural essentials for CTLA4 functions and the top five hub genes. CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (p< 0.01). The CTLA4 mRNA levels in BRCA based on breast cancer subtypes of luminal, Human epidermal growth factor receptor 2 (HER-2), and Triple-negative breast cancer (TNBC) were considerably higher than in normal tissues (p< 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P< 0.001), and was correlated with clinicopathological characteristics including age, T-stage, estrogen receptors (ER), progesterone receptors (PR), and PAM50 (P< 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P< 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. This study provides suggestive evidence of the prognostic role of CTLA4 in breast cancer, which may be a therapeutic target for breast cancer. Furthermore, CTLA4 may influence breast cancer prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in breast cancer and set the stage for more research. Citation Format: Woo Chul Noh, Young Bum Yoo, Kyoung Sik Park, Sang Eun Nam, Seung Hwan Lim. CTLA4 expression profiles and their association with clinical outcomes of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-25-01.

Abstract PO4-09-09: Deep Immunoprofiling Demonstrates Racial Differences in the Peripheral Immune System in Women at Risk for Breast Cancer

Abstract Background: Disparities in breast cancer outcomes between Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) women have been attributed to NHB women presenting with more aggressive subtypes and later stage disease, differences in treatment receipt and adherence, access to care and tumor biology. However, previous work has shown that these known factors do not fully account for the observed disparities in outcomes. Systemic immune fitness is a factor not previously studied that may play a role in dictating disease progression and therapeutic responses. Numerous factors, including age and race, impact immune system function and understanding these changes is critical to address disparities in breast cancer outcomes. Here, we developed a pipeline for deep immunoprofiling of peripheral blood mononuclear cells (PBMC) at single cell resolution by full-spectrum flow cytometry. Using this pipeline, we sought to investigate whether there are differences in immune fitness between NHB and NHW women at high risk for developing breast cancer. Methods: PBMC were collected and processed from age-matched NHB and NHW women (n=20/cohort) identified as being at high risk for developing breast cancer through our institution’s B-PREP (Breast Cancer Personalized Risk Assessment Education and Prevention) clinic. Two custom antibody panels and protocols for comprehensive immunoprofiling of T and B cell subsets (T/B Panel), as well as monocytic, NK, and dendritic cell subsets (M/N/D Panel), along with functional and exhaustion markers were designed, optimized, and implemented. Traditional gating strategies were used to quantify proportions of canonical cell populations, and unbiased high dimensionality reduction analysis was performed using the OMIQ analysis platform to assess phenotypes and functional status of various immune cell subsets. Results: Significant differences between cohorts in abundance as well as phenotype of various cell populations were observed. Specifically, CD4+ follicular helper T cells, TEMRA CD8, and CD45RA Terminal Effector CD8+ cells were enriched in NHB women while PD-1+/CD3+ cells and PD-1+/CD8+ cells were enriched in the NHW women (Table). Additionally, several immunosuppressive and systemic inflammatory immune cell types were enriched in NHB women (Table). Conclusions: Deep immunoprofiling using single-cell spectral flow cytometry revealed differences in peripheral immune cells between NHB and NHW women at high risk for breast cancer. The significant enrichment of immunosuppressive monocytes and several activated NK cell populations in PBMC samples from NHB women relative to those from NHW women indicate an altered immune environment that may influence breast cancer development. Additional analysis, including a larger sample size and patients with invasive cancer, are ongoing to further understand if differences in immune fitness between NHB and NHW women are associated with disparities in breast cancer outcomes. Table: PBMC populations (% of CD45+) that are significantly enriched in NHB relative to NHW patients Citation Format: Esther Ogayo, Milos Spasic, Tasnim Rahman, Olga Kantor, Tari King, Peter van Galen, Sandra McAllister, Elizabeth Mittendorf. Deep Immunoprofiling Demonstrates Racial Differences in the Peripheral Immune System in Women at Risk for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-09.

Improving Breast Cancer Outcomes for Indigenous Women in Australia.

In Australia, the incidence rate of breast cancer is lower in Indigenous* women than non-Indigenous women; however, the mortality rate is higher, with Indigenous women 1.2 times more likely to die from the disease. This paper provides practical and achievable solutions to improve health outcomes for Indigenous women with breast cancer in Australia. This research employed the Context-Mechanism-Outcome (CMO) framework to reveal potential mechanisms and contextual factors that influence breast cancer outcomes for Indigenous women, stratified into multiple levels, namely, micro (interpersonal), meso (systemic) and macro (policy) levels. The CMO framework allowed us to interpret evidence regarding Indigenous women and breast cancer and provides nine practical ways to improve health outcomes and survival rates.

Factors influencing breast cancer screening practices among women worldwide: a systematic review of observational and qualitative studies

BackgroundThe variation in breast cancer incidence rates across different regions may reflect disparities in breast cancer screening (BCS) practices. Understanding the factors associated with these screening behaviors is crucial for identifying modifiable elements amenable to intervention. This systematic review aims to identify common factors influencing BCS behaviors among women globally.MethodsRelevant papers were sourced from PubMed, Scopus, Embase, and Google Scholar. The included studies were published in English in peer-reviewed journals from January 2000 to March 2023 and investigated factors associated with BCS behaviors.ResultsFrom an initial pool of 625 articles, 34 studies (comprising 29 observational and 5 qualitative studies) with 36,043 participants were included. Factors influencing BCS behaviors were categorized into nine groups: socio-demographic factors, health status history, knowledge, perceptions, cultural factors, cues to action, motivation, self-efficacy, and social support. The quality appraisal scores of the studies ranged from average to high.ConclusionsThis systematic review highlights factors pivotal for policy-making at various levels of breast cancer prevention and assists health promotion professionals in designing more effective interventions to enhance BCS practices among women.

Adherence to Diet Quality Indices and Breast Cancer Risk in the Italian ORDET Cohort.

Breast cancer (BC) is the most common cancer in women, with 2.3 million diagnoses in 2020. There is growing evidence that lifestyle factors, including dietary factors, particularly the complex interactions and synergies between different foods and nutrients (and not a single nutrient or food), may be associated with a higher risk of BC. The aim of this work was to evaluate how the Italian Mediterranean Index (IMI), the Greek Mediterranean Index, the DASH score, and the EAT-Lancet score can help lower the risk of BC, and analyze if chronic low-grade inflammation may be one of the possible mechanisms through which dietary patterns influence breast cancer risk. We evaluated the effect of adherence to these four dietary quality indices in the 9144 women of the ORDET cohort who completed a dietary questionnaire. The effect of adherence to dietary patterns on chronic inflammation biomarkers was evaluated on a subsample of 552 participants. Hazard ratios (HRs) with 95% confidence intervals (CIs) for BC risk in relation to the index score categories used were estimated using multivariable Cox models adjusted for potential confounders. Regression coefficients (β), with 95% CI for C-reactive protein (CRP), TNF-α, IL-6, leptin, and adiponectin levels in relation to adherence to dietary patterns were evaluated with the linear regression model adjusted for potential confounders. IMI was inversely associated with BC in all women (HR: 0.76, 95% CI: 0.60-0.97, P trend = 0.04), particularly among postmenopausal women (HR: 0.64, 95% CI: 0.42-0.98, P trend = 0.11). None of the other dietary patterns was associated with BC risk. Higher IMI and Greek Mediterranean Index scores were inversely associated with circulating CRP (β: -0.10, 95% CI: -0.18, -0.02, and β: -0.13, 95% CI: -0.21, -0.04). The higher score of the EAT-Lancet Index was instead associated with a higher concentration of circulating levels of CRP (β: 0.10, 95% CI: 0.02, 0.18). In conclusion, these results suggest that adherence to a typical Italian Mediterranean diet protects against BC development, especially among postmenopausal women, possibly through modulation of chronic low-grade inflammation.

Factors Affecting Breast Cancer Screening Behavior Among Women in Saudi Arabia: A Retrospective Cross-Sectional Study.

Background Early detection of breast cancer is crucial for effective treatment and minimizing mortality, requiring effective screening methods like self-examination, clinical examination, and mammography. However, not all women in Saudi Arabia comply with these examinations, and studies examining its practice and barriers of low uptake are scant. The aim of this study is to investigate factors influencing breast cancer screening behavior among women in Saudi Arabia. Methods This cross-sectional study involving 806 women from October to November 2022 used an online questionnaire for the data collection process, including questions about demographic characteristics, awareness assessment, breast cancer screening behavior, symptoms, risk factors, and screening programs. Factors affecting the screening behavior were analyzed using the logistic regression model with adjusted odds ratio (AOR) and 95% confidence interval (CI). Results Among the 806 women who participated in the study, 479 (59.4%) were under 40 years old, and half of them were urban residents (n = 394, 48.9%). Only 134 subjects (16.6%) had a history of breast screening. Social media (n = 519, 64.5%) was the predominant source of screening information. The primary obstacles to breast cancer screening were the absence of tumor symptoms (n = 333, 41.3%), insufficient knowledge about early detection (n = 249, 31%), lack of time (n = 245, 30%), fear of discovering a tumor (n = 187, 23%), and lack of awareness about screening centers (n = 155, 19%).In regression analysis, predictive factors for breast cancer screening behavior were as follows: age over 40 years old (AOR: 2.56; 95% CI: 1.70-3.87), residents of big cities (AOR: 3.57; 95% CI: 1.02-12.56), positive family history of breast cancer (AOR: 2.53; 95% CI: 1.50-4.28), proximity to the screening center (AOR: 2.56; 95% CI: 1.22-5.39), and using contraceptive pills for more than five years (AOR: 1.78; 95% CI: 1.04-3.04), and were statistically significant (all p-values < 0.05). Conclusions In this study, the most perceived barriers to BSE were the absence of tumor symptoms, followed by insufficient knowledge about early detection, lack of time, fear of discovering a tumor, and lack of awareness about screening centers. Additionally, the predictive factors for breast cancer screening behavior were as follows: age over 40 years old, residents of big cities, positive family history of breast cancer, proximity to the screening center, and using contraceptive pills for more than five years. Given the identified factors affecting breast self-examination behavior in this study, public education initiatives are crucial for raising awareness, facilitating self-examination, and ultimately improving health outcomes and reducing breast cancer treatment costs in society.

Exosomal miR-182-5p from breast cancer cells reprogram tumor-associated macrophages and promotes TNBC progression by targeting Notch1 in macrophages

IntroductionThe regulatory role of miR-182 in breast cancer malignancy and macrophage reprogramming is well-established. However, the mechanisms through which miR-182 overexpression in tumor cells influences macrophage polarization remain elusive.Material and methodsAfter transfection with miR-182-5p mimics, inhibitors, and controls for 24 hours, exosomes were extracted by differential centrifugation from transfected MDA-MB-231. Macrophages co-cultured with these exosomes to illustrate the regulative effects of exo-miR-182-5p reprogram macrophage. Furthermore, breast cancer cells co-cultured with exo-miR-182-5p reprogrammed M2 macrophages to demonstrate the effects of reprogrammed M2 macrophages to influence breast cancer progression. After all, these findings were validated in cell derived xenograft (CDX) BALB/C nude-mice model.ResultsIn this study, we demonstrate that exosome-derived miR-182-5p from TNBC cells reprograms M2 macrophage polarization through direct combined with Notch1, thereby enhancing breast cancer progression in vitro and in vivo. When co-cultured with exosomes from TNBC cells transfected with miR-182-5p mimics or inhibitors, macrophages showed altered Notch1/Hes1 pathway expression, leading to M2 polarization and subsequent changes in reactive oxygen species (ROS), inflammation, and other biochemical markers. Furthermore, breast cancer cells co-cultured with exosomes reprogrammed macrophages exhibited increased colony formation, migration, and invasion, as well as reduced apoptosis. These findings were validated in a BALB/C nude-mice model.ConclusionsThis study pioneers the elucidation of the feedback loop mechanism between breast cancer cells and macrophages mediated by the exosome-derived miR-182-5p/Notch1 pathway, highlighting its role in macrophage reprogramming. Although the therapeutic application of miR-182-5p inhibitors as anticancer agents remains in the early stages, targeting macrophage polarization represents a promising avenue for breast cancer therapy.

ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

Breast Cancer in Patients with Previous Endometriosis Showed Low Aggressive Subtype.

Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.

Concomitant medication, comorbidity and survival in patients with breast cancer

Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform (https://adrenaline.curie.fr). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.

Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast Cancer.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, that subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer biology and potential therapeutic strategies.