Breast Cancer Prevention Research Articles

Analysis of Lethal Factors in Patients with Breast Cancer

Breast cancer is a common malignant tumor in women. The relatively early age for the occurrence of breast cancer is generally 20 years old. The largest number of people are between 45 and 50 years old. Breast cancer is the most significant female killer. China's breast cancer cases occupy 30% of the world's total amount, showing an increasing trend nowadays. To inhibit the increase in the mortality rate of breast cancer, it is particularly urgent to explore the lethal factors of breast cancer. In this paper, the author uses the collinearity test to eliminate the closely related variables in the independent variables. Then, the author uses the binary logic regression method to obtain the relationship coefficient between each factor and breast cancer death. Finally, the author finds that the main factors of breast cancer death are age, T stage, N stage, differentiate, Estrogen Status, and Survival Months. This article provides new ideas for breast cancer prevention and treatment, hopes that breast cancer patients can prolong their lifespan, and hopes to contribute to breast cancer research worldwide.

The Challenge of Deep Learning for the Prevention and Automatic Diagnosis of Breast Cancer: A Systematic Review.

This review aims to evaluate several convolutional neural network (CNN) models applied to breast cancer detection, to identify and categorize CNN variants in recent studies, and to analyze their specific strengths, limitations, and challenges. Using PRISMA methodology, this review examines studies that focus on deep learning techniques, specifically CNN, for breast cancer detection. Inclusion criteria encompassed studies from the past five years, with duplicates and those unrelated to breast cancer excluded. A total of 62 articles from the IEEE, SCOPUS, and PubMed databases were analyzed, exploring CNN architectures and their applicability in detecting this pathology. The review found that CNN models with advanced architecture and greater depth exhibit high accuracy and sensitivity in image processing and feature extraction for breast cancer detection. CNN variants that integrate transfer learning proved particularly effective, allowing the use of pre-trained models with less training data required. However, challenges include the need for large, labeled datasets and significant computational resources. CNNs represent a promising tool in breast cancer detection, although future research should aim to create models that are more resource-efficient and maintain accuracy while reducing data requirements, thus improving clinical applicability.

Biomimetic Anisotropic-Functionalized Platelet-Membrane-Coated Polymeric Particles for Targeted Drug Delivery to Human Breast Cancer Cells.

Biomimetic particles that can replicate aspects of natural biological cell function are useful for advanced biological engineering applications. Engineering such particles requires mimicking the chemical complexity of the surface of biological cells, and this can be achieved by coating synthetic particles with naturally derived cell membranes. Past research has demonstrated the feasibility of utilizing cell membrane coatings from a variety of cell types to achieve extended blood circulation half-life. A particle's shape can also be designed to mimic a biological cell or virus, and this physical attribute can cause particular transport and biodistribution properties. However, the potential synergy between engineering a biomimetic particle's core shape in combination with functionalizing its surface with cell membranes to achieve targeted drug delivery has not been well-investigated. Here, anisotropic poly(lactic-co-glycolic acid) (PLGA) particles are coated with platelet membranes to engineer particles with enhanced stealth properties that are biomimetic in size, shape, and surface composition to natural platelets. The natural ability of platelets to target tumor cells was harnessed to develop a particulate system for targeted dual delivery of a small molecule and protein to cancer cells. The particles had targeted binding to metastatic human breast cancer cells, leading to enhanced killing of these cells in a mouse model through codelivery of TRAIL and doxorubicin. This system can be used for cancer cell killing and could potentially be utilized in preventing breast cancer metastasis. By engineering both the physical and chemical properties of the particles, biomimicry and therapeutic promise can be best achieved.

Modifiable Risk Factors for Breast Cancer: Insights From Systematic Reviews.

To conduct a comprehensive review of reversible factors associated with breast cancer, with the aim of offering insights for the creation of early intervention strategies for breast cancer prevention. The PubMed, EMBASE, and Scopus databases were systematically searched to collect systematic reviews and meta-analyses related to breast cancer risk. Searches were limited to literature published from the inception of each database up to May 1, 2024. Two investigators independently screened the literature, extracted data, and assessed the methodological quality and evidence synthesis of the studies included in our review. We included 31 systematic reviews in our analysis, and breast cancer risk factors were divided into four categories: diet and lifestyle habits, reproductive and familial factors, body weight and physical activity, and environmental and miscellaneous factors. Our findings suggest that a high-fat diet, low intake of dietary fiber, alcohol consumption, smoking, and obesity are linked to a higher risk of breast cancer. Conversely, physical activity and breastfeeding appear to lower breast cancer risk. However, the methodological and evidence quality of the reviewed studies was generally low, necessitating caution in the application of these findings. Additionally, there is a need for more research into lifestyle interventions to better develop and advocate for effective breast cancer prevention strategies.

Swedish Genome-Wide Haplotype Association Analysis Suggests Breast Cancer Loci with Varying Risk-Modifying Effects.

Background: To find support for risk-modifying genes in breast cancer, a haplotype GWAS in sporadic breast cancer cases was undertaken. The results were compared with the results from previous analyses in familial cases and all cases from the same Swedish cohort. Methods: In total, 2550 women with sporadic invasive breast cancer and 5021 healthy controls were included in a sliding-window haplotype GWAS using PLINK 1.07. Results: The analysis of sporadic cases confirmed the loci on chromosomes 10q26.13, 11q13.3, and 16q12.1 and suggested one novel locus on chromosome 12p11.21 (OR = 1.42 p = 4.55 × 10-8). A comparison between these loci and the same loci in the analyses of familial cases and all breast cancer cases was undertaken. Conclusions: Haplotype GWAS in sporadic cases of Swedish breast cancer cases supported known risk loci and suggested another risk locus. The loci identified in the analysis of sporadic and all breast cancer cases were suggested to act as modifiers of the risk of breast cancer. Haplotype analysis identified other loci with higher odds ratios than single-variant analysis. Further studies are needed to find out how to best include the findings in breast cancer prevention.

Expression Patterns of ER, PR, Her2/neu, and Ki67 in Sudanese Breast Cancer Patients

Background: Tumor markers are crucial indicators for breast cancer treatment and follow-up. Thus, this study attempted to explore the expression patterns of ER, PR, Her2/neu, and Ki67 in Sudanese breast cancer patients. Methodology: This study was a retrospective descriptive analysis conducted in El-Obeid city, Sudan. Records of 190 patients were obtained, including 110 with malignant lesions and 79 with benign breast lesions, from two histopathology laboratories. Results: Approximately 37% of patients were ER/PR positive, whereas 31% of cases tested for ER, PR, and Her2/neu were classified as triple negative. Ki-67 expression exhibited significant variability among breast lesions. Invasive ductal carcinoma (IDC) exhibited the highest expression of estrogen receptors (ER) at 59%, followed by progesterone receptors (PR) at 56%, and HER2 positivity at 53.8%. Conclusion: Breast cancer cases in Sudan are prevalent, characterized by ER/PR positivity, triple-negative status, and elevated Ki-67 expression. The predominant histological type of breast cancer is invasive ductal carcinoma. Women under the age of 45 exhibit a higher susceptibility to breast cancer. A significant number of patients exhibit advanced stages of the disease. Sudan advocates for the prevention and early detection of breast cancer.

Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.

Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.

Causality between gut microbiota, immune cells, and breast cancer: Mendelian randomization analysis.

The association between gut microbiota (GM) and breast cancer (BC) has been studied. Nevertheless, the causal relationship between them and the potential mediating factors have not been clearly defined. Therefore, in this study, Mendelian randomization analysis (MR) was employed to explore the causal relationship between 473 GM and BC, as well as the mediating effect of potential immune cells. In this investigation, we availed ourselves of the publicly accessible summary statistics from the genome-wide association study to undertake two-sample and reverse Mendelian randomization analyses on GM and BC, with the intention of clarifying the causal association between GM and BC. Subsequently, through the application of the two-step Mendelian randomization analysis, it was revealed that the relationship between GM and BC was mediated by immune cells. The stability of the research outcomes was verified via sensitivity analysis. Mendelian randomization analysis elucidated the protective impacts of 8 genera on BC (such as Phylum Actinobacteriota, Species Bacteroides A plebeius A, Species Bifidobacterium adolescentis, Species CAG-841 sp002479075, Family Fibrobacteraceae, Order Fibrobacterales, Class Fibrobacteria, and Species Phascolarctobacterium sp003150755). Additionally, there are 23 immune cell traits related to BC. Our research findings showed that the species Megamonas funiformis was associated with an increased risk of BC, and 11.20% of this effect was mediated by CD38 on IgD+ CD24-. Likewise, HLA DR on CD33br HLA DR+ CD14- mediated the causal relationship between Species Prevotellamassilia and BC, having a mediating ratio of 7.89%. This study clarifies a potential causal relationship between GM, immune cells, and BC and provides genetic evidence for this causal connection. It offers research directions for the subsequent prevention and treatment of BC through the interaction between GM and immune cells, and provides a reference for future mechanistic and clinical studies in this field.

DNA-methylation age and accelerated epigenetic aging in blood as a tumor marker for predicting breast cancer susceptibility.

DNA methylation (DNAm)-based marker of aging, referred to as 'epigenetic age' or 'DNAm age' is a highly accurate multi-tissue biomarker for aging, associated with age-related disease risk, including cancer. Breast cancer (BC), an age-associated disease, is associated with older DNAm age and epigenetic age acceleration (age accel) at tissue levels. But this raises a question on the predictability of DNAm age/age accel in BC development, emphasizing the importance of studying DNAm age in pre-diagnostic peripheral blood (PB) in BC etiology and prevention. We included postmenopausal women from the largest study cohort and prospectively investigated BC development with their pre-diagnostic DNAm in PB leukocytes (PBLs). We estimated Horvath's pan-tissue DNAm age and investigated whether DNAm age/age accel highly correlates with risk for developing subtype-specific BC and to what degree the risk is modified by hormones and lifestyle factors. DNAm age in PBLs was tightly correlated with age in this age range, and older DNAm age and epigenetic age accel were significantly associated with risk for developing overall BC and luminal subtypes. Of note, in women with bilateral oophorectomy before natural menopause experiencing shorter lifetime estrogen exposure than those with natural menopause, epigenetic age accel substantially influenced BC development, independent of obesity status and exogeneous estrogen use. Our findings contribute to better understanding of biologic aging processes that mediate BC carcinogenesis, detecting a non-invasive epigenetic aging marker that better reflects BC development, and ultimately identifying the elderly with high risk who can benefit from epigenetically targeted preventive interventions.

CircRNAs and miRNAs: Key Player Duo in Breast Cancer Dynamics and Biomarkers for Breast Cancer Early Detection and Prevention.

Breast cancer (BC) remains a significant global health issue, necessitating advanced molecular approaches for early detection and prevention. This review delves into the roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in BC, highlighting their potential as non-invasive biomarkers. Utilizing in silico tools and databases, we propose a novel methodology to establish mRNA/circRNA/miRNA axes possibly indicative of early detection and possible prevention. We propose that during early tumor initiation, some changes in oncogene or tumor suppressor gene expression (mRNA) are mirrored by alterations in corresponding circRNAs and reciprocal changes in sponged miRNAs affecting tumorigenesis pathways. We used two Gene Expression Omnibus (GEO) datasets and identified five mRNA/circRNA/miRNA axes as early possible tumor initiation biomarkers. We further validated the proposed axes through a Kaplan-Meier (KM) plot and enrichment analysis of miRNA expression using patient data. Evaluating coupled differential expression of circRNAs and miRNAs in body fluids or exosomes provides greater confidence than assessing either, with more axes providing even greater confidence. The proposed methodology not only improves early BC detection reliability but also has applications for other cancers, enhancing preventive measures.

The Untapped Opportunities of Addressing Lifecourse Growth in Mammographic Breast Density and Breast Cancer Prevention in Non-Hispanic Black Women.

This commentary discusses the importance of adiposity and lifecourse growth with mammographic breast density (MBD) in non-Hispanic Black (NHB) women. Although high MBD is a well-established risk factor for breast cancer, the determinants of MBD in NHB women remain understudied. Although adiposity at the time of mammography is most strongly associated with MBD, adiposity as early as ages 10 and 18 years is also independently associated with MBD. The commentary emphasizes the need for future research to identify biological mechanisms underlying the associations of adulthood adiposity and lifecourse growth with MBD in NHB women and how these can be translated to breast cancer prevention. Additionally, it highlights the need for more studies looking at lifecourse growth and microscopic breast tissue characteristics such as terminal duct lobular unit involution and epithelial-to-stromal proportions. See related article by Bigham et al., p. 1640.

Selecting the Right Dose to Move Breast Cancer Prevention Forward.

The uptake and adherence of preventive therapy of breast cancer in clinical practice are low because of fear of serious adverse events and menopausal symptoms. Low-dose tamoxifen has been shown to retain efficacy while reducing toxicity in high-risk women. In this issue of the journal, Cornell and colleagues evaluated uptake, adherence, and tolerability of low-dose tamoxifen in high-risk women. More than 70% of patients reported that they took low-dose tamoxifen after counseling and were still taking the medication at 1 year. This paradigm shift may move the field of breast cancer prevention forward and reduce breast cancer incidence and mortality. See related article by Cornell et al., p. 565.

Relationship Between Perceived COVID-19 Risk and Change in Perceived Breast Cancer Risk: Prospective Observational Study.

Whether COVID-19 is associated with a change in risk perception about other health conditions is unknown. Because COVID-19 occurred during a breast cancer study, we evaluated the effect of COVID-19 risk perception on women's breast cancer risk perception. This study aims to evaluate the relationship between perceived risk of COVID-19 and change in perceived breast cancer risk. We hypothesized that women who perceived greater COVID-19 risk would evidence increased perceived breast cancer risk and this risk would relate to increased anxiety and missed cancer screening. Women aged 40-74 years with no breast cancer history were enrolled in a US breast cancer prevention trial in outpatient settings. They had provided breast cancer risk perception and general anxiety before COVID-19. We performed a prospective observational study of the relationship between the perceived risk of COVID-19 and the change in perceived breast cancer risk compared to before the pandemic. Each woman was surveyed up to 4 times about COVID-19 and breast cancer risk perception, general anxiety, and missed medical care early in COVID-19 (May to December 2020). Among 13,002 women who completed a survey, compared to before COVID-19, anxiety was higher during COVID-19 (mean T score 53.5 vs 49.7 before COVID-19; difference 3.8, 95% CI 3.6-4.0; P<.001) and directly related to perceived COVID-19 risk. In survey wave 1, anxiety increased by 2.3 T score points for women with very low perceived COVID-19 risk and 5.2 points for those with moderately or very high perceived COVID-19 risk. Despite no overall difference in breast cancer risk perception (mean 32.5% vs 32.5% before COVID-19; difference 0.24, 95% CI -0.47 to 0.52; P=.93), there was a direct relationship between change in perceived breast cancer risk with COVID-19 risk perception, ranging in survey wave 4 from a 2.4% decrease in breast cancer risk perception for those with very low COVID-19 risk perception to a 3.4% increase for women with moderately to very high COVID-19 risk perception. This was not explained by the change in anxiety or missed cancer screening. After adjustment for age, race, education, and survey wave, compared to women with very low perceived COVID-19 risk, perceived breast cancer risk increased by 1.54% (95% CI 0.75%-2.33%; P<.001), 4.28% (95% CI 3.30%-5.25%; P<.001), and 3.67% (95% CI 1.94%-5.40%; P<.001) for women with moderately low, neither high nor low, and moderately or very high perceived COVID-19 risk, respectively. Low perceived COVID-19 risk was associated with reduced perceived breast cancer risk, and higher levels of perceived COVID-19 risk were associated with increased perceived breast cancer risk. This natural experiment suggests that a threat such as COVID-19 may have implications beyond the pandemic. Preventive health behaviors related to perceived risk may need attention as COVID-19 becomes endemic.

Improving communication to increase uptake of high-risk breast cancer prevention appointments: Building a better letter

ObjectiveMailed letters to women identified as being at high-risk for developing breast cancer were not having the desired effect for encouraging appointments with prevention-focused providers at a large Midwest healthcare system. A partnership with communication scholars sought to revise the letter to increase awareness, intentions, and appointments. MethodsGuided by the Extended Parallel Process Model, survey responses were collected from letter recipients over the course of two years, both pre and post letter revision. Appointments attributed to letters were also tracked. ResultsRecipients of the revised letter had increased knowledge regarding the length of prevention appointments and indicated greater self-efficacy and intentions to make and attend appointments compared to those who received the non-revised letter. A greater percentage who received the revised letter also made appointments. ConclusionPartnering with communication scholars helped with improving a letter mailed to thousands of patients each year. Finding ways to increase response-efficacy of breast cancer prevention activities within communications may assist in increasing appointments. InnovationCross-disciplinary partnerships across the medical and social sciences – while not quick or simple - are essential for finding ways to improve patient wellbeing and hopefully reducing the prevalence of preventable diseases in the future.

Knowledge, practice, and attitudes regarding breast cancer self-examination among women of reproductive age in Saudi Arabia: a community-based study.

Breast cancer is the second most common cancer among females worldwide and can often be detected at an early stage through breast self-examination (BSE). However, in many developing countries, most cases are diagnosed at advanced stages. This study aimed to assess the knowledge and practice of BSE among women of reproductive age in Saudi Arabia. This study adopted a community-based descriptive-analytical cross-sectional design. A stratified simple random sampling technique was used, with 50 participants from each region. Almost 500 Saudi women who fulfilled the inclusion criteria were enrolled in this study, and of these, 32.8% were within the age group of 20-29, 30.4% were within the age group of 30-39, and 32.8% were within the age group of more than 40 years. The overall knowledge score regarding BSE items among participants was 38%. Significant associations were found between breast cancer knowledge scores and demographic factors such as age group, educational level, marital status, region, and residence area (P < 0.05). Regarding knowledge of breast cancer risk factors, 48% of participants demonstrated poor knowledge, 43% had moderate knowledge, and only 9% had good knowledge. Effective prevention of breast cancer requires awareness and understanding of its risk factors. It is important for young women, starting from puberty, to be educated about potential changes in breast tissue and to receive proper training in BSE techniques from healthcare professionals.

Low Dose Tamoxifen for Breast Cancer Prevention: A Real-World Experience.

There is limited data on the use of low dose tamoxifen (LDT) for chemoprevention since its introduction in 2019. This study sought to determine the rate of LDT uptake at our institution and describe factors associated with its use. We performed a retrospective chart review of women diagnosed with ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), and/or atypical hyperplasia from 2019 to 2021. Log-binomial models were used to compare the probabilities of receiving standard dose tamoxifen (SDT) relative to LDT by patient and disease characteristics. Since most patients did not experience any AEs, a zero-inflated poison regression model was used to estimate and compare adverse event rates between groups. Among 477 patients with DCIS, LCIS, and atypical hyperplasia, 27% (N = 129) initiated SDT, 19% (N = 89) LDT, 32% (N = 155) aromatase inhibitor, 2% (N = 9) raloxifene, and 20% (N = 95) declined therapy. LDT was used more frequently than SDT in patients with LCIS or atypical hyperplasia compared to DCIS (31.4% vs 17.4%, P < .0001). There were no significant differences in the frequency of adverse events between patients on SDT and LDT but the incidence rate of AEs in the SDT group was higher (1.9 vs. 1.3 per 1000 days, P = .0186). In our population, 19% of women with DCIS, LCIS, or atypical hyperplasia, initiated chemoprevention with LDT with higher usage in patients with atypical lesions and/or LCIS. Physicians should strongly consider LDT in women with high-risk lesions who are eligible for chemoprevention.

Intervention-Related Changes in Coping Ability Drives Improvements in Mood and Quality of Life for Patients Taking Adjuvant Endocrine Therapy.

A recent randomized trial of a group psychosocial telehealth intervention (STRIDE) improved anxiety, depression, quality of life (QOL), symptom distress, coping, and self-efficacy to manage symptoms related to taking adjuvant endocrine therapy (AET) in women with non-metastatic hormone receptor-positive breast cancer. This study examined whether changes in coping and self-efficacy mediated intervention effects on anxiety, depression, QOL, and symptom distress. Women (N=100) were recruited between 10/2019-06/2021 from Massachusetts General Hospital and were randomized to STRIDE or to the medication monitoring control group. Participants completed self-report measures of anxiety and depression (Hospital Anxiety and Depression Scale), QOL (Functional Assessment of Cancer Therapy-Breast Cancer scale), symptom distress (Breast Cancer Prevention Trial Symptom Scale), coping (Measure of Current Status-Part A), and self-efficacy (Self Efficacy for Managing AET Symptoms) at baseline and 24-week follow-up. Mediated regression models tested whether changes in coping ability and self-efficacy mediated the intervention effects on anxiety, depression, QOL, and symptom distress, controlling for key variables. Improvements in coping across the 24-week study period mediated the effect of STRIDE on anxiety symptoms (indirect effect, B=-0.61, SE=0.28, 95% CI: -1.28, -0.17), depressive symptoms (indirect effect, B=-0.50, SE=0.21, 95% CI: -0.97, -0.15), and QOL (indirect effect, B=3.80, SE=1.25, 95% CI: 1.54, 6.49), but not symptom distress. Changes in self-efficacy did not mediate improvements in any of the proposed outcomes. Coping is an essential component of a brief group psychosocial intervention that drives improvements in mood and QOL for women with non-metastatic hormone receptor-positive breast cancer taking AET. NCT03837496.

De novo lipogenesis protects dormant breast cancer cells from ferroptosis and promotes metastasis.

Dormant disseminated tumor cells (DTCs) remain viable for years to decades before establishing a clinically overt metastatic lesion. DTCs are known to be highly resilient and able to overcome the multiple biological hurdles imposed along the metastatic cascade. However, the specific metabolic adaptations of dormant DTCs remain to be elucidated. Here, we reveal that dormant DTCs upregulate de novo lipogenesis and favor the activation and incorporation of monounsaturated fatty acids (MUFAs) to their cellular membranes through the activation of acyl-coenzyme A synthetase long-chain family member 3 (ACSL3). Pharmacologic inhibition of de novo lipogenesis or genetic knockdown of ACSL3 results in lipid peroxidation and non-apoptotic cell death through ferroptosis. Clinically, ACSL3 was found to be overexpressed in quiescent DTCs in the lymph nodes of breast cancer patients and to significantly correlate with shorter disease-free and overall survival. Our work provides new insights into the molecular mechanisms enabling the survival of dormant DTCs and supports the use of de novo lipogenesis inhibitors to prevent breast cancer metastasis.

Polyphenols as Immunomodulators and Epigenetic Modulators: An Analysis of Their Role in the Treatment and Prevention of Breast Cancer.

Breast cancer poses a substantial health challenge for women globally. Recently, there has been a notable increase in scholarly attention regarding polyphenols, primarily attributed to not only the adverse effects associated with conventional treatments but also their immune-preventive impacts. Polyphenols, nature-derived substances present in vegetation, including fruits and vegetables, have received considerable attention in various fields of science due to their probable wellness merits, particularly in the treatment and hindrance of cancer. This review focuses on the immunomodulatory effects of polyphenols in breast cancer, emphasizing their capacity to influence the reaction of adaptive and innate immune cells within the tumor-associated environment. Polyphenols are implicated in the modulation of inflammation, the enhancement of antioxidant defenses, the promotion of epigenetic modifications, and the support of immune functions. Additionally, these compounds have been shown to influence the activity of critical immune cells, including macrophages and T cells. By targeting pathways involved in immune evasion, polyphenols may augment the capacity of the defensive system to detect and eliminate tumors. The findings suggest that incorporating polyphenol-rich foods into the diet could offer a promising, collaborative (integrative) approach to classical breast cancer remedial procedures by regulating how the defense mechanism interacts with the disease.

Reprogramming SREBP1-dependent lipogenesis and inflammation in high-risk breast with licochalcone A: a novel path to cancer prevention.

Anti-estrogens have had limited impact on breast cancer (BC) prevention. Novel agents with better tolerability, and efficacy beyond estrogen receptor (ER) positive BC are needed. We studied licochalcone A (LicA) for ER-agnostic BC prevention. We evaluated antiproliferative effects of LicA in seven breast cell lines and its suppression of ER+ and ER- xenograft tumors in mice. High-risk human breast tissue was treated with LicA ex vivo , followed by RNA sequencing and metabolism flux modeling. Confirmatory testing was performed in an independent specimen set and ER+/- BC cell lines using NanoString metabolic panel, proteomics, western blots, and spatiotemporally resolved cholesterol quantification in single cells. LicA suppressed proliferation in vitro and xenograft tumor growth in vivo . It downregulated pivotal steps in PI3K-AKT-SREBP1-dependent lipogenesis, suppressed PI3K and AKT phosphorylation, SREBP1 protein expression, and cholesterol levels in the plasma membrane inner leaflet, to the levels in normal breast cells. LicA also suppressed prostaglandin E2 synthesis and PRPS1-catalyzed de novo nucleotide biosynthesis, stalling proliferation; further evident by reduced MKI67 and BCL2 proteins. LicA targets SREBP1, a central regulator of lipogenesis and immune response, reducing pro-tumorigenic aberrations in lipid homeostasis and inflammation. It is a promising non-endocrine candidate for BC prevention.