Breast Cancer Prevention Research Articles

Implementation of polygenic risk scores in secondary prevention of (breast) cancer

Abstract Utilizing polygenic risk scores to inform secondary prevention of breast cancer via population screening programs is one of the pioneering applications of genomics in public health applications. Over the last decade, polygenic risk scores for breast cancer have been developed and validated in various European populations (AUC ± 0.63, OR per Z unit ± 1.6, depending on the population). In some countries, the polygenic risk score has been integrated with decision modeling tools, such as CanRisk in the Netherlands, and low-level implementation into health and care systems has started. Implementation strategies vary, but generally consider initial implementation into high-risk populations, such as breast cancer families, in specialized clinical setting, such as academic medical centres, or specialized cancer clinics, referring relatives of patients to population screening based on comprehensive risk modelling, including polygenic risk scores. This route may be followed by other disease fields as well. The presentations outlines the current evidence and considerations on breast cancer genetic risk modelling, clinical pilot studies and the outline of step-wise implementation of such models to benefit secondary prevention programs. We start from the perspective of a single hospital, to the needed steps to upscale to national populations, both in diversity of these populations, as the throughput of genetic testing and counselling, until the harmonization and recalibration of various European healthcare models. We draw from examples of the Genotyping on all patients (GOALL), building cancer health platforms (CanHeal) and Genome of Europe (GoE) consortia.

COMMUNITY EMPOWERMENT IN THE SADARI PROGRAM (BREAST SELF-EXAMINATION)

Background: Cancer is currently one of the leading causes of death worldwide. One of the most common cancers and with the highest incidence is breast cancer. There are still many PKK Mojosongo Jebres Surakarta mothers who are not aware of the importance of early breast examination. This Breast Self-Examination (BSE) has been proven to be culturally acceptable, religiously friendly, and inexpensive. BSE is one way of action to find early symptoms of breast cancer that can be detected by mothers themselves, does not require experts to find breast cancer early, and is part of prevention efforts. Objective: This community service is to improve BSE knowledge and skills through community empowerment which will have an impact on increasing awareness and efforts to prevent breast cancer in Mojosongo. Methods: This activity begins with a regional visit to find out the existing problems, and a meeting with the PKK Chairperson to coordinate the implementation, the sampling technique uses a total sampling of all PKK mothers totaling 50 people who are given education and practice on how to do self-examination at home. Results: Community service can improve the ability of PKK mothers to do BSE independently. Conclusion: SADARI Education and Training improves the ability of knowledge and skills independently and has a positive impact on maternal health. The Recommendations, need to encourage and follow up on education and training on SADARI examinations by adding periodic follow-up sessions, this is done so that knowledge and practice of SADARI continue to be implemented.

Knowledge and Misinformation About Breast Cancer Risk Factors, Symptoms, and Prevention Among Healthy and Affected Women: A Study on 2375 Italian Participants

Background: Breast cancer is the most common cancer among women worldwide and remains the leading cause of death among Italian women. Despite increased breast cancer awareness and improved diagnostic techniques, mortality rates remain high globally. In Italy, despite the availability of screening programs by the National Health System (NHS) for all Italian women aged 50–69 every two years, the participation rate remains relatively low. The low uptake of screening may be attributed to a lack of general cancer knowledge among women, including awareness of risk factors, symptoms, and prevention measures. This study investigates the knowledge and misinformation in a population of Italian women regarding breast cancer risk factors, symptoms, and prevention. Methods: From March 2021 to January 2022, we conducted a survey targeting the female population in Italy, with a total of 2375 participants willingly participating in the study. To investigate factors linked to variations in attitudes toward breast cancer, the participants were categorized into two groups: the general population (Group A, n = 2235) and women who have had or currently have breast cancer (Group B, n = 140). Statistically significant differences were identified between these two groups. Results: The findings revealed considerable confusion regarding both the symptoms and causes associated with cancer, as well as prevention measures. This confusion was particularly prominent among women in the general population and those with lower levels of education. Conclusions: Given these insights, it remains crucial to promote accurate health information concerning risk factors, symptoms, and prevention strategies related to this devastating disease, emphasizing the ongoing importance of disseminating correct health information.

How social class shapes breast cancer risk perspectives and prevention practices of Australian midlife women: a qualitative study using the concept of ‘breast cancer candidacy’

BackgroundThe increasing incidence of breast cancer and disease burden is a significant public health concern. While 30% of breast cancers could be prevented through addressing modifiable risk factors, misconceptions among women about breast cancer risks hamper primary prevention. In the absence of primary prevention, secondary prevention such as mammography increases the early detection of breast cancer and improves health outcomes. However, current population-level screening rates indicate secondary prevention is suboptimal. More effective public health efforts to improve breast cancer prevention are required. Given breast cancer is socially patterned, this work explores how social class impacts women’s breast cancer prevention practices. This study uses the concepts of lay epidemiology and candidacy as a mechanism to understand women’s breast cancer risk perspectives. It engages Bourdieu’s relational social class theory to unpack how women’s social, cultural, and structured life contexts shape these perspectives and their considerations regarding primary and secondary prevention.MethodsIn this qualitative study 43 Australian midlife women (aged 45–64 years), were interviewed to explore their understandings of breast cancer risks, how they perceived their own risk, and how this shaped their prevention behaviours. A theory-informed thematic analysis applying Bourdieu’s concepts of habitus, capital, and fields to understand how women’s social class positions shapes risk perspectives and prevention practices was conducted.ResultsThis social class analysis showed differences in how women engage in breast cancer discourse, consider risks, and participate in breast cancer prevention. Middle-class women prioritise health promoting practices and were more likely than working-class and affluent women to attend mammography screening. Working-class women experience structural factors, like low income, stress and difficult life circumstances, which hamper primary prevention practices and for some screening is not considered or prioritised, and their decisions not to screen are less active. Affluent women often do not consider themselves at-risk due to their healthier ‘lifestyles. ’They suggest that this, and their knowledge of screening benefits and harms allows them to make informed decisions not to screen.ConclusionsWomen interpret and understand breast cancer risks differently and enact prevention practices within the parameters afforded by their social class positions. These findings are useful to inform improved public health approaches regarding both modifiable breast cancer risks and increasing mammography screening. To improve equity in breast cancer prevention efforts, such approaches must respond to limitations based on social class and address structural factors that impact prevention practices.

Anticancer potentiality of Hottentotta saulcyi scorpion curd venom against breast cancer: an in vitro and in vivo study.

Scorpion venom may include pharmacological substances that have the potential to provide benefits. Multiple scientific investigations have shown that particular scorpion venoms induce apoptosis and inhibit the development of cancerous cells. The present study investigated the potential anticancer properties of the crude venom derived from Hottentotta saulcyi (H. saulcyi) on both in vivo mice models and in vitro breast carcinoma cells. The venom of scorpions belonging to the species H. saulcyi was obtained with the application of electrical stimulation at voltages of 8 and 10V. The determination of the Average Lethal Dose 50 (LD50) was conducted. The present work assessed the in vitro cytotoxicity and morphological characteristics of H. saulcyi venom using fluorescence microscopy, MTT assay, and flow cytometry assessment. Additionally, research was performed to assess the cytotoxic effects in vivo on a mouse model with breast cancer. The examination of MCF-7 cells treated with scorpion venom at a microscopic level revealed the existence of cells undergoing apoptosis. The venom of H. saulcyi has anticancer properties, as shown by the observation that MCF-7 cells had a 62.12% apoptotic rate when exposed to a dose of 1.47mg/L. Based on the results obtained, it can be shown that the viability of MCF-7 cells has exhibited a substantial reduction (P < 0.01). Furthermore, the findings indicated that the venom of H. saulcyi resulted in a significant increase in the synthesis of TNF-α, IL-6, IL-10, TGF-β, and caspase (P < 0.05). The treatment groups administered with H. saulcyi venom exhibited a significant augmentation in the expression of proapoptotic genes compared to the control group of healthy individuals. The transcription of the BCL2 gene exhibited a statistically significant increase in the healthy control group compared to both the healthy venom-treated group (P < 0.05) and the malignant venom-treated group (P < 0.01). The crude venom of H. saulcyi has considerable promise in demonstrating anticancer properties. Further investigation may be warranted to explore the potential of using H. saulcyi crude venom as a medicinal platform for the prevention of breast cancer.

Integrated analysis of microbiota and gut microbial metabolites in blood for breast cancer.

Gut microbiota and associated metabolites have been linked to breast carcinogenesis. Evidences demonstrate blood microbiota primarily originates from the gut and may act as a biomarker for breast cancer. We aimed to characterize the microbiota-gut microbial metabolites cross-talk in blood and develop a composite diagnostic panel for breast cancer. We performed 16S rRNA gene sequencing and metabolomics profiling on blood samples from 107 breast cancer cases and 107 age-paired controls. We found that the alpha diversity of the blood microbiota was decreased in breast cancer compared to controls. There were significantly different profiles of microbiota and gut microbial metabolites in blood between these two groups, with nine bacterial genera and four gut microbial metabolites increased in patients, while thirty-nine bacterial genera and two gut microbial metabolites increased in controls. Some breast cancer-associated gut microbial metabolites were linked to differential blood microbiota, and a composite microbiota-metabolite diagnostic panel was further developed with an area under the curve of 0.963 for breast cancer. This study underscored the pivotal role of microbiota and gut microbial metabolites in blood and their interactions for breast carcinogenesis, as well as the potential of a composite diagnostic panel as a non-invasive biomarker for breast cancer.IMPORTANCEOur integrated analysis demonstrated altered profiles of microbiota and gut microbial metabolites in blood for breast cancer patients. The extensive correlation between microbiota and gut microbial metabolites in blood assisted the understanding of the pathogenesis of breast cancer. The good performance of a composite microbiota-gut microbial metabolites panel in blood suggested a non-invasive approach for breast cancer detection and a novel strategy for better diagnosis and prevention of breast cancer in the future.

The p53/miRNA Axis in Breast Cancer.

One of the main health issues in the modern world is cancer, with breast cancer (BC) as one of the most common types of malignancies. Different environmental and genetic risk factors are involved in the development of BC. One of the primary genes implicated in cancer development is the p53 gene, which is also known as the "gatekeeper" gene. p53 is involved in cancer development by interacting with numerous pathways and signaling factors, including microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that regulate gene expression by binding to the 3' untranslated region of target mRNAs, resulting in their translational inhibition or degradation. If the p53 gene is mutated or degraded, it can contribute to the risk of BC by disrupting the expression of miRNAs. Similarly, the disruption of miRNAs causes the negative regulation of p53. Therefore, the p53/miRNA axis is a crucial pathway in the progression or prevention of BC, and understanding the regulation and function of this pathway may contribute to the development of new therapeutic strategies to help treat BC.

Bridging the knowledge gap: educational needs of Iranian women for virtual breast cancer prevention: a qualitative study

BackgroundBreast cancer prevention is a globally significant and cost-effective public health priority, particularly in low- and middle-income countries. Empowering women through improved health literacy is a key strategy for reducing the disease burden. However, effective educational programs must be tailored to the specific cultural context and needs of the target community. This study explored the educational needs of Iranian women for a virtual breast cancer prevention program.MethodsA descriptive qualitative design was used from January to July 2022. Purposive sampling with maximum variation was utilized to recruit a sample of 28 participants. Data collection was conducted through semi-structured interviews. Following the method outlined by Graneheim and Lundman, qualitative content analysis was employed to analyze the interview data. MAXQDA 2020 software was used for data analysis. Components of trustworthiness, including credibility, dependability, confirmability, and transferability, were considered.ResultsOur findings identified three primary categories: “developing women’s scientific, practical, and attitudinal capabilities”; “features of program content”; and “principles of electronic content design”. These results offer valuable insights into the educational needs of Iranian women for virtual breast cancer prevention programs.ConclusionsTo design an effective virtual program, it is crucial to address all three domains: cognitive, emotional, and psychomotor. Program content should be organized and presented using methods that sensitize women to the importance of breast cancer prevention and motivate them to participate. Furthermore, the program’s design should be grounded in evidence-based practices and principles of electronic content design, ensuring cultural sensitivity to the needs of Iranian women.

Unraveling the metastasis-preventing effect of miR-200c in vitro and in vivo.

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR-200c) can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear whether miR-200c expression alone is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR-200c expression in MDA-MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs, including lung, liver, brain, and spleen, revealed a dramatically reduced metastatic burden in mice with miR-200c-expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR-200c on collective- and single-cell migration in vitro, utilizing MDA-MB 231 and MCF7 cell systems with genetically modified miR-200c expression. Analysis of collective-cell migration revealed confluence-dependent motility of cells with altered miR-200c expression. Additionally, scratch assays showed an enhanced predisposition of miR-200c-negative cells to leave cell clusters. The in-between stage of collective- and single-cell migration was validated using transwell assays, which showed reduced migration of miR-200c-positive cells. Finally, to measure migration at the single-cell level, a novel assay on dumbbell-shaped micropatterns was performed, which revealed that miR-200c critically determines confined cell motility. All of these results demonstrate that sole expression of miR-200c impedes metastasis formation in vivo and migration in vitro and highlights miR-200c as a metastasis suppressor in breast cancer.

The Influence of Microbiota on Breast Cancer: A Review

Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast tissue, its changes during cancer progression, and its considerable impact on both the tumor microenvironment (TME) and the tumor immune microenvironment (TIME). We extensively analyze how the microbiota influences cancer growth, invasion, metastasis, resistance to drugs, and the evasion of the immune system, with a special focus on its effects on the TIME. Furthermore, we investigate distinct microbial profiles associated with the four primary molecular subtypes of breast cancer, examining how the microbiota in tumor tissues compares with that in adjacent normal tissues. Emerging studies suggest that microbiotas could serve as valuable diagnostic and prognostic biomarkers, as well as targets for therapy. This review emphasizes the urgent need for further research to improve strategies for breast cancer prevention, diagnosis, and treatment. By offering a detailed examination of the microbiota’s critical role in breast cancer, this review aims to foster the development of novel microbiota-based approaches for managing the disease.

EFEITO DA CASTRAÇÃO NO DESENVOLVIMENTO DE NEOPLASIAS MAMÁRIAS EM CADELAS – REVISÃO DE LITERATURA

Breast neoplasia is considered the second most common neoplasm. Affects domestic animals, with the main diagnosis being in female dog, which can affect females aged between approximately 7 and 12 years, however it can also be seen in young animals, and then even related to the sexual and hormonal integrity of the bitch. Breast tumors can manifest in different ways and stages, which varies according to the type of tumor (neoplastic or not), affected cell and degree of aggressiveness, where generally 68.4% of breast tumors diagnosed in dogs are malignant. The aim of this work is to review the effects of ovariohysterectomy performed in domestic females in what is said respect to the development of breast neoplasms, aiming to bridge the processes pathophysiological 1 involved, such as particularities of the estrous cycle in bitches, administration of contraceptives, environmental and endogenous factors of the animal itself, corresponding age and predisposed breeds, clarifying the importance of procedure for both the prevention of breast cancer in bitches, as well as other illnesses.

Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.

Recent studies suggested fine particulate matter (PM2.5) exposure increases the risk of breast cancer, but evidence among racially and ethnically diverse populations remains sparse. Among 58,358 California female participants of the Multiethnic Cohort (MEC) Study followed for an average of 19.3 years (1993-2018), we used Cox proportional hazards regression to examine associations of time-varying PM with invasive breast cancer risk (n = 3,524 cases; 70% African American and Latino females), adjusting for sociodemographics and lifestyle factors. Subgroup analyses were conducted for race and ethnicity, hormone receptor status, and breast cancer risk factors. Satellite-based PM2.5 was associated with a statistically significant increased incidence of breast cancer (hazard ratio [HR] per 10 μg/m3, 1.28 [95% CI, 1.08 to 1.51]). We found no evidence of heterogeneity in associations by race and ethnicity and hormone receptor status. Family history of breast cancer showed evidence of heterogeneity in PM2.5-associations (Pheterogeneity = .046). In a meta-analysis of the MEC and 10 other prospective cohorts, breast cancer incidence increased in association with exposure to PM2.5 (HR per 10 μg/m3 increase, 1.05 [95% CI, 1.00 to 1.10]; P = .064). Findings from this large multiethnic cohort with long-term air pollutant exposure and published prospective cohort studies support PM2.5 as a risk factor for breast cancer. As about half of breast cancer cannot be explained by established breast cancer risk factors and incidence is continuing to increase, particularly in low- and middle-income countries, our results highlight that breast cancer prevention should include not only individual-level behavior-centered approaches but also population-wide policies and regulations to curb PM2.5 exposure.

Conscious Techniques Affected the Adolescent’s Ability In Early Breast Cancer Detection

Breast cancer is a malignant tumor and grows in the breast tissue resulting in death. Breast cancer prevention by means of breast self-examination. This study aimed to determine the effect of video media on conscious techniques with a combination of demonstrations on the practical ability of adolescents in early detection of breast cancer. The method used a quasi-experimental design, non-equivalent control group design with a population of 279 and a sample of 40 respondents with inclusion criteria of young women, aged 16 years as students of SMA Negeri 1 Tarik Sidoarjo. The data collection measured skills in 2 groups of respondents. The experimental intervention group used videos and demonstrations, while the intervention control group used lectures and leaflets. The intervention was done in 1 day, the posttest was conducted 7 days after the intervention. The results showed that the average value of the pretest posttest of the two groups increased. The results of the statistical test paired T-Test obtained a significant value of p-value = (0.000 &lt; 0.05) meant that there was an effect of providing video media with conscious techniques with a combination of demonstrations on the practical ability of adolescents in early detection of breast cancer. Educators should develop programs to improve skills for early detection of breast cancer, in collaboration with health workers through health promotion so that all students are aware of health.

Transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor initiation in Neu/Erbb2 transgenic mice.

Although significant progress in the treatment of breast cancer has been achieved, toxic therapies would not be required if breast cancer could be prevented from developing in the first place. While breast cancer prevention is difficult to study in humans due to long disease latency and stochastic cancer development, transgenic mouse models with 100% incidence and defined mammary tumor onset, provide excellent models for tumor prevention studies. In this study, we used Neu/Erbb2 transgenic mice (MTB-TAN) as a model of human HER2+ breast cancer to investigate whether a family of microRNAs, known as the miR-200 family, can prevent mammary tumor development. Overexpression of Neu induced palpable mammary tumors in 100% of the mice within 38 days of Neu overexpression. When the miR-200b/200a/429 cluster was co-overexpressed with Neu in the same mammary epithelial cells (MTB-TANba429 mice), the miR-200b/200a/429 cluster prevented Neu from inducing mammary epithelial hyperplasia and mammary tumor development. RNA sequencing revealed alterations in the extracellular matrix of the mammary gland and a decrease in stromal cells including myoepithelial cells in Neu transgenic mice. Immunohistochemistry for smooth muscle actin confirmed that mammary epithelial cells in control and MTB-TANba429 mice were surrounded by a layer of myoepithelial cells and these myoepithelial cells were lost in MTB-TAN mice with hyperplasia. Thus, we have shown for the first time that elevated expression of miR-200 family members in mammary epithelial cells can completely prevent mammary tumor development in Neu transgenic mice possibly through regulating myoepithelial cells.

7426 Tamoxifen-Induced Ovarian Hyperstimulation in a Pre-Menopausal Patient with Breast Cancer History: Spontaneous Resolution with Conservative Management

Abstract Disclosure: S. Gondi: None. M. Contento: None. A. Leiter: None. Background: Tamoxifen is a selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors (ER) on tumors and inhibits the effect of estrogen, which is used in the treatment and prevention of ER-positive breast cancer. Tamoxifen therapy has been reported to increase serum estrogens and cause ovarian hyperstimulation in premenopausal women, but knowledge on how to manage these conditions is limited. Clinical Case: A 36-year-old pre-menopausal female with history of malignant neoplasm of the right breast (ER positive) who completed neoadjuvant chemotherapy, lumpectomy, and radiation, on tamoxifen for seven years presented with new-onset oligomenorrhea. Laboratory testing done by the patient’s gynecologist revealed total estrogen 2,723 pg/mL (reference range [RR] 34-501), testosterone 132 ng/dL (RR 8-60), anti-Mullerian hormone 12.7 ng/mL (RR for age 0.66-8.75), ovulation-phase follicle stimulating hormone 11.5 mIU/mL (RR 4.7-21.5) and luteinizing hormone (LH) 63.3 mIU/mL (RR 14-95.6). Further workup revealed that ovarian tumor markers alpha-fetoprotein and serum human chorionic gonadotropin and other labs including dehydroepiandrosterone sulfate, progesterone 17-OH, lactate dehydrogenase, prolactin, and thyroid stimulating hormone were normal. Transvaginal ultrasound (TVUS) showed a new 2.8 x 1.9 x 2.3 cm complex left ovarian cyst, which, along with the elevated estrogen level, was concerning for ovarian hyperstimulation. Treatment with LH-releasing hormone (LHRH) agonists, surgical consultation, and discontinuation of tamoxifen were offered as potential management strategies, but the patient opted for observation and continued tamoxifen. Two months later, estradiol was 989 pg/mL (RR 85-498), and then three months later decreased to 152 pg/mL with repeat TVUS showing resolution of the left ovarian cyst. The patient’s oligomenorrhea resolved with resumption of regular menstrual cycles. Conclusion: While it is well-known that tamoxifen causes elevated serum estrogen levels and can lead to ovarian hyperstimulation, there is limited research on the management of these side effects. Treatment strategies in past cases have included oophorectomy or medical management with LHRH agonists or gonadotropin-RH agonists. However, this case demonstrates that a tamoxifen-induced ovarian cyst and high estrogen levels can resolve on its own with continued tamoxifen treatment. Conservative management with monitoring via imaging and repeat estrogen levels may be sufficient in management of pre-menopausal women with tamoxifen-induced ovarian hyperstimulation. Presentation: 6/1/2024

6550 National Statin Prescription Trends in Patients With Breast Cancer and Diabetes for Primary Cardiovascular Disease Prevention

Abstract Disclosure: A.B. Yang: None. G. Mhango: None. C. Kong: None. J.J. Lin: None. J.P. Wisnivesky: Consulting Fee; Self; Sanofi, Banook, PPD. Grant Recipient; Self; Sanofi, Regeneron Pharmaceuticals, Axella, Arnold Consultants. A. Leiter: None. Background: Cardiovascular disease (CVD) is the leading cause of death in older early-stage breast cancer (BC) survivors. Due to cardiotoxic BC treatments such as chemotherapy and radiation, patients with BC and diabetes (DM) are at increased risk of CVD. In patients with BC and DM, statins decrease CVD mortality. Since 2013, many clinical guidelines broadened statin indications for primary CVD prevention in patients with DM, making &amp;gt;85% of patients eligible. Little is known about statin prescription (Rx) patterns in older BC survivors with DM, a group at high risk of CVD. Hypothesis: We hypothesized that statin Rxs increased over time, but were less likely in BC survivors with more advanced locoregional BC and lower comorbidity burden. Methods: A population-based, retrospective cohort study was conducted using Surveillance, Epidemiology and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting DM who were diagnosed with stage 0-III primary BC between 2008-17. We excluded patients with prior CVD who died &amp;lt;1 year after BC diagnosis. Statin Rx (atorvastatin, pravastatin, rosuvastatin, simvastatin, fluvastatin, lovastatin) was defined as ≥1 statin pharmacy claim &amp;lt;1 year after BC diagnosis. Comorbidity burden was assessed with a modified Charlson Comorbidity Index (CCI). We compared patient demographic and clinical characteristics by statin Rx status using the chi-square test. Using a multivariate logistic regression adjusting for age, race, CCI, BC stage, and diagnosis year, independent predictors of statin Rx were identified. Results: Of 8,423 BC patients with pre-existing DM, 5,698 (68%) had a statin Rx. Statin Rx increased over time (BC diagnosis year 2008-10: 66%, 2011-13: 66%, 2014-15: 69%, 2016-17: 70%; p=0.01) and differed by age (66-69: 66%, 70-74: 70%, 75-79: 69%, ≥80: 65%; p&amp;lt;0.01) and race (White: 68%, Black: 62%, Latinx: 66%, Other: 72%; p&amp;lt;0.01). Statin Rx did not differ by comorbidity burden (CCI 0: 68%, 1-2: 67%, ≥3: 67%; p=0.87) and declined with higher BC stage (0: 73%, I: 70%, II: 65%, III: 63%; p&amp;lt;0.01). In adjusted analyses, more recent BC diagnosis (2016-17 vs. 2008-10: odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.04-1.38), age group (70-74 vs. 66-69: OR: 1.24, 95% CI: 1.09-1.41), race (Black vs. White: OR 0.77, 95% CI: 0.66-0.89) and higher BC stages (II vs. 0: OR: 0.76, 95% CI: 0.58-1.00; III vs. 0: OR: 0.72, 95% CI: 0.54-0.97) remained predictors of statin Rx. Conclusions: In a nationally representative cohort analysis of older early-stage BC patients, statin Rx increased between 2008-17 and varied by age, race, and BC stage. Elucidating gaps in statin Rx can potentially improve guideline-concordant Rx in a group at high risk for CVD and reduce disparities. Presentation: 6/2/2024

Cysteine protease I29 propeptide from Calotropis procera R. Br. As a potent cathepsin L inhibitor and its suppressive activity in breast cancer metastasis.

Breast cancer metastasis is associated with a poor prognosis and a high rate of mortality. Cathepsin L (CTSL) is a lysosomal cysteine protease that promotes tumor metastasis by degrading the extracellular matrix. Gene set enrichment analysis revealed that CTSL expression was higher in tumorous than in non-tumorous tissues of breast cancer patients and that high-level CTSL expression correlated positively with the epithelial-mesenchymal transition. Therefore, we hypothesized that inhibiting CTSL activity in tumor cells would prevent metastasis. In this study, we characterized the inhibitory activity of SnuCalCpI15, the I29 domain of a CTSL-like cysteine protease from Calotropis procera R. Br., and revealed that the propeptide stereoselectively inhibited CTSL in a reversible slow-binding manner, with an inhibitory constant (Ki) value of 1.38 ± 0.71 nM, indicating its potency as an exogenous inhibitor in anti-cancer therapy. SnuCalCpI15 was localized intracellularly in MDA-MB-231 breast cancer cells and suppressed tumor cell migration and invasion. These results demonstrate the potential of SnuCalCpI15 as a novel agent to prevent breast cancer metastasis.

Traditional Chinese Medicine Herbs for Breast Cancer Prevention and Survival: A Narrative Review of Epidemiological Studies from Taiwan.

This review aims to describe the association of integrating traditional Chinese medicine (TCM) herbs into conventional medicine (CM) in preventing breast cancer and improving survival rates among breast cancer patients of Taiwan. Of 7 relevant studies, spanning 2014-2023, 4 investigated breast cancer risk in women with menopausal symptoms and other comorbidities. All 4 reported that TCM herbal use was associated with lower risks of developing breast cancer. Three studies investigated survival in newly-diagnosed breast cancer patients receiving CM. All reported that adjunctive TCM users had lower mortality rates than CM-only patients. However, the heterogeneity of study designs, populations, and interventions may limit the generalizability and robustness of the findings. TCM herbs may promote breast cancer prevention and survival when used alongside CM. More rigorous observational research and clinical trials in specific patient populations are needed to guide clinical decision-making.

Association between dietary factors and breast cancer risk: a matched case-control study in Vietnam

BackgroundThe role of diet in breast cancer prevention is controversial and limited in low-middle-income countries (LMICs). This study aimed to investigate the association between different dietary factors and breast cancer risk in Vietnamese women.MethodsThree hundred seventy newly histologically confirmed breast cancer cases and 370 controls matched by 5-year age from September 2019 to March 2020 in Ho Chi Minh City were recorded dietary intake using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated using conditional logistic regression and adjusted with potential confounders.ResultsCompared to the lowest quartile of intake, we found that the highest intake of vegetables, fruit, soybean products, coffee, and egg significantly decreased breast cancer risk, including dark green vegetables (OR 0.46, 95% CI 0.27-0.78, ptrend=0.022), legumes (OR 0.19, 95% CI 0.08-0.44, ptrend <0.001), starchy vegetables (OR 0.37, 95% CI 0.21-0.66, ptrend=0.003), other vegetables (OR 0.46, 95% CI 0.28-0.77, ptrend=0.106), fruits (OR 0.44, 95% CI 0.26-0.74, ptrend <0.001), soybean product (OR 0.45, 95% CI 0.24-0.86, ptrend=0.311), coffee (OR 0.47, 95% CI 0.23-0.95, ptrend 0.004), and egg (OR 0.4, 95% CI 0.23-0.71, ptrend=0.002).ConclusionGreater consumption of vegetables, fruit, soybean products, coffee, and eggs is associated with a lower risk of breast cancer. This study provides evidence of breast cancer prevention by increasing the intake of these dietary groups, especially in LMICs.

Clinical Pharmacology Of Selective Oestrogen Receptor Modulators In The Prevention Of Breast Cancer, Osteoporosis, Coronary Heart Disease, Alzheimer's Disease, Use In Hormone Replacement Therapy, Cholesterol Metabolism

Oestrogen is the key regulatory hormone for the development and maintenance of reproductive functions and affects various physiological systems, including the skeletal, cardiovascular, and central nervous systems. oestrogen replacement therapy (ERT) is highly effective in postmenopausal women, addressing menopausal symptoms and providing beneficial effects on osteoporosis and coronary heart disease. However, ERT is associated with significant side effects, such as an increased risk of breast cancer. To mitigate these risks, selective oestrogen receptor modulators (SERMs) have been developed. SERMs are a growing class of synthetic nonsteroidal compounds that act as oestrogen receptor agonists or antagonists in a tissue-specific manner. They can selectively activate or inhibit oestrogen receptors in different tissues throughout the body. SERMs are used to treat a variety of conditions, including ER-positive breast cancer, osteoporosis, coronary heart disease, Alzheimer’s disease, and cholesterol metabolism disorders in postmenopausal women. Specific SERMs are employed for different conditions: raloxifene for osteoporosis, tamoxifen and toremifene for breast cancer, clomiphene for the induction of ovulation, and ormeloxifene for oral contraception. Arzoxifene is used for altering cholesterol metabolism. Each SERM forms a unique complex with oestrogen receptors, influencing target tissues and resulting in a tissue-selective pharmacological profile. This unique mechanism of action translates into specific safety and efficacy profiles for each SERM. The surprising pharmacology of SERMs has sparked interest in developing new selective medications, allowing for precise treatment of various diseases. This article reviews the pharmacological properties of SERMs and explains how they differ from oestrogen in their actions.