Cancer Prevention Research Articles

Legislative review and recommendations for improving sun protection in schools.

Sun exposure in schools can account for a large portion of childhood sun exposure before the age of 20 years, yet legislation in the United States is lacking to properly protect children. Schools serve as a foundational resource to introduce and implement sun-safe practices in the youth population. Federal and state legislation relating to the access of sunscreen, sun-protective apparel, and shade was reviewed via the website LegiScan.com. At the time of publication, only 25 states have legislation in place that addresses and allows sunscreen to be used in school, given its classification as an over-the-counter medication. No state has implemented legislation allowing sunglasses to be worn in school, and only two states have laws explicitly allowing hats and other sun-protective apparel at schools. In addition, the provision of shade is addressed in four states. With a significant portion of sun exposure occurring at schools, state and federal legislation must address sun protection for students, opening the door for expanded access and additional research related to skin cancer prevention.

Harmonization of clinical practice guidelines for primary prevention and screening: actionable recommendations and resources for primary care

BackgroundClinical practice guidelines (CPGs) synthesize high-quality information to support evidence-based clinical practice. In primary care, numerous CPGs must be integrated to address the needs of patients with multiple risks and conditions. The BETTER program aims to improve prevention and screening for cancer and chronic disease in primary care by synthesizing CPGs into integrated, actionable recommendations. We describe the process used to harmonize high-quality cancer and chronic disease prevention and screening (CCDPS) CPGs to update the BETTER program.MethodsA review of CPG databases, repositories, and grey literature was conducted to identify international and Canadian (national and provincial) CPGs for CCDPS in adults 40–69 years of age across 19 topic areas: cancers, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, hepatitis C, obesity, osteoporosis, depression, and associated risk factors (i.e., diet, physical activity, alcohol, cannabis, drug, tobacco, and vaping/e-cigarette use). CPGs published in English between 2016 and 2021, applicable to adults, and containing CCDPS recommendations were included. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and a three-step process involving patients, health policy, content experts, primary care providers, and researchers was used to identify and synthesize recommendations.ResultsWe identified 51 international and Canadian CPGs and 22 guidelines developed by provincial organizations that provided relevant CCDPS recommendations. Clinical recommendations were extracted and reviewed for inclusion using the following criteria: 1) pertinence to primary prevention and screening, 2) relevance to adults ages 40–69, and 3) applicability to diverse primary care settings. Recommendations were synthesized and integrated into the BETTER toolkit alongside resources to support shared decision-making and care paths for the BETTER program.ConclusionsComprehensive care requires the ability to address a person’s overall health. An approach to identify high-quality clinical guidance to comprehensively address CCDPS is described. The process used to synthesize and harmonize implementable clinical recommendations may be useful to others wanting to integrate evidence across broad content areas to provide comprehensive care. The BETTER toolkit provides resources that clearly and succinctly present a breadth of clinical evidence that providers can use to assist with implementing CCDPS guidance in primary care.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

ObjectiveElucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.DesignWe performed single-cell transcriptome analysis on 230 ...

Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

Herbal Alternatives for Oral Health: Mechanistic Exploration with their Market Potential

The utilization of customary methods for oral cleanliness maintenance has a long-written history. Herbs are making a comeback all over the world. Herbal extracts have been used in dentistry to alleviate pain as antimicrobial plaque specialists, to delay receptor arrival, and as germicides, cancer prevention agents, antimicrobials, antifungals, antibacterial, antiviral, and analgesics. Current article gives an outline of different natural products used in oral care with their impacts on oral health, restorative actions, applications, and marketed products. This article also highlights mechanistic need of oral cleanliness and the different dental diseases associated with it. The regular phytochemicals could offer a successful anti-microbial and address ways to deal with avoidance and restorative systems for different dental infections. There are different herbal formulations available on the market for oral care such as paste, mouthwash, gargles, gels, etc. creating need for awareness of consumers towards the herbal products. In these review, we have also discussed the commercial aspect of the herbal dental products along with assessment of side effects and toxicity of these herbs.

Androgen receptor: Structure, signaling, function and potential drug discovery biomarker in different breast cancer subtypes.

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC. AR exhibits different behaviors depending on the breast cancer molecular subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since AR positivity's prognostic and predictive value remains uncertain, it is difficult to identify and stratify patients who would benefit from AR-targeted therapies alone. Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.

Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial.

Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased pro-inflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS, NCT01327846) evaluated the neutralizing anti-IL-1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab vs those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL-1β blockade cooperating with CH mutations to modify the disease course.

Cancer control Co-benefits of the Climate-Related provisions in the American inflation reduction act.

The American Inflation Reduction Act (IRA) of 2022 contains climate-related provisions that may have significant implications for cancer control and prevention. This commentary assesses the potential co-benefits of the IRA for cancer control efforts, specifically policies and programs to reduce carcinogen exposure via air quality monitoring and air pollution reduction. Allocations through the IRA for air quality improvement, paired with its environmental justice provisions, holds promise for advancing cancer prevention by targeting resources to communities most susceptible to environmental hazards. Moreover, climate resilience measures dictated by the IRA are crucial for oncology professionals grappling with the dual challenges of climate change and cancer care. Climate-driven extreme weather events can exacerbate carcinogen exposure and disrupt access to cancer care, underscoring the need for resilient healthcare infrastructure. The IRA's provisions for clean energy incentives and infrastructure upgrades offer oncology care institutions opportunities to mitigate emissions and bolster resilience against climate-related disruptions, ultimately improving cancer outcomes. Climate-related initiatives funded by the IRA present a unique and timely avenue to advance equitable cancer control efforts. This commentary underscores the critical intersection between climate resilience policy and oncology care, highlighting the potential to promote a healthier and more resilient future for all.

Curcumin and its anti-colorectal cancer potential: From mechanisms of action to autophagy.

Colorectal cancer (CRC) development and progression, one of the most common cancers globally, is supported by specific mechanisms to escape cell death despite chemotherapy, including cellular autophagy. Autophagy is an evolutionarily highly conserved degradation pathway involved in a variety of cellular processes, such as the maintenance of cellular homeostasis and clearance of foreign bodies, and its imbalance is associated with many diseases. However, the role of autophagy in CRC progression remains controversial, as it has a dual function, affecting either cell death or survival, and is associated with cellular senescence in tumor therapy. Indeed, numerous data have been presented that autophagy in cancers serves as an alternative to cell apoptosis when the latter is ineffective or in apoptosis-resistant cells, which is why it is also referred to as programmed cell death type II. Curcumin, one of the active constituents of Curcuma longa, has great potential to combat CRC by influencing various cellular signaling pathways and epigenetic regulation in a safe and cost-effective approach. This review discusses the efficacy of curcumin against CRC in vitro and in vivo, particularly its modulation of autophagy and apoptosis in various cellular pathways. While clinical studies have assessed the potential of curcumin in cancer prevention and treatment, none have specifically examined its role in autophagy. Nonetheless, we offer an overview of potential correlations to support the use of this polyphenol as a prophylactic or co-therapeutic agent in CRC.

Identification of prognostic stemness-related genes in kidney renal papillary cell carcinoma

BackgroundKidney renal papillary cell carcinoma (KIRP) is the second most prevalent malignant cancer originating from the renal epithelium. Nowadays, cancer stem cells and stemness-related genes (SRGs) are revealed to play important roles in the carcinogenesis and metastasis of various tumors. Consequently, we aim to investigate the underlying mechanisms of SRGs in KIRP.MethodsRNA-seq profiles of 141 KIRP samples were downloaded from the TCGA database, based on which we calculated the mRNA expression-based stemness index (mRNAsi). Next, we selected the differentially expressed genes (DEGs) between low- and high-mRNAsi groups. Then, we utilized weighted gene correlation network analysis (WGCNA) and univariate Cox analysis to identify prognostic SRGs. Afterwards, SRGs were included in the multivariate Cox regression analysis to establish a prognostic model. In addition, a regulatory network was constructed by Pearson correlation analysis, incorporating key genes, upstream transcription factors (TFs), and downstream signaling pathways. Finally, we used Connectivity map analysis to identify the potential inhibitors.ResultsIn total, 1124 genes were characterized as DEGs between low- and high-RNAsi groups. Based on six prognostic SRGs (CCKBR, GPR50, GDNF, SPOCK3, KC877982.1, and MYO15A), a prediction model was established with an area under curve of 0.861. Furthermore, among the TFs, genes, and signaling pathways that had significant correlations, the CBX2-ASPH-Notch signaling pathway was the most significantly correlated. Finally, resveratrol might be a potential inhibitor for KIRP.ConclusionsWe suggested that CBX2 could regulate ASPH through activation of the Notch signaling pathway, which might be correlated with the carcinogenesis, development, and unfavorable prognosis of KIRP.

Identification of cuproptosis-related long non-coding RNA and construction of a novel prognostic signature for bladder cancer: An observational study.

Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan-Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA.

Selenoprotein P in a Rodent Model of Exercise; Theorizing Its Interaction with Brain Reward Dysregulation, Addictive Behavior, and Aging

Exercise promotes health and wellness, including its operation as a protective factor against a variety of psychological, neurological, and chronic diseases. Selenium and its biomarker, selenoprotein P (SEPP1), have been implicated in health, including cancer prevention, neurological function, and dopamine signaling. SEPP1 blood serum levels were compared with a one-way ANOVA between sedentary (SED), moderately exercised (MOD) [10 m/min starting at 10 min, increasing to 60 min], and high-intensity interval training (HIIT) exercised rats [30 min in intervals of 2-min followed by a 1-min break, speed progressively increased from 10 to 21 m/min]. HIIT rats showed significantly higher serum SEPP1 concentrations compared to MOD and SED. More specifically, HIIT exercise showed an 84% increase in SEPP1 levels compared to sedentary controls. MOD rats had greater serum SEPP1 concentrations compared to SED, a 33% increase. The results indicated that increased exercise intensity increases SEPP1 levels. Exercise-induced increases in SEPP1 may indicate an adaptive response to the heightened oxidative stress. Previous studies found a significant increase in dopamine D2 receptor (D2R) binding in these same rats, suggesting a potential association between SEPP1 and dopamine signaling during exercise. Modulating antioxidants like SEPP1 through personalized therapies, including exercise, has broad implications for health, disease, and addiction.

Cancer incidence and digital information seeking in Germany: a retrospective observational study

Awareness is vital for cancer prevention. US studies show a strong link between web searches and cancer incidence. In Europe, the relationship remains unclear. This study characterizes regional and temporal relationships between cancer incidence and web searches and investigates the content of searches related to breast, cervical, colorectal, lung, prostate, and testicular cancer, brain tumors, and melanoma in Germany (July 2018–December 2019). Aggregate data from Google Ads Keyword Planner and national cancer registry data were analyzed. Spearman’s correlation coefficient (rS) examined associations between cancer incidence and web search, repeated measures correlation (rrm) assessed time trends and searches were qualitatively categorized. The frequency of malignancy-related web searches correlated with cancer incidence (rS = 0.88, P = 0.007), e.g., breast cancer had more queries than the lower-incidence cervical cancer. Seasonally, incidence and searches followed similar patterns, peaking in spring and fall, except for melanoma. Correlations between entity incidence and searches (0.037 ≤ rrm ≤ 0.208) varied regionally. Keywords mainly focused on diagnosis, symptoms, and general information, with variations between entities. In Germany, web searches correlated with regional and seasonal incidence, revealing differences between North/East and South/West. These insights may help improve prevention strategies by identifying regional needs and assessing impact of awareness campaigns.

Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.

Cytokines, including interleukin-12 (IL-12), are proteins that regulate cell survival, proliferation, differentiation, and function. IL-12 is a heterodimeric proinflammatory cytokine. It possesses tumoricidal properties and promotes M1 macrophage polarization and IFN-γ production by T helper (Th1) cells, which in turn stimulates the antitumor cytotoxic cluster of eight positive (CD8+) and natural killer cells, therefore activating an effector immune response against tumor cells. Herein, the IL-2 levels of 60 patients with generalized chronic periodontitis (GCP) were assessed. Plaque index, gingival index, pocket probing depth, bleeding on probing percentage (BOP %), and clinical attachment loss were the clinical indicators reported. Patients with GCP in the pretreatment group had substantially lower mean IL-12 levels than those in the post-treatment group. Short-term, nonsurgical treatment (NST) considerably improved periodontal indices and increased IL-12 levels, thereby reducing oral cancer risk. NST is a cost-effective and accessible cancer prevention procedure for general dentists.

Aspirin Metabolites and Mammographic Breast Density in Premenopausal Women.

Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. We, therefore, investigated the associations of aspirin metabolites, with MBD in premenopausal women. We performed this study on 705 premenopausal women who had fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least squares means of volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) by quartiles of aspirin metabolites (salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid). Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than non-users, but only mean peak area of salicyluric glucuronide increased by both dose (1-2 tabs per day=1,140,663.7, and ≥3 tabs per day=1,380,476.0) and frequency (days per week: 1 day=888,129.3, 2-3 days=1,199,897.9 and ≥4 days=1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV. Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of non-aspirin non-steroidal anti-inflammatory drug metabolites with MBD.

Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Abstract PO3-09-09: Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status

Abstract Introduction: Adherence to oral endocrine therapy (OET) for the prevention and treatment of hormone receptor-positive breast cancer (BC) is important as they reduce the risk of new or recurrent BC. OET adherence is greatly compromised in women of lower socioeconomic status (SES). We have recently reported that patients belonging to the African American race, with longer time on OET, and using OET in the prevention setting are more likely to be non-adherent to OET. Therefore, our study aims to design unique patient-centered interventions and pilot test their feasibility, acceptability, and effectiveness in improving OET adherence in African American women of low SES. Patients and Methods: This prospective study includes adult, African American women on OET for either the prevention or treatment of BC at Harris Health System in Houston, Texas, serving the underserved patient population with low SES. The first intervention is a motivational interviewing (MI) based telephone intervention consisting of an initial phone call followed by five monthly follow-up calls with an MI-trained pharmacy student. The second intervention is a theatre-based educational video with a script developed by a local African American playwright, featuring African American women. Three African American BC survivors with experience in taking OET consulted with the study team to convey their BC journey and explain challenges with taking OET. They provided feedback on the script and production of the educational video. Informed consent was obtained verbally via phone in the MI intervention and electronically for the educational video intervention. Individuals in both intervention groups were compensated with Walmart eGift cards. Pre- and post-intervention adherence was measured using the proportion of days covered (PDC) over 6-12 months and compared using a paired t-test. Participants also complete a survey at the end of the interventions to determine their acceptability. The survey responses were summarized descriptively. Results: For the MI intervention initiated in 20 patients, the median age and BMI of study participants was 61 years (range: 49-71) and 30.8 (range: 22.3-57.8) respectively. All participants identified their ethnicity as non-Hispanic or Latino. The majority of participants had hypertension (n=13, 65%) and/or hyperlipidemia (n=11, 55%) with depression (n=3, 15%) and diabetes (n=8, 40%) being less common. The most common stage of BC cancer was stage I (n=9, 45%), followed by stage II (n=4, 20%), stage 0 (n=3, 15%) and then stage III (n=2, 10%) and IV (n=2, 10%). Letrozole was the most common OET (n=13, 65%), followed by tamoxifen (n=3, 15%), anastrozole (n=2, 10%) and exemestane (n=2, 10%). Most participants were not on a CDK 4/6 inhibitor (n=18, 90%). The median number of years on therapy was 2.8 (0.6-4.5). The median pre-intervention PDC for OET was 0.7 (range: 0.2-0.9). The MI intervention is expected to be complete by October 2023 for all patients. For the educational video intervention, 7 out of the anticipated 25 participants have been enrolled in the intervention. All patients were taking OET for BC treatment and not prevention. Letrozole (n=3, 43%) and anastrozole (n=3, 43%) were the most utilized OET, followed by exemestane (n=1, 14%). While 5 participants (71%) in this intervention reported not missing any OET doses in the past week, 2 patients (29%) reported missing all 7 doses within the past week. After watching the educational video, most participants (n=6, 86%) reported that they strongly agreed to take their OET regularly. The recruitment of study participants for this intervention is ongoing. Conclusion: In this study, we report that MI and educational video interventions are feasible. The interventions and analysis of their effectiveness and acceptability are ongoing. Citation Format: Camille Johnson, Ann Adigwe, Nicole Ekezie, Bilqees Fatima, Zahra Majd, Keith Houk, Tejal Patel, Rob Shimko, Onyebuchi Ononogbu, Susan Abughosh, Meghana Trivedi. Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status [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 PO3-09-09.

Abstract PO5-11-11: Risk Assessment, Prevention and Early Detection of Breast Cancer Related Lymphedema – Objective Measurements and Patient Reported Outcomes

Abstract Background Breast cancer-related lymphedema (BCRL) affects the quality of life, but there is no consensus regarding early detection and monitoring. Patient-reported outcomes (PROs) are important in assessing cancer survivor outcomes, and different questionnaires have been developed. LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) and S-LYMPHA (Simplified LYMPHA) have reduced BCRL rates. This study aims to identify the most reliable PRO in a South Florida multi-ethnic population and to study correlations between PROs and objective measurements in the first 6 months after axillary surgery. Methods Patients undergoing axillary lymph node dissection (ALND) or axillary radiation were included. L-Dex score (Bioimpedance Spectroscopy) and three validated questionnaires (LyQLI, Lymphedema Quality of Life Inventory; LyQOL, Lymphedema Quality of Life and FACT-B4+ Functional Assessment of Cancer Therapy – Lymphedema) were recorded at baseline, and 6 months post-surgery to assess the agreement between patient-reported symptoms and BCRL. L-Dex score outside the normal range or a 10 unit increase above baseline was considered lymphedema. Additional variables such as demographics, tumor characteristics, and treatment modalities were recorded. Results Out of 40 recruited patients, 39 were analyzed (excluding one deceased patient). Patient and treatment characteristics are described in Table 1. Patients were divided into three cohorts (Figure 1) for analysis: ALND with no axillary radiation (7.69%; n=33), Sentinel Lymph Node Biopsy (SLNB) with axillary radiation (7.69 %; n=3), and ALND with axillary radiation (85%; n=3). In the first cohort, LYMPHA or S-LYMPHA were associated with lower rates of lymphedema (19% vs, 50%) (p=0.116). No patients in the second or third cohort developed lymphedema. There were 4 out of 20 (20%) patients with lymphedema with scores above the median for FACT B4+ (p= 0.480) and a lower score (higher quality of life) correlated with lower L-Dex (p=0.76). The higher value in the physical domain of LyQLI showed higher L-Dex (p=0.826). There was a significant inter-domain correlation in LyQLI and LyQOL (p= < 0.001). Conclusion These results validate the use of PROs alongside objective measurements to assess BCRL. In addition, LYMPHA and S-LYMPHA significantly reduce lymphedema rates. Larger numbers will be necessary to reach statistical significance and to identify the best PRO. Figure 1 Division of patient population into three cohorts Table 1 Demographic and Treatment Summary Citation Format: Anshumi Desai, Orli-Friedman Eldar, Gili Halfteck, Mecker Moller, Susan Kesmodel, Dido Franceschi, Neha Goel, Jessica Crystal, Laura Huang, Jennifer Hu, Koru-Sengal Tulay, Wei Zhao, Alexis Narvaez-Rojas, Eli Avisar. Risk Assessment, Prevention and Early Detection of Breast Cancer Related Lymphedema – Objective Measurements and Patient Reported Outcomes [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 PO5-11-11.

Abstract PS07-07: The RXR agonist, IRX4204, delays the formation of Brca1 mutant mammary tumors via modulation of the anti-tumor immune response

Abstract Background: Women with germline BRCA1 mutations are at an increased risk for developing breast cancer in their lifetime, often at a young age with more aggressive tumors. At present, prophylactic bilateral mastectomy is the most effective strategy for reducing breast cancer risk. However, this invasive procedure is irreversible and associated with potential complications. We and others have found that PARP inhibitors can delay Brca1-mutant tumor formation in mice and could be beneficial for the prevention of breast cancer. However, currently available PARP inhibitors are associated with modest toxicities that may not be acceptable to women without cancer. Thus, there remains an urgent need for the development of safe and effective therapies for the prevention of breast cancer. Here, we present data demonstrating the activity of IRX4204, a minimally toxic and highly specific agonist of the nuclear retinoid X receptor (RXR), to delay the formation of mammary tumors in a Brca1-deficient mouse model. This inhibitory effect on tumor growth is due, in part, to the role of IRX4204 in stimulating the anti-tumor immune response. Methods: We used the established MMTV-Cre, conditional Brca1 gene knockout, p53 heterozygous loss mouse model (BRCA1co/co; MMTV-Cre+/+; p53+/-) and selected for mutant female pups using PCR genotyping. At 16 weeks of age, all mice were separated into 4 treatment groups (n=10 per group): (1) sesame oil control; (2) the novel RXR agonist, IRX-4204 (10mg/kg); (3) high-dose IRX4204 (20 mg/kg); and (4) the RXR agonist, 9-cis-UAB-30 (5 mg/kg). All treatments were given by oral gavage five days per week, and mice were observed daily for tumor formation and toxicity. At the study endpoint, tumors and normal mammary glands were collected for additional analyses. Immunohistochemical staining was used to quantify CD8a, Ki-67 and cleaved caspase 3 expression in Brca1-deficient tumors. Oil Red O staining was used to measure changes in lipid accumulation in Brca1-deficient cell lines treated with IRX4204. qPCR was used to quantify the changes in gene expression of lipid metabolism-associated genes upon treatment with IRX4204 in vitro. Results: Vehicle-treated Brca1-deficient mice had a median time-to-tumor formation (TTF) of 211 days, with 100% developing tumors by 330 days. Mice treated with UAB 5 mg/kg had an improved median TTF of 261 days, whereas mice treated with IRX4204 10mg/kg or 20mg/kg had a median TTF of 347 and 304 days, respectively (p < 0.01). In addition, 60% of mice treated with IRX4204 10 mg/kg remained tumor-free at 330 days. IRX4204-treated tumors showed an increased infiltration of CD8-positive T-cells over vehicle-treated tumors (p < 0.05). Treatment of Brca1-deficient cell lines with IRX4204 in vitro resulted in a significant increase in lipid accumulation accompanied by a 2-fold increase of Srebf1 expression (a key transcription factor that regulates lipid homeostasis) within 24 hours of treatment (p < 0.05). Conclusion: These data demonstrate a novel use of the RXR agonist, IRX4204, to delay the formation of Brca1-deficient mammary tumors. We have found that IRX4204 treatment modulates the tumor immune response through increased infiltration of cytotoxic CD8-positive T-cells in Brca1-deficient mammary tumors in vivo. We have also determined that IRX4204 modulates lipid metabolism in breast cancer cell lines in vitro. It is known that lipid-derived antigens can stimulate T-cell activity. Our findings suggest that RXR agonists may alter lipid antigen production to activate an anti-tumor response. Additional immune and lipidomic studies are on-going. This work was supported by NCI-PREVENT grant (to PB and AM HHSN26100008) and CFP Foundation (Odyssey Fellowship to CM). Citation Format: Cassandra Moyer, Darian Coleman, Jamal Hill, Lana A. Vornik, Michelle Savage, Martin Sanders, Sei Shizuko, Altaf Mohammed, Powel Brown, Abhijit Mazumdar. The RXR agonist, IRX4204, delays the formation of Brca1 mutant mammary tumors via modulation of the anti-tumor immune response [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 PS07-07.