Use Of Chemopreventive Agents Research Articles

Immunoprevention Strategies for Colorectal Cancer in Lynch Syndrome Carriers.

The immune revolution that swept the field of oncology in the mid-2010s with the advent of checkpoint inhibitors has led to a paradigm shift in approaches toward adapting new cancer prevention modalities. Cancer vaccines have emerged from this era with astounding potential as a durable intervention to prevent cancers especially for patients with hereditary susceptibilities such as Lynch syndrome carriers. This review covers new insights in the immunoprevention landscape for patients living with Lynch syndrome including highlights ranging from clinical trials exploring the use of chemoprevention agents to boost immune cellularity to investigative studies using novel vaccine approaches to induce long-term antitumor immunity.

Chemoprevention of Head and Neck Cancer: A Review of Current Approaches and Future Perspectives.

Head and neck squamous cell carcinoma (HNSCC) is a spectrum of heterogeneous malignancies. A variety of genetic, environmental, and lifestyle factors contribute to the development of HNSCC. Carcinogenesis is a multistep process in which cell proliferation-associated oncogenes and cell-cycle regulation-associated tumor suppressor genes are dysregulated, resulting in premalignant lesions. Immune evasion is a critical step in the progression of benign lesions to advanced cancer. This review discusses the advances that have been made in chemoprevention strategies for HNSCC. The rationale for the use of chemopreventive agents to inhibit head and neck cancer development is highlighted by the positive outcomes of several clinical trials. We discuss the potential of some of the commonly studied agents including vitamin A analogs, EGFR inhibitors, COX-2 inhibitors, metabolic modulators, and natural compounds such as green tea, as well as immunotherapy and photodynamic therapy to prevent HNSCC. Our review provides insight into the potential benefits of these agents and the gaps that remain to be addressed. The published results reaffirm the promise of chemoprevention in head and neck cancer and suggest that continued exploration is needed to overcome the limitations. Because the current focus on chemopreventive agents is limited, major efforts in precision oncology approaches and substantial increase in funding will promote research into chemoprevention, which will eventually decrease the incidence of HNSCC.

A cytotoxicity and mechanistic investigation of mono- and di-chloro naphthalenes

Polychlorinated naphthalenes (PCNs) were characterized as persistent organic pollutants (POPs) that were widely distributed in the environment. Although the striking in vivo toxicity of these pollutants towards both animals and humans was well documented, their cytotoxicity and mechanism of action have not been extensively investigated. In this study, the in vitro antiproliferative activity of mono- and di-chloronaphthalenes as representative PCNs were evaluated and the results indicated strong growth inhibitory effects against mammalian cells, especially the human breast MCF-10A cell and human hepatic HL-7702 cells. 2-Chloronaphthalene with the most potent antiproliferative effects within the tested PCNs, which showed IC50 values ranging from 0.3 mM to 1.5 mM against selected human cell lines, was investigated for its working mechanisms. It promoted cellular apoptosis of MCF-10A cells upon the concentration of 200 μM. It also induced the autophagy of MCF-10A cells in a dose-dependent manner, resulting in cell death via the interaction of autophagy and apoptosis. Thus, these findings supported the theoretical foundation for interventional treatment of PCNs toxicity and also provided implications for the use of chemopreventive agents against the toxic chlorinated naphthalenes in the environments.

Updated Perspectives on the Diagnosis and Management of Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome marked by extensive colorectal polyposis and a high risk of colorectal cancer (CRC). Having access to screening and enrollment programs can improve survival for patients with FAP by enabling them to undergo surgery before the development of colorectal cancer. Provided that there are a variety of surgical options available to treat colorectal polyps in patients with adenomatous polyposis, the appropriate surgical option for each patient should be considered. The gold-standard treatment to reduce this risk is prophylactic colectomy, typically by the age of 40. However, colectomy is linked to morbidity and constitutes an ineffective way at preventing extra-colonic disease manifestations, such as desmoid disease, thyroid malignancy, duodenal polyposis, and cancer. Moreover, extensive studies have been conducted into the use of chemopreventive agents to prevent disease progression and delay the necessity for a colectomy as well as the onset of extracolonic disease. The ideal chemoprevention agent should demonstrate a biologically plausible mechanism of action and provide safety, easy tolerance over an extended period of time and a lasting and clinically meaningful effect. Although many pharmaceutical and non-pharmaceutical products have been tested through the years, there has not yet been a chemoprevention agent that meets these criteria. Thus, it is necessary to develop new FAP agents that target novel pathways, such as the mTOR pathway. The aim of this article is to review the prior literature on FAP in order to concentrate the current and future perspectives of diagnosis and treatment. In conclusion, we will provide an update on the diagnostic and therapeutic options, surgical or pharmaceutical, while focusing on the potential treatment strategies that could further reduce the risk of CRC.

Chemoprevention in Inherited Colorectal Cancer Syndromes.

Cancer prevention in hereditary gastrointestinal predisposition syndromes relies primarily on intensive screening (e.g., colonoscopy) or prophylactic surgery (e.g., colectomy). The use of chemopreventive agents as an adjunct to these measures has long been studied both in the general population and in hereditary cancer patients, in whom the risk of malignancy, and therefore the potential risk reduction, is considerably greater. However, to date only few compounds have been found to be effective, safe, and tolerable for widespread use. Furthermore, many of the studies involving these rare syndromes suffer from small sample sizes, heterogeneous patient cohorts, short follow-up duration, and lack of standardized endpoints, creating challenges to draw generalizable conclusion regarding efficacy. The following review summarizes the current data on various chemopreventive compounds used in Lynch syndrome and familial adenomatous polyposis in addition to several agents that are currently being investigated.

Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.

Natural Products as Cancer Chemo Preventive Agents: Where We Stand

This work briefly reviews cancer chemoprevention. This is a very challenging field, as products with a high level of toxicity such as chemotherapeutic agents may be proposed and accepted only under life-threatening conditions. Cancer chemoprevention is otherwise limited to completely safe substances, preferably having neither toxic nor side effects, administered in relatively low amounts. Phases of clinical trials, therapeutic end-points, and biomarkers of chemoprevention are difficult to be defined. The clinical trials needed to prove the efficacy of chemopreventive agents must be very long and extremely widespread to achieve significance, with many variables difficult to control, and therefore subjected to many confounding factors. This makes them almost impossible. It is, therefore, no surprise, if the progress of chemoprevention has been so far very limited. There are only a few examples of direct use of chemopreventive agents, under investigation, but with anything but established protocols, in addition to indirect uses such as general supplementation with antioxidant, anti-inflammatory, and immune-supportive agents. Cancer chemoprevention remains a potentially very rewarding approach, certainly worth further study, but extremely difficult to pursue, in need of different methodological approaches to producing valuable chemopreventive compounds of clear dosages and benefits.

Resveratrol as a Chemopreventive Agent in Lung Cancer Therapy

For decades, lung cancer has been the most widespread cancer in the world and the leading cause of cancer death. Lung malignancy is the superior cause of death in Indonesia, accompanying the second topmost number of new cases. The low survival rate of lung cancer patients reflects the therapy's low success rate due to side effects and cancer cells' resistance to chemotherapy and radiotherapy. Combination therapy, which includes the use of chemopreventive agents, can reduce the risk of side effects and resistance. Natural product-based chemopreventive agents used together with accompanying chemical anti-cancer drugs and/or actinotherapy can overcome cancer cell resistance, improve therapy effectiveness, and reduce side effects. Resveratrol is a compound belonging to the non-flavonoid polyphenolic group contained, particularly in vine fruits, berries, and some nuts. Resveratrol exhibits anti-cancer activity, according to considerable in vitro and in vivo studies, and hence has what it takes to be reasonably applied as a chemopreventive compound. The discovery of resveratrol's chemopreventive mechanism against lung cancer is expected to enable the development of a chemopreventive compound that can be used together with accompanying chemical anti-cancer drugs and/or actinotherapy.

Effectiveness of Prophylactic Use of Hepatoprotectants for Tuberculosis Drug-Induced Liver Injury: A Population-Based Cohort Analysis Involving 6,743 Chinese Patients.

Background: Tuberculosis drug-induced liver injury (TB-DILI) is a common and potentially severe adverse drug reaction leading to treatment interruption and treatment failure. The real-world preventive effectiveness of hepatoprotective agents for DILI is not well described. The aim of the study was to evaluate the patterns of prophylactic therapies in real-world settings and risks of DILI among adult TB patients without known risk factors for DILI. Methods: This is a population-based retrospective cohort study of patients receiving first-line anti-tuberculosis drugs in the Chinese Center for Disease Control and Prevention (CDC) TB registry linked to the Ningbo Regional Health Care Database (NRHCD) between 2015 and 2020. The primary exposure was any use of chemopreventive agents including silymarin and/or glycyrrhetinic acid during the 30-day period prior to TB diagnosis (index date). The main outcome measure was the occurrence of newly onset DILI following TB treatment. Eligible patients were followed until the earliest of any DILI, treatment discontinuation, death, or end of the study period (30 June 2020). Marginal structural competing risk models and Cox models via inverse probability treatment weights using high-dimensional propensity scores were used to estimate subdistribution hazard risks (SHR) and 95% confidence intervals (CIs) for DILI risks, with adjustment for age, sex, TB-related characteristics, and comorbidities. Results: We identified a cohort of 6,743 adult patients with TB (mean age of 47.1 [SD 18.7] years; 65.80% male), of whom 2,886 (42.8%) patients received hepatoprotective agents. A total of 895 DILI events and 111 all-cause death events without DILI were observed over a median follow-up of 367 days post-TB diagnosis. The incidence rates of composite outcomes combining DILI and all-cause mortality were 248.9 and 222.3 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.35, 95% CI 1.11–1.64), respectively. The incidence rates of DILI were 223.7 and 196.1 per 1,000 person-years in the hepatoprotective agent exposed and unexposed groups (relative hazard ratio 1.38, 95% CI 1.12–1.71), respectively. Patients with any chemopreventive agent use had comparable liver function changes as evidenced by laboratory tests. Conclusion: A non-trivial number of adult patients received chemopreventive agents for TB-DILI. However, prophylactic utilization of hepatoprotective agents was not associated with a reduction in TB-DILI risks.

Progress in Drug and Formulation Development for the Chemoprevention of Oral Squamous Cell Carcinoma: A Review

Cancer is a life-threatening global problem with high incidence rates. Prioritizing the prevention of cancer, chemopreventive agents have drawn much attention from the researchers. This review focuses on the discussion of the progress in the development of chemopreventive agents and formulations related to the prevention of oral cancer. In this perspective, an extensive literature survey was carried out to understand the mechanism, control and chemoprevention of oral cancer. Different patented agents and formulations have also exhibited cancer preventive efficacy in experimental studies. This review summarizes the etiology of oral cancer and developments in prevention strategies. The growth of oral cancer is a multistep activity necessitating the accumulation of genetic as well as epigenetic alterations in key regulatory genes. Many risk factors are associated with oral cancer. Genomic technique for sequencing all tumor specimens has been made available to help detect mutations. The recent development of molecular pathway and genetic tools has made the process of diagnosis easier, better forecast and efficient therapeutic management. Different chemical agents have been studied for their efficacy to prevent oral cancer and some of them have shown promising results. Use of chemopreventive agents, either synthetic or natural origin, to prevent carcinogenesis is a worthy concept in the management of cancers. Preventive measures are helpful in controlling the occurrence or severity of the disease. The demonstrated results of preventive agents have opened an arena for the development of promising chemopreventive agents in the management of oral squamous cell carcinoma.

Breast Cancer Prevention: Current Approaches and Future Directions.

The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease. Current strategies to decrease a woman's risk of developing breast cancer include primary prevention, such as avoiding tobacco, exogenous hormone use and excess exposure to ionizing radiation, maintaining a normal weight, exercise, breastfeeding, eating a healthy diet and minimizing alcohol intake. Chemoprevention medications are available for those at high risk, though they are underutilized in eligible women. Mastectomy and/or bilateral oophorectomy are reasonable strategies for women who have deleterious mutations in genes that dramatically increase the risk of developing cancer in either breast. There are a variety of strategies in development for the prevention of breast cancer. Personalized approaches to prevent breast cancer that are being developed focus on advances in precision medicine, knowledge of the immune system and the tumor microenvironment and their role in cancer development. Advances in our understanding of how breast cancer develops are allowing investigators to specifically target populations who are most likely to benefit. Additionally, prevention clinical trials are starting to evaluate multi-agent cancer prevention approaches, with the hope of improved efficacy over single agents. Finally, there is a push to increase the use of chemopreventive agents with proven efficacy, such as tamoxifen and raloxifene, in the prevention of breast cancer.

Prostate cancer chemoprevention by natural agents: Clinical evidence and potential implications

Prostate cancer (PCa) is the most common non-skin cancer and the second leading cause of cancer-related deaths in American men. Due to its long latency period, PCa is considered as an ideal cancer type for chemopreventive interventions. Chemopreventive agents include various natural or synthetic agents that prevent or delay cancer development, progression and/or recurrence. Pre-clinical studies suggest that many natural products and dietary agents have chemopreventive properties. However, a limited number of these agents have been tested in clinical trials, with varying success. In this review, we have discussed the available clinical studies regarding the efficacy of natural chemopreventive agents against PCa, including tea polyphenols, selenium, soy proteins, vitamins and resveratrol. We have also provided a discussion on the clinical challenges and opportunities for the potential use of chemopreventive agents against PCa. Based on available literature, it appears that the variable outcomes of the chemopreventive clinical studies necessitate a need for additional studies with more rigorous designs and methodical interpretations in order to measure the potential of the natural agents against PCa.

Cancer chemoprevention - selected molecular mechanisms.

The effect of diet on cancer formation and prevention of carcinogenesis has attracted considerable attention for years and is the subject of several studies. Some components of the daily diet, such as resveratrol, curcumin, genistein, gingerol, can significantly reduce the risk of cancer or affect the rate of tumor progression. Cancer chemoprevention assumes the use of natural or synthetic biologically active substances in order to prevent, inhibit or reverse the progression of cancer. There are many biologically active compounds in several natural products, i.e. garlic, ginger, soy, curcuma, tomatoes, cruciferous plants or green tea. Their chemopreventive activity is based on the inhibition of processes underlying carcinogenesis (inflammation, transformation and proliferation), but also affects the final phase of carcinogenesis - angiogenesis and metastasis. Despite the relatively low toxicity of chemopreventive agents, their molecular targets often coincide with the objectives of the currently used cancer therapies. The widespread use of chemopreventive agents may contribute to reduction of the rate of cancer incidence, and increase the effectiveness of conventional cancer therapies. In the present study, selected molecular mechanisms of the chemopreventive activity have been discussed, especially their involvement in the regulation of signal transduction, cell cycle regulation, apoptosis, metastasis and angiogenesis. The role of chemopreventive agents in the inflammatory process, the metabolism of xenobiotics and multidrug resistance has been also characterized.

Chemoprevention in African American Men with Prostate Cancer

Recommendations for cancer screening are uncertain for the early detection or prevention of prostate cancer in African American men. Thus, chemoprevention strategies are needed to specifically target African American men. The evidence was examined on the biological etiology of disparities in African Americans related to prostate cancer. Possible chemopreventive agents and biomarkers critical to prostate cancer in African American men were also studied. High-grade prostatic intraepithelial neoplasia may be more prevalent in African American men, even after controlling for age, prostate-specific antigen (PSA) level, abnormal results on digital rectal examination, and prostate volume. Prostate cancer in African American men can lead to the overexpression of signaling receptors that may mediate increased proliferation, angiogenesis, and decreased apoptosis. Use of chemopreventive agents may be useful for select populations of men. Green tea catechins are able to target multiple pathways to address the underlying biology of prostate carcinogenesis in African American men, so they may be ideal as a chemoprevention agent in these men diagnosed with high-grade prostatic intraepithelial neoplasia.

Chemoprevention of colorectal neoplasia.

Colorectal cancer is a common and often fatal malignancy. Currently, the modifications that alter disease outcome include early symptom recognition, population screening as well as improved surgical and adjuvant treatments. Preventative strategies have been limited with little evidence that lifestyle changes significantly alter risk. There is however a growing awareness of a potential role for chemoprevention in some patient groups. This study aimed to review the literature associated with chemoprevention in colorectal cancer. An electronic literature search of MEDLINE and Embase databases was performed on PubMed for studies detailing the use of chemoprevention agents in colon and rectal cancer. The search was limited to clinical trials on adult humans (>16 years of age) published in English since 1990. The strongest evidence is for non-steroidal anti-inflammatory drugs slowing polyp progression, notably Sulindac and aspirin in patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respectively. There is also increasing evidence that continuing use of low-dose aspirin reduces long-term incidence of colorectal cancers. Cyclooxygenase 2 inhibitors also have a potential role but cardiac toxicity currently limits their use. Folic acid, statins, antioxidants, calcium and 5-aminosalicylic acid lack evidence to support their use at present. Currently, there is not enough evidence to support the implementation of a chemopreventative agent for general use. However, there appears to be a role for aspirin in selected subgroups.

Abstract B68: Explanatory models of risk: The role of social context in breast cancer risk perception and decision making

Abstract Background: The current practice of counseling high-risk breast cancer patients using probabilistic risk estimates has not proven to be effective in engaging women, with less than 1% of eligible women participating in medical interventions to reduce breast cancer risk. Further, studies show that racial and ethnic minority women are under-represented in breast cancer prevention clinical trials (Cyrus-David, 2006), and they are less likely than whites to be aware of, discuss, or take chemoprevention agents (Kaplan et al., 2006). This study seeks to describe how a diverse group of women use explanatory models of risk to describe perceptions of breast cancer risk and make decisions about risk-reducing behaviors. Methods: 30 in-depth, qualitative interviews were collected at two US academic hospitals as part of a National Surgical Adjuvant Breast and Bowel Project mixed-methods study to oversample for racial and ethnic minorities. Women identified to have an elevated risk of developing breast cancer were interviewed following risk counseling with a medical provider. A thematic analysis informed by grounded theory methods was conducted. The explanatory model framework (Kleinman, 1978) guided formation of codes around explanatory model topic areas (etiology, symptoms, pathophysiology, course of illness, and treatment). These explanatory model codes were supplemented with inductive codes developed through open coding related to beliefs about cancer, risk, health, and social context. Results: Two key themes were identified as closely linked to women's explanatory models of risk: ‘risk perception’ and ‘control over risk’. These perceptions of risk and control were used to identify patterns in how women chose to manage their risk for breast cancer. Whether women had high or low perceptions of risk and control affected the ways in which they used explanatory models to describe their decisions. For example, women with perceptions of high risk and high control all discussed their social network as influential in modeling how they could reduce their own risk. These women adopted a variety of behaviors to gain control over risk, ranging from diet and exercise changes to the use of chemoprevention agents. Conversely, women with perceptions of high risk and low control based decisions much more closely on their general explanatory models of health, falling back on established philosophies in their decision-making. Women who opted for chemoprevention agents in this group discussed their philosophy of decision making as dependent on physician recommendations. How women interpreted ‘symptoms’ of risk was also essential to women's descriptions of their participation in risk-reduction behaviors. Those women who perceived their risk to be high interpreted symptoms such as ADH, ALH, or LCIS as a disease that required medical intervention. On the other hand, women with perceptions of low risk interpreted these symptoms as in the normal course of bodily changes, contrasting with information provided by physicians suggesting an increased risk for breast cancer. Discussion: There are important differences in how women use explanatory models of risk that contribute to the adoption of medical interventions. Risk counseling must address patient explanatory models, which influence both perceptions of risk and control over risk. These perceptions subsequently influence the ways in which women describe their decisions about participating in risk-reducing behaviors. New approaches are needed to address patient beliefs and perceptions about risk and prevention for breast cancer. Failing to acknowledge the experiences of patients threatens to marginalize minority groups from preventive care. Citation Format: Christine M. Gunn, Barbara Bokhour, Tracy A. Battaglia, Sarah Blakeslee, Christine Holmberg. Explanatory models of risk: The role of social context in breast cancer risk perception and decision making. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B68.

The evolving role of nonsteroidal anti-inflammatory drugs in colon cancer prevention: a cause for optimism.

Colorectal cancer (CRC) is a serious yet preventable disease. The low acceptance and cost of colonoscopy as a screening method or CRC make chemoprevention an important option. Nonsteroidal anti-inflammatory drugs (NSAIDs), not currently recommended for CRC prevention, have the potential to evolve into the agents of choice for this indication. Here, we discuss the promise and challenge of NSAIDs for this chemopreventive application.Multiple epidemiologic studies, randomized clinical trials (RCTs) of sporadic colorectal polyp recurrence, RCTs in patients with hereditary colorectal cancer syndromes, and pooled analyses of cardiovascular-prevention RCTs linked to cancer outcomes have firmly established the ability of conventional NSAIDs to prevent CRC. NSAIDs, however, are seriously limited by their toxicity,which can become cumulative with their long-term administration for chemoprevention, whereas drug interactions in vulnerable elderly patients compound their safety. Newer, chemically modified NSAIDs offer the hope of enhanced efficacy and safety.Recent work also indicates that targeting earlier stages of colorectal carcinogenesis, such as the lower complexity aberrant crypt foci, is a promising approach that may only require relatively short use of chemopreventive agents. Drug combination approaches exemplified by sulindac plus difluoromethylornithine appear very efficacious. Identification of those at risk or most likely to benefit from a given intervention using predictive biomarkers may usher in personalized chemoprevention. Agents that offer simultaneous chemoprevention of diseases in addition to CRC, e.g., cardiovascular and/or neurodegenerative diseases,may have a much greater potential for a broad clinical application.

Trends in the Cost-effectiveness of Chemoprevention for Breast Cancer—2001 to 2015

Breast cancer is the most commonly diagnosed cancer among US women and costs of treatment are estimated to be over $16.5 billion annually. The use of chemopreventive agents for the primary prevention of breast cancer has been an available option for women at high risk for breast cancer since 1998, however, uptake has been low. Cost-effectiveness analyses are used to determine whether a given intervention will be beneficial for a specific population while maintaining costs below a standard threshold for health systems. A number of cost-effectiveness analyses on the use of the chemopreventive drugs, tamoxifen and raloxifene, among women at high risk for breast cancer have been published over the past 15 years. These studies have used diverse methodologies to determine which, if any, high-risk women would benefit from the use of chemoprevention. The results of these cost-effectiveness analyses have been highly varied, with about half finding that chemoprevention is cost-effective for women who meet high-risk criteria for breast cancer. The sparse literature available in this field highlights the need for a more comprehensive analysis of the cost-effectiveness of chemoprevention that takes into account the most recently available information on costs and outcomes.

Current paradigms of cancer chemoprevention

Cancer chemoprevention has been continually evolving ever since the term was coined in the 70s. From the original approaches of identifying chemopreventive agents from the dietary constituents based on the epidemiological data to the current status of adapting them from the molecular targets, significant understanding of cancer as a disease and its possible prevention has been achieved. The identification of the chemopreventive agent from a complex mixture of natural product extracts involves numerous steps including bioassay guided fractionation; evaluation of the extracts, fractions and isolated new chemicals selectively using in vitro and in vivo experimental models; and understanding the mechanism of their action. This in turn provides identification of the molecular target for the parent drug and a basis for the synthesis of more effective, nontoxic analogs. A chemopreventive agent by definition needs to be nontoxic, since it is expected to be consumed by healthy people that may be at a higher risk of developing cancer. This makes a case for these agents to be evaluated as possible adjuvant chemotherapeutic agents. It is expected that more selective delivery methods to the target organs to eliminate toxicity and use of chemopreventive agents as adjuvant chemotherapeutic agent using personalized approaches will be the next steps for chemoprevention.

Abstract P5-13-05: Richer and wiser: Factors correlated with chemoprevention use in the United States

Abstract Introduction: Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer by up to 50%, yet the uptake of these agents remains poor. We sought to determine factors associated with chemoprevention uptake in a nationally representative sample. Methods: The National Health Interview Survey (NHIS) is a population-based survey conducted annually by the CDC and is designed to be representative of the non-institutionalized civilian population in the United States. We utilized data from the 2010 NHIS cancer supplement to determine factors associated with chemoprevention uptake in women ≥ 35 years of age. Statistical analyses were conducted using SUDAAN software. Results: In 2010, 10,959 women ≥ 35 years of age were surveyed, representing 83,377,082 people in the population. Of these, 0.21% reported taking chemoprevention, using either tamoxifen or raloxifene. On bivariate analyses, factors correlating with chemoprevention uptake included age, race/ethnicity, education, insurance, income and geographic region (see Table). Interestingly, MRI use, family history of premenopausal breast cancer in first degree relatives, and personal risk perception were not associated with chemoprevention use. On multivariate analysis, education and income remained independent predictors of chemoprevention use. Conclusion: Approximately 0.2% of women take chemoprevention. It is concerning that sociodemographic factors of education and income are independent predictors of the use of chemopreventive agents for breast cancer, while risk perception and family history do not seem to correlate with uptake rates. These findings are a call to action for improved education and counseling of those who are at greatest risk, and highlight potential disparities in access to appropriate chemoprevention across all sociodemographic groups. Bivariate and Multivariate Analyses of Factors Correlated with Chemoprevention UptakeFactorBivariate AnalysisMultivariate Analysis Chemoprevention (%)No Chemoprevention (%)p-valueOR (95% CI)p-valueAge 0.0481 0.1087< 40 yr3.2211.93 1.00 40-49 yr5.8726.11 0.78 (0.05-12.44) 50-59 yr11.7024.88 1.44 (0.10-21.43) 60-69 yr23.8218.54 3.15 (0.32-31.41) 70-79 yr44.4110.77 8.62 (0.78-94.75) 80+ yr10.997.77 1.53 (0.10-23.66) Race/ethnicity 0.0006 0.8372Hispanic3.9011.06 00.81 (0.11-5.85) White96.1071.63 1.00 Black011.80 - Asian04.61 - Other00.89 - Education 0.0371 <0.0001< Grade 127.1214.15 1.00 High School25.8627.73 1.86 (0.35-9.75) Some college/Assoc21.4229.97 1.85 (0.36-9.45) Bachelors15.5917.49 1.44 (0.13-16.35) Masters11.708.37 3.23 (0.41-25.14) Prof/Doctorate18.302.28 25.22 (4.30-147.87) Insurance 0.0002 0.0686Not covered012.44 - Medicare72.6129.38 1.00 Medicaid3.224.50 2.38 (0.22-26.15) Military01.74 - Private24.1751.94 0.28 (0.06-1.26) Income 0.0005 0.0306<$35K32.3934.53 1.00 $35K-$74,99926.1131.53 0.97 (0.21-4.42) $75K-$99,999012.08 - $100K+41.6021.86 3.78 (0.94-15.22) Region 0.0441 0.1649Northeast27.9318.62 1.00 Midwest31.6022.88 0.92 (0.32-2.64) South34.4935.66 0.65 (0.21-2.04) West5.9822.84 0.16 (0.03-0.86) Oophorectomy40.1115.160.08132.17 (0.77-6.09)0.1404MRI use2.315.170.2597 Family History2.315.130.2601 Risk Perception 0.1451 High41.5212.50 Average25.8947.49 Low32.5940.01 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-05.