Study Of Tamoxifen And Raloxifene Research Articles

Abstract P5-13-02: Chemoprevention utilization in patients with a history of atypical hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in-situ: A retrospective chart review of patients diagnosed at an urban hospital with a large minority patient population

Abstract Background: The Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) trial showed that chemoprevention can reduce the risk of invasive breast cancer by nearly 50%. Despite these results, studies have shown that while an estimated 2 million women in the United States are eligible for chemoprevention, actual acceptance of these medications is low. Improving chemoprevention utilization rates hinges on better understanding current rates of utilization and factors affecting patient acceptance. Reported rates and barriers to chemoprevention use may not accurately reflect true utilization patterns in lower socioeconomic, minority patient populations. The aim of this IRB approved retrospective study was to characterize the rate and factors associated with chemoprevention use in patients with a diagnosis of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in-situ (LCIS) at an urban hospital with a high minority population. Methods – A retrospective chart review was performed for all diagnoses of ADH, ALH, and LCIS made at the University of Maryland Medical Center between the years 2005-2015. Concurrent DCIS or invasive cancer were excluded. Demographic and clinical information including age, race, education, GAIL score, BMI, and use of chemoprevention was recorded. Univariable and multivariable logistic regression were performed to identify factors associated with chemoprevention discussion and use. Results – 301 diagnoses of ADH/ALH/or LCIS were obtained and 127 women were eligible for analysis. The median age was 53 years old with 47% of patients being premenopausal. The majority were African-American (65%) and 51% had a high school degree or less. The median 5 year risk for developing breast cancer based on the GAIL model was 2.4%. The chemoprevention utilization rate for our patient population was 28% (n=34). Race, menopausal status, and breast density were not associated with chemoprevention discussion or use. We found that patients were more likely to have a chemoprevention discussion with their provider if they were older (p=0.03) or if they were referred to medical oncology (p<0.001, Fisher's exact test). Conclusions - Our study evaluated chemoprevention use in an understudied predominantly African-American patient population. We found a higher rate of chemoprevention utilization (28%) compared to previously reported rates. Age and medical oncology referral had a significant impact on provider-patient chemoprevention discussion. Though limited due to small sample size, our study nonetheless provided thought provoking results. Older patients may be at higher risk for developing breast cancer, however, it is important to consider that younger patients with risk factors may have a more favorable endocrine therapy benefit-risk ratio. In addition, our results highlight the importance of encouraging all physicians who are involved in women's' breast health to have a chemoprevention discussion with eligible patients, or for these physicians to refer patients to a medical oncologist for further discussion. Citation Format: DeRidder A, Mainor C, Goloubeva O, Ioffe O, Bellavance E, Tkaczuk K, Rosenblatt P. Chemoprevention utilization in patients with a history of atypical hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in-situ: A retrospective chart review of patients diagnosed at an urban hospital with a large minority patient population [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-13-02.

Raloxifene hydrochloride for breast cancer risk reduction in postmenopausal women

ABSTRACTIntroduction: Raloxifene is an estrogen receptor modulator which competes with estrogens for binding to the estrogen receptor. Based on the results of the STAR (Study of Tamoxifen And Raloxifene) trial, raloxifene has been approved by the U.S. Food and Drug Administration for the reduction of breast cancer (BC) risk in postmenopausal women at increased risk.Areas covered: This analysis reviews the activity of raloxifene and the clinical trials for non-BC indications which led to investigate its use as BC preventive agent. We review the trial establishing its efficacy for BC prevention and the meta-analyses including different SERMs for BC prevention.Expert commentary: Compared with tamoxifen, raloxifene has shown a slightly lower efficacy in reducing BC risk and a better safety profile. Raloxifene also offers to postmenopausal women a benefit in terms of osteoporosis. Future research should investigate its use in premenopausal women and in association with other preventive agents.

Gaining control over breast cancer risk: Transforming vulnerability, uncertainty, and the future through clinical trial participation - a qualitative study.

Concepts of disease risk and its management are central to processes of medicalisation and pharmaceuticalisation. Through a narrative perspective, this paper aims to understand how such macro-level developments may (or may not) be experienced individually, and how an algorithm that is used for recruitment into a clinical trial may structure individual notions of being 'at risk' and 'in need of treatment'. We interviewed 31 women participating in the Study of Tamoxifen and Raloxifene (STAR), a chemoprevention trial conducted in the US between 1999 and 2006. Interviews were thematically analysed. Women in the study had experienced the threat of breast cancer and felt vulnerable to developing the disease prior to STAR participation. The diagnosis of 'being at risk' for cancer through an algorithm that determined risk-eligibility for STAR, opened up the possibility for the women to heal. The trial became a means to recognise and collectivise the women's experiences of vulnerability. Through medication intake, being cared for by study coordinators, and the sense of community with other STAR participants, trial participation worked to transform women's lives. Such transformative experiences may nevertheless have been temporary, enduring only as long as the close links to the medical institution through trial participation lasted.

My Lived Experiences Are More Important Than Your Probabilities

Decision-making experts emphasize that understanding and using probabilistic information are important for making informed decisions about medical treatments involving complex risk-benefit tradeoffs. Yet empirical research demonstrates that individuals may not use probabilities when making decisions. To explore decision making and the use of probabilities for decision making from the perspective of women who were risk-eligible to enroll in the Study of Tamoxifen and Raloxifene (STAR). We conducted narrative interviews with 20 women who agreed to participate in STAR and 20 women who declined. The project was based on a narrative approach. Analysis included the development of summaries of each narrative, and thematic analysis with developing a coding scheme inductively to code all transcripts to identify emerging themes. Interviewees explained and embedded their STAR decisions within experiences encountered throughout their lives. Such lived experiences included but were not limited to breast cancer family history, a personal history of breast biopsies, and experiences or assumptions about taking tamoxifen or medicines more generally. Women's explanations of their decisions about participating in a breast cancer chemoprevention trial were more complex than decision strategies that rely solely on a quantitative risk-benefit analysis of probabilities derived from populations In addition to precise risk information, clinicians and risk communicators should recognize the importance and legitimacy of lived experience in individual decision making.

Final updated results of the NRG Oncology/NSABP Protocol P-2: Study of Tamoxifen and Raloxifene (STAR) in preventing breast cancer.

1500 Background: NSABP P-2 (STAR) was a randomized, double-blinded trial of tamoxifen vs raloxifene for the reduction of breast cancer incidence. The initial report from 2006 found raloxifene to be...

Breast cancer chemoprevention: little progress in practice?

Breast cancer chemoprevention: little progress in practice?

Abstract PL01-02: Smoking, molecular markers, and the risk of second cancers in cancer patients

Abstract Chemoprevention entails the reversal, prevention, abrogation or delay of carcinogenic progression to cancer (1). A number of successful trials have been conducted in the reversal of premalignancy in breast (2,3), prostate (4,5), and colorectal (6,7) cancer. In tobacco-related cancers, compelling evidence has suggested that ongoing tobacco smoking is able to prevent the reversal of premalignant lesions (8-10). The first such evidence was demonstrated by Lee et al. who noted that only those patients who ceased smoking saw meaningful improvement in their premalignancy in a randomized trial of 13-cis-retinoic acid in reversal of premalignancy (11). This built on the seminal work by Hong et al. who were able to show that high doses of vitamin A derivatives, specifically, 13-cis-retinoic acid, were able to reverse premalignancy in head and neck cancer (12), and perhaps more importantly, prevent or delay the development of second primary tumors while patients were on high dose 13-cis-retinoic acid (13). Unfortunately, the vast majority of patients on high dose 13-CRA or isotretinoin failed to tolerate this dose and required dose reduction or dose interruption (12,13). Subsequent randomized trials of 13-CRA in prevention of second primary tumors of the lung (14) and head and neck failed (15) to show the same promise as the higher dose, but one message was clearly consistent. Those patients who stopped smoking had considerably lower rates of second primary tumors and a trend toward a lower rate of primary lung or head and neck tumor recurrence (14, 15). Similar data emerged from the selenium trial, where the agent itself was ineffective in preventing second primary tumors of the lung, but those patients who were able to cease smoking had consistently lower rates of development of second primary tumors (16). A series of recent studies have indicated that genomic testing of patients on the 13-CRA head and neck second primary tumor prevention trial can select those patients who appear to derive the greatest benefit from chemopreventive approaches with natural compounds and their derivatives (17,18). These data suggest that patients with activation of the PI3-kinase/mTOR pathway are more likely to develop second primary cancers (18), consistent with data implicating this pathway demonstrated by Spira et al (19). Similarly, the Retinoid Head and Neck Second Primary Prevention Trial has shown data that certain patient populations on the head and neck second primary trial were more likely to benefit than others, based on genomic background, and that of their tumor (17,18). Thus, a strategy emerges whereby specific molecular markers, which are likely to predict benefit from second primary tumors, will be used to select future populations who are placed on chemopreventive approaches (20). However, one lesson must remain clear, and it must impact the future of all chemoprevention trials. Since smoking cessation, generally initiated by the patient, was the single most important factor in reducing secondary primary tumor risk, on these trials (14, 15, 21), all future such trials will require active smoking cessation efforts in these patient populations in order to achieve effective and active chemoprevention approaches. Such trials are planned and are necessary to undertake. The next generation of chemoprevention trials will involve CT screening studies, now the standard for those patients deemed at high risk for developing lung cancer (22, 23), and whether using inhibitors targeting inflammation (8-10) or metabolism (24), the inclusion of effective smoking cessation strategies in these chemopreventive trials is now a must. The overwhelming weight of the evidence therefore shows that effective development of approaches that integrate smoking cessation into biomarker-based chemoprevention of tobacco-driven cancers is no longer optional.

Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force

Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer. MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists. English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria. Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer. Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. Agency for Healthcare Research and Quality.

National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: Advancing the science of recruitment and breast cancer risk assessment in minority communities

One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. We have not addressed all identified barriers to the recruitment of minorities in clinical research. Our risk assessments and recruitment results do not reflect the modified Gail Model for African Americans. Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities. Incorporation of new information into models to improve the risk estimation of diverse populations should prove beneficial.

Baseline Mammographic Breast Density and the Risk of Invasive Breast Cancer in Postmenopausal Women Participating in the NSABP Study of Tamoxifen and Raloxifene (STAR)

Mammographic breast density is an established risk factor for breast cancer. However, results are inconclusive regarding its use in risk prediction models. The current study evaluated 13,409 postmenopausal participants in the NSABP Study of Tamoxifen and Raloxifene. A measure of breast density as reported on the entry mammogram report was extracted and categorized according to The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) classifications. An increased risk of invasive breast cancer was associated with higher mammographic breast density (P < 0.001). The association remained significant after adjusting for age, treatment, and smoking history [HR 1.35, 95% confidence interval (CI): 1.16-1.58], as well as when added to a model including the Gail score (HR 1.33, 95% CI: 1.14-1.55). At five years after random assignment, time-dependent area under the curve (AUC) improved from 0.63 for a model with Gail score alone to 0.64 when considering breast density and Gail score. Breast density was also significant when added to an abbreviated model tailored for estrogen receptor-positive breast cancers (P = 0.02). In this study, high BI-RADS breast density was significantly associated with increased breast cancer risk when considered in conjunction with Gail score but provided only slight improvement to the Gail score for predicting the incidence of invasive breast cancer. The BI-RADS breast composition classification system is a quick and readily available method for assessing breast density for risk prediction evaluations; however, its addition to the Gail model does not seem to provide substantial predictability improvements in this population of postmenopausal healthy women at increased risk for breast cancer.

Abstract 5444: In vitro modeling for breast cancer prevention - omega-3 ethyl esters functioning as preventive agents in 21T series models

Abstract Over the past few decades, multiple trials have warranted the benefits of using prevention as an effective strategy for lowering breast cancer incidence. The Breast Cancer Prevention Trial (BCPT) and Study of Tamoxifen and Raloxifene (STAR) conducted by National Cancer Institute demonstrated the effectiveness of tamoxifen and raloxifene as preventive agents in reducing diagnoses of invasive breast cancer. Another prevention study the VITAL cohort study demonstrated that omega-3 supplementation reduces breast cancer incidence in postmenopausal women. In vivo studies have produced results that demonstrated a delay in onset of breast cancer in transgenic mice model. However, current in vitro effort did not have a system that closely resembles the linear progression of breast cancer and therefore stalls the molecular investigation of breast cancer prevention. Majority of in vitro preventive studies have been conducted using cancer cell lines that do not represent precancerous status of mammary tissues and do not mirror the observation of delayed onset or reduced incidence in in vivo and clinical trials. A recent report has suggested the use of a new series of mammary cells that represent hyperplasia, ductal carcinoma in situ (DCIS) and invasive carcinoma in nude mice. In this study we propose the use of 21T series breast cancer cells as a model for breast cancer prevention study using omega-3 ethyl esters. Preliminary data using this model has shown that omega-3 ethyl esters derived from Omacor® reduce proliferation only in 21NT (DCIS) and 21MT-1 (Invasive Carcinoma) and not in 21PT cells (hyperplasic). Suppression of proliferation is most optimal in the presence of estrogen. Survival of cells is inhibited in all cell lines and Ki67 index is reduced in the presence of treatments. Targets of omega-3 ethyl esters may include Akt, ER and NF-kB. Current studies are conducted to investigate the effect of omega-3 ethyl esters on these targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5444. doi:1538-7445.AM2012-5444

Body Mass Index and the Risk for Developing Invasive Breast Cancer among High-Risk Women in NSABP P-1 and STAR Breast Cancer Prevention Trials

High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women.

Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR)

Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR)

Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR)

This study reports the gynecologic conditions in postmenopausal women (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of tamoxifen and raloxifene (STAR)/P-2 trial. This study, with a median follow-up period of 81 months, evaluated the incidence rates/risks of gynecologic conditions among women who were treated with tamoxifen and raloxifene. Compared with women who received tamoxifen therapy, women who received raloxifene therapy had a lower incidence of uterine cancer (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving tamoxifen therapy had more hot flashes (P < .0001), vaginal discharge (P < .0001), and vaginal bleeding (P < .0001). Our results suggest that tamoxifen has more of an estrogenic effect on the gynecologic reproductive organs. These effects should be considered in counseling women on options for breast cancer prevention.

Tamoxifen downregulation of miR-451 increases 14-3-3ζ and promotes breast cancer cell survival and endocrine resistance

Many estrogen receptor-positive breast cancers respond well initially to endocrine therapies, but often develop resistance during treatment with selective estrogen receptor modulators (SERMs) such as tamoxifen. We have reported that the 14-3-3 family member and conserved protein, 14-3-3ζ, is up-regulated by tamoxifen and that high expression correlated with an early time to disease recurrence. However, the mechanism by which tamoxifen up-regulates 14-3-3ζ and may promote the development of endocrine resistance is not known. Our findings herein reveal that the tamoxifen up-regulation of 14-3-3ζ results from its ability to rapidly down-regulate miR-451 that specifically targets 14-3-3ζ. The levels of 14-3-3ζ and miR-451 were inversely correlated, with 14-3-3ζ being elevated and miR-451 being at a greatly reduced level in tamoxifen-resistant breast cancer cells. Of note, down-regulation of miR-451 was selectively elicited by tamoxifen but not by other SERMs such as raloxifene or ICI182,780 (Fulvestrant). Increasing the level of miR-451 by overexpression, which decreased 14-3-3ζ, suppressed cell proliferation and colony formation, markedly reduced activation of HER2, EGFR, and MAPK signaling, increased apoptosis, and importantly, restored the growth inhibitory effectiveness of SERMs in endocrine-resistant cells. Opposite effects were elicited by miR-451 knock-down. Thus, we identify tamoxifen down-regulation of miR-451, and consequent elevation of the key survival factor 14-3-3ζ, as a mechanistic basis of tamoxifen-associated development of endocrine resistance. These findings suggest that therapeutic approaches to increase expression of this tumor suppressor-like microRNA should be considered to down-regulate 14-3-3ζ and enhance the effectiveness of endocrine therapies. Furthermore, the selective ability of the SERM tamoxifen but not raloxifene to regulate miR-451 and 14-3-3ζ may assist in understanding differences in their activities, as seen in the STAR breast cancer prevention trial and in other clinical trials.

Benefit/Risk Assessment for Breast Cancer Chemoprevention With Raloxifene or Tamoxifen for Women Age 50 Years or Older

The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents. Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo. Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks. We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.

Abstract SS01-01: View from the NCI: NCI's Division of Cancer Prevention

Abstract The Division of Cancer Prevention (DCP) was established in 1997 with the mission to plan and direct cancer prevention research including chemoprevention, nutritional science, genetic and infectious agent studies, early detection including biomarker development and validation, risk stratification, and biometry; and to coordinate community-based clinical research in cancer prevention and supportive care. Since then, there have been 42 new INDs and more than 200 publications about new prevention agents, including new classes of agents such as statins, HDAC inhibitors, NONSAIDs, p53 modulators and vaccines. One recent success is the finding that a combination of the anti-inflammatory sulindac and DFMO, pioneered by DCP, can reduce adenoma return by &amp;gt;95% reduction. In addition more than 50 early phase prevention trials have been conducted, expanding critical knowledge and stimulating science. More than one-third of all people in NCI's prevention, control, supportive care, and treatment trials enroll through DCP's Community Clinical Oncology Program (CCOP) network. The CCOP network initiated four large-scale phase III chemoprevention trials enrolling 87,560 participants over a 15-year period to establish the proof-of-principle that an agent can reduce a person's risk for developing cancer. Two of the trials resulted in the Food and Drug Administration drug approvals: tamoxifen and raloxifene for use in breast cancer risk reduction. A third agent, finasteride for use in prostate cancer risk reduction, is under consideration. The Early Detection Research Network, created in 2000 has made significant progress in: developing an organized effort for biomarker discovery and validation; building resources to support this effort; demonstrating the capabilities of several genomic and proteomic platforms; identifying candidate biomarkers; and undertaking multi-center validation studies. In its first 10 years, the Early Detection Research Network (EDRN) went from a ground-breaking concept to an operational success. To date, EDRN has developed more than 127 biomarkers; has launched 5 validation studies; three of which are completed, and has a number of prioritized markers ready for prevalidation and validation studies. More than 600 publications, more than 28 patents and more than 14 licenses have been generated. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial enrolled 154,934 people to evaluate the effectiveness of various screening modalities on cancer-specific mortality and created the PLCO Biorepository, an invaluable resource of data and samples that precede cancer diagnosis. Data from the screening arms of the trial have been published, providing critical data on the ability of these tests to detect cancer. Mortality data from the prostate arm was published in the NEJM in 2009. The Biorepository has been available to the entire research community since 2005, through the Etiologic and Early Markers Program (EEMS). Over 100 research projects have been approved for use of PLCO biospecimens including genome-wide association studies and environmental and life style risk association studies. The National Lung Screening Trial (NLST) was launched in 2002 and enrolled 53,456 individuals within 18 months. Participants who were current or former smokers, aged 55 to 74, were randomized to screening with either low-dose helical CT or chest x-ray. Three rounds of screening were completed by 2007 with a compliance rate of approximately 90% in both arms. Results are expected in 2011. DCP also has a robust portfolio of nutritional science research that addresses the critical need to unravel the fundamental role of food components in cancer related processes.

Risk scores and decision making: the anatomy of a decision to reduce breast cancer risk

AIM: To report the use of a risk score for risk treatment decision-making in women at risk for breast cancer in order to better understand their decision-making situation. BACKGROUND: Tamoxifen and Raloxifene are medications that have been proven to reduce the risk of breast cancer. However, women who understand their personal net benefit from Tamoxifen use chose not to take the medication. To understand this decision, the paper investigates the use of epidemiological risk information in the decision-making process for risk-reducing treatments. METHODS: The narratives of two women are analyzed as they recall their risk score and explain their decision-making process concerning participation in the Study of Tamoxifen and Raloxifene (STAR). Both in-depth interviews follow a narrative approach and were recorded in a U.S. cancer center in 2005. RESULTS: Thinking about risk by analyzing the chances of developing a disease is specific to complex decision-making situations. The associated risk-benefit analysis has to be conducted qualitatively as epidemiological risk information cannot know all details of a woman's life. In addition, a woman's decision is based on the perception of the condition as risk or as disease. Women are willing to treat risk that is perceived as disease, especially when it is based on bodily measurements on which the treatment has an effect. Women are not willing to treat a risk not perceived as disease. CONCLUSION: The net benefit of a treatment as calculated based on epidemiological data cannot easily be translated onto an individual's life. Thus, the complex experience of a woman's life at risk is highly important in decision-making situations. RELEVANCE TO CLINICAL PRACTICE: The ambiguity of statistical risk estimates should be acknowledged and the women's evaluation of her risk valued in risk treatment decision-making.

Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing Breast Cancer

The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.

Two Good Choices to Prevent Breast Cancer: Great Taste, Less Filling

An important report in this issue of the journal by Vogel et al. (beginning on p. 696) discloses long-term follow-up data of the Study of Tamoxifen and Raloxifene (STAR) showing persisting strong effects of both drugs in preventing invasive and noninvasive breast cancer after drugs were stopped in 2006. In addition, safety improved with longer follow-up (median of 81 months versus 47 months for the initial report). For 12 years, the public has avoided Food and Drug Administration-approved tamoxifen or raloxifene for breast cancer risk reduction; it is time to reemphasize the great preventive benefit of these agents to the public.