National Cancer Institute®
Last Modified: April 1, 2002
UI - 11686016
AU - Gradishar WJ; Jordan VC
TI - The evolving role of endocrine therapy for treatment and prevention of breast cancer.
SO - Cancer Chemother Biol Response Modif 2001;19():215-36
AD - Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, 676 North St. Clair Street, Suite 850, Chicago, IL 60611-2927, USA.
UI - 11759823
AU - Croce M V; Isla-Larrain M T; Capafons A; Price M R; Segal-Eiras A
TI - Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women.
SO - Breast Cancer Res Treat 2001 Sep;69(1):1-11
AD - Comision de Investigaciones Cientificas de la Provincia de Buenos Aires, Argentina.
Serum levels of MUC1 and antibodies (Abs) against MUC1 (IgG and IgM-MUC1) were evaluated in healthy women related to pregnancy and lactation status. A total of 149 serum samples were obtained from: nulliparous, primiparous pregnant, multiparous pregnant that have lactated, multiparous pregnant without lactation, multiparous non-pregnant actual lactating, multiparous non-pregnant that have lactated and finally, multiparous non-pregnant women without lactation. In all assays, we included pre- and post-serum samples belonging to a breast cancer patient vaccinated with a MUC1 derived peptide. CASA test was employed to measure MUC1 while IgG- and IgM-MUC1 serum Abs were evaluated with an ELISA using a 100 mer peptide as catcher. In all groups, mean IgM levels were higher than IgG mean values; when samples were grouped in pregnants versus non-pregnants, a significant difference was detected with both Abs, being raised in non-pregnants. When samples were grouped in lactating versus non-lactating a significant difference was detected with IgG-MUC1, being raised in lactating women while no significant difference was found with IgM-MUC1. The evaluation of serum MUC1 levels confirmed previous results since a significant difference between pregnant versus non-pregnant groups was found while lactating versus non-lactating samples did not. CONCLUSIONS: (i) Increased MUC1 serum levels are apparently associated with pregnancy but not with lactation; (ii) MUC1 Abs are mainly associated with lactation and with non-pregnant status. These results may be considered a contribution on studies about protection against breast cancer induced by pregnancy and lactation.
UI - 11759825
AU - Bonanni B; Johansson H; Gandini S; Guerrieri-Gonzaga A; Torrisi R;
TI - Sandri M T; Cazzaniga M; Mora S; Robertson C; Lien E A; Decensi A Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women.
SO - Breast Cancer Res Treat 2001 Sep;69(1):21-7
AD - Division of Chemoprevention, European Institute of Oncology, Milan, Italy.
The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
UI - 11845096
AU - Myles J; Duffy S; Nixon R; Boggis C; Howell A; Shenton A; Evans G
TI - Initial results of a study into the effectiveness of breast cancer screening in a population identified to be at high risk.
SO - Rev Epidemiol Sante Publique 2001 Oct;49(5):471-5
AD - Department of Statistics, Mathematics and Epidemiology, Imperial Cancer Research Fund, 61 Lincoln's Inns Fields, London, WC2A 3PX. firstname.lastname@example.org
BACKGROUND: Women are frequently referred to genetic clinics because of a family history of breast or ovarian cancer, conferring a moderate increased risk of the disease, but not sufficient in itself to indicate gene mutation analysis. One possible management strategy is to offer regular mammographic screening, possibly earlier in life and more frequently than in the general population. This strategy is used in many parts of the UK, although it has not been formally evaluated. METHODS: In this paper we present some early results on the effectiveness of a programme of mammography in 2,998 women aged 19-71 with a moderate family history of breast cancer in Manchester. We estimated the test and programme sensitivity and sojourn time, using different statistical methods. RESULTS: Fifty breast cancers were diagnosed. The incidence rate observed was 4.46 per thousand person-years. The incidence expected from the segregation analysis of Claus et al. was 3.75 per thousand person-years. Screen-detection rates at first and subsequent screens were 5.00 and 4.93 per thousand respectively. Interval cancer incidence in the first year following a negative screen was 0.91 per thousand person-years. Screening test sensitivity was estimated conservatively as 83%, programme sensitivity as 70%. CONCLUSIONS: Early indications are that the programme is likely to be effective. Further follow-up, analysis of tumour size, node status and malignancy grade, and subsequent mortality from breast cancer is required to confirm this.
UI - 11801870
AU - Bentrem DJ; Jordan VC
TI - Role of antiestrogens and aromatase inhibitors in breast cancer treatment.
SO - Curr Opin Obstet Gynecol 2002 Feb;14(1):5-12
AD - Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
This review explores the recent experience with, and the basis for, the use of selective estrogen receptor modulators to treat and prevent breast cancer. As new agents are unveiled, they will continue to be tested against tamoxifen. A number of new selective estrogen receptor modulators are in clinical development in an attempt to decrease the unwanted effects of tamoxifen. Raloxifene holds the promise of treating osteoporosis with the beneficial side effect of breast cancer prevention. Additionally, two different classes of hormonal agents, the aromatase inhibitors and estrogen receptor down-regulators, which have no estrogen-like properties at any site, appear to be promising new treatments for advanced breast cancer.
UI - 11854547
AU - Powles TJ
TI - Breast cancer prevention.
SO - Oncologist 2002;7(1):60-4
AD - Royal Marsden NHS Trust, and Institute of Cancer Research, London, United Kingdom. email@example.com
Epidemiological, experimental, and clinical data strongly support the possibility that breast cancer will be prevented by using anti-estrogenic interventions in healthy women. Three trials involving over 20,000 women have so far been reported using tamoxifen 20 mg/day or placebo in healthy women to chemoprevent breast cancer. The American National Surgical Adjuvant Breast and Bowel P-1 Project randomized over 13,000 women to take tamoxifen or placebo and showed a 49% reduction in the early incidence of breast cancer. This was associated with a reduction in osteoporotic fractures but increases in the risks of endometrial cancer, cataract, and thromboembolism. The Royal Marsden tamoxifen trial randomized 2,500 women, and the Italian national trial randomized 5,000 women. Interim analyses from these two trials showed no effect on the early incidence of breast cancer. These results, therefore, have not been able to clearly show an overall clinical benefit of giving tamoxifen to healthy women, nor have they shown which women are likely to benefit. Another selective anti-estrogen (SERM), raloxifene, has been used in a clinical trial to prevent osteoporotic fractures in women with low bone mineral density. Annual mammography in this trial has shown an approximate 80% reduction in the early incidence of breast cancer, and further follow-up of this trial continues. New trials in chemoprevention of breast cancer being started or being proposed use luteinizing-hormone-releasing hormone analogues, aromatase inhibitors, and other SERMs.
UI - 11845940
AU - Valdez A; Banerjee K; Ackerson L; Fernandez M
TI - A multimedia breast cancer education intervention for low-income Latinas.
SO - J Community Health 2002 Feb;27(1):33-51
AD - Valdez & Associates, Mountain View, CA 94040, USA.
This paper discusses the results from the field test of a multimedia health education intervention, designed to provide breast cancer education for low income Latinas. The purpose of the field test was to ascertain whether the intervention produced significant changes in breast cancer knowledge and attitude, and screening intentions. A total of 1,197 Latina women participated in the field study at six different sites. The majority of the participants were under 65 years of age, foreign-born with less than eight years of education and a weekly household income that fell in the lowest income quintile for 1998 (<$350.00). Participants were randomly assigned to a control or intervention condition. The control group was interviewed about their breast cancer knowledge, attitude and mammography intentions prior to exposure to the intervention, and served as the baseline group. Women in the intervention group exhibited higher knowledge scores than the pretest group (Chi sq., p < .0001). Never-screened women exhibited the largest differences in knowledge scores relative to the baseline sample. The intervention also increased the likelihood of women seeking information about a mammogram.
UI - 11899786
AU - Burnside E; Belkora J; Esserman L
TI - The impact of alternative practices on the cost and quality of mammographic screening in the United States.
SO - Clin Breast Cancer 2001 Jul;2(2):145-52
AD - Department of Radiology, University of California at San Francisco, San Francisco, CA, USA.
The decentralized structure of health care in the Unites States hinders population-based analysis of breast cancer screening. Our objectives are to model mammography in the United States as a whole, to identify the variables that most profoundly affect cost and efficacy, and to develop a strategy to improve mammography screening from a population perspective. A spreadsheet model was used to represent the variables of mammography screening in the United States. The population-based national screening program in Sweden provides a framework for comparison. The outcome measures are the aggregate cost and the number of cancers detected by mammography. We used deterministic sensitivity analysis to calculate the impact of variation in practice. Aggregate costs of screening in the United States are in the range of $3-$5 billion dollars. The percentage of women screened, cost per mammogram, cancer to biopsy ratio, recall rate, and cost of recall have the most profound effect on the quality and cost of a national screening program. Variance of these high-impact variables, based on the U.S. population, modifies the aggregate cost of screening by over $2 billion. As mammography screening in the United States increases to include all women over age 40, high-impact variables should be optimized to decrease costs and improve breast cancer detection. Our model establishes which parameters are most important.
UI - 11899380
AU - Ross PJ; Powles TJ
TI - Results and implications of the Royal Marsden and other tamoxifen chemoprevention trials.
SO - Clin Breast Cancer 2001 Apr;2(1):33-6; discussion 37-40
AD - Breast Unit, Royal Marsden Hospital, Downs Road, Sutton, Surrey, SM2 5PT, UK.
A pilot chemoprevention study from the Royal Marsden Hospital in the United Kingdom demonstrated that tamoxifen could be administered safely to healthy women. This led to the establishment of multicenter trials, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 and Italian National Cancer Institute trials. An interim analysis of the Royal Marsden Hospital trial did not detect a preventive effect. The Italian trial concurred with the Royal Marsden Hospital trial. In contrast, the larger NSABP study detected a 49% reduction in the incidence of breast cancer with tamoxifen chemoprevention. Possible reasons for the different results are examined and the implications for tamoxifen chemoprevention are discussed.
UI - 11899381
AU - Costantino JP; Vogel VG
TI - Results and implications of the Royal Marsden and other tamoxifen chemoprevention trials: an alternative view.
SO - Clin Breast Cancer 2001 Apr;2(1):41-6
AD - University of Pittsburgh, Graduate School of Public Health, 130 DeSoto Street, Room 316 Parran Hall, Pittsburgh, PA 15261, USA. firstname.lastname@example.org
At the time of the release of the findings of the Breast Cancer Prevention Trial (BCPT), early interim results from two smaller European studies were also released. These smaller studies included one from the Royal Marsden (RM) Hospital in London, England, and another from the Italian National Cancer Institute. Since then, there has been much discussion about the relevance of the interim findings from the European studies and the likely reason for the failure of these studies to find a treatment effect. In some instances, the discussion has been incomplete or inconsistent with the observations from the trial. This has caused some confusion regarding the likely differences among the three studies of breast cancer prevention with tamoxifen. Recently, investigators from the RM study have published their interpretation of the reasons for the negative findings from the European studies. The discussions of the RM investigators are reviewed and used as a basis to illustrate some misconceptions regarding key differences in trial design and implementation among the BCPT and the European trials. The investigator discussions are also used to illustrate the significance of performing an appropriate benefit/risk assessment to identify women who would likely have a net beneficial effect when using tamoxifen to reduce the risk of breast cancer occurrence. Differences in terms of the characteristics of the study populations resulting in inadequate statistical power is the most likely reason for the failure to detect treatment differences in the European trials. Possible confounding due to the use of hormone replacement therapy is another reason that must be considered. Also, benefit/risk analysis indicates that tamoxifen has substantial public health potential as an approach to reduce breast cancer incidence and the physical and mental morbidity associated with this disease. The drug cannot be used indiscriminately due to the potential side effects, but benefit/risk assessment methodology can be used to identify substantial numbers of women in whom treatment would provide a net beneficial effect.
UI - 11761347
AU - Lindberg NM; Wellisch D
TI - Anxiety and compliance among women at high risk for breast cancer.
SO - Ann Behav Med 2001 Fall;23(4):298-303
AD - Department of Psychiatry, UCLA School of Medicine, Los Angeles, CA 90024-1759, USA. email@example.com
The aim of this study was to investigate the association between symptoms of depression and general anxiety, patient's feelings of vulnerability to cancer, the anxiety experienced specifically in relation to various cancer-screeningprocedures, and compliance with these procedures among women atfamilial risk for breast cancer The data were obtained from 430 patients from the High Risk Clinic at the UCLA Revlon Breast Center who completed the State-Trait Anxiety Inventory and answered questions about their perceived vulnerability to breast cancer; the anxiety they experienced regarding undergoing pap smear tests, mammograms, and breast self-examinations (BSEs); and their compliance with these cancer-screening procedures. Correlations were used to estimate the association between feelings of anxiety and compliance. We found that women attending programs targeting those at familial risk for breast cancer suffer from significant symptoms of general anxiety. General anxiety was found to be related to anxiety regarding specific screening practices but not to women's perceived vulnerability to cancer In general, neither general nor screening-specific anxiety were found to be related to patients 'compliance with screening practices; however, significant associations were found between patient's feelings of anxiety regarding BSEs and their actual performing them. BSE appears to be the only procedure for which compliance is negatively associated with procedure-specific anxiety. We offer possible explanations for this relation and discuss the possible psychological impact that recommendations regarding BSEs may have on highly anxious at-risk women.
UI - 11845768
AU - Petersen WO; Trapp MA; Vierkant RA; Sellers TA; Kottke TE; de Groen PC;
TI - Nicometo AM; Kaur JS Outcomes of training nurses to conduct breast and cervical cancer screening of Native American women.
SO - Holist Nurs Pract 2002 Jan;16(2):58-79
AD - Department of Health Sciences Research, Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA.
Native WEB (Women Enjoying the Benefit) is a unique training program for nurses employed by the Indian Health Service (IHS), tribal clinics, and other clinics with large, underserved populations. It teaches nurses breast and cervix cancer screening techniques and trains them to administer and maintain high-quality screening programs that include patient outreach, education, and training. We review American Indian (AI)/Alaska Native (AN) women's need for screening services, identify some of the obstacles to screening, and present our evaluation of the Native WEB's impact on clinics, nurses, and patients. Findings show that Native WEB training is associated with increased screening activity at all three levels.
UI - 11919047
AU - Jones LA; Chilton JA
TI - Impact of breast cancer on African American women: priority areas for research in the next decade.
SO - Am J Public Health 2002 Apr;92(4):539-42
AD - Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Despite all the gains that have been made in the area of breast cancer research, African American women suffer disproportionately from the effects of the disease. Breast cancer is the second leading cause of cancer death among African American women, exceeded only by lung cancer. Improvements in cancer incidence, mortality, and survival rates among populations are undoubtedly the outcome of quality research. Therefore, there is a need to identify and discuss issues regarding breast cancer among African American women and to determine whether these issues should be a part of the nation's breast cancer research agenda. This commentary summarizes the results of the Summit Meeting Evaluating Research on Breast Cancer in African American Women, which was held September 8-11, 2000, in Washington, DC. Listed are priority areas and some of the questions that fueled this 2-day discussion among 130 participants, including health advocates, cancer survivors, and experts representing various areas of cancer research.
UI - 11408508
AU - Lippman ME; Krueger KA; Eckert S; Sashegyi A; Walls EL; Jamal S; Cauley
TI - JA; Cummings SR Indicators of lifetime estrogen exposure: effect on breast cancer incidence and interaction with raloxifene therapy in the multiple outcomes of raloxifene evaluation study participants.
SO - J Clin Oncol 2001 Jun 15;19(12):3111-6
AD - Osteoporosis Research Program, Women's College Hospital, Toronto, Ontario, Canada. firstname.lastname@example.org
PURPOSE: To test the hypothesis that risk factors related to lifetime estrogen exposure predict breast cancer incidence and to test if any subgroups experience enhanced benefit from raloxifene. PATIENTS AND METHODS: Postmenopausal women with osteoporosis (N = 7,705), enrolled onto the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, were randomly assigned to receive placebo, raloxifene 60 mg/d, or raloxifene 120 mg/d for 4 years. Breast cancer risk was analyzed by the following baseline characteristics indicative of estrogen exposure: previous hormone replacement therapy, prevalent vertebral fractures, family history of breast cancer, estradiol level, bone mineral density (BMD), body mass index, and age at menopause. Therapy-by-subgroup interactions were assessed using a logistic regression model. RESULTS: Overall, women with the highest one-third estradiol levels (> or = 12 pmol/L) had a 2.07-fold increased invasive breast cancer risk compared with women with lower levels. Raloxifene significantly reduced breast cancer risk in both the low- and high-estrogen subgroups for all risk factors examined (P <.05 for each comparison). The women with the highest BMD and those with a family history of breast cancer experienced a significantly greater therapy benefit with raloxifene, compared with the two thirds of patients with lower BMD or those without a family history, respectively; the subgroup-by-therapy interactions were significant (P =.005 and P =.015, respectively). CONCLUSION: The MORE trial confirms that increased lifetime estrogen exposure increases breast cancer risk. Raloxifene therapy reduces breast cancer risk in postmenopausal osteoporotic women regardless of lifetime estrogen exposure, but the reduction is greater in those with higher lifetime exposure to estrogen.
UI - 11759305
AU - Meade CD; Calvo A
TI - Developing community-academic partnerships to enhance breast health among rural and Hispanic migrant and seasonal farmworker women.
SO - Oncol Nurs Forum 2001 Nov-Dec;28(10):1577-84
AD - Interdisciplinary Oncology Program, University of South Florida, USA. email@example.com
PURPOSE/OBJECTIVES: To examine effective strategies for building community-academic partnerships for the promotion of breast cancer education and outreach among rural and Hispanic migrant and seasonal farmworker women, mostly from Mexican descent. DATA SOURCES: Published research and education articles and books, community-education models, personal experiences, and community key informant feedback. DATA SYNTHESIS: Effective community partnerships for enhanced education and outreach include a framework based on a network of partners with common goals, communication processes based on trust, and bilingual/bicultural and culturally competent staff. CONCLUSIONS: A sustainable community partnership can be achieved through systematic but flexible approaches to community planning. Involvement of community members in the development and implementation of education and screening activities helps ensure that community needs are met. Relationships based on mutual respect are key. IMPLICATIONS FOR NURSING PRACTICE: Nurses can act as catalysts through community capacity building to create community-academic partnerships to reach medically underserved populations with cancer screening, outreach, and education through the delivery of strategies that are based on common goals.
UI - 11715787
AU - Thoresen SO
TI - [Mammography screening saves life]
SO - Tidsskr Nor Laegeforen 2001 Oct 20;121(25):2995
UI - 11480666
AU - Wu AH
TI - Soy and risk of hormone-related and other cancers.
SO - Adv Exp Med Biol 2001;492():19-28
AD - University of Southern California, Department of Preventive Medicine, Los Angeles 90089, USA.
UI - 11920488
AU - Kumar NB; Cantor A; Allen K; Riccardi D; Cox CE
TI - The specific role of isoflavones on estrogen metabolism in premenopausal women.
SO - Cancer 2002 Feb 15;94(4):1166-74
AD - Department of Nutrition, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA. firstname.lastname@example.org
BACKGROUND: There is increasing evidence that dietary factors may play a role in the production, metabolism, and bioavailability of sex hormones and their impact on target tissues. The specific objective of this study was to evaluate the effectiveness of supplementing a group of premenopausal women who were free of breast carcinoma with a dietary supplement of isoflavones (40 mg per day) in producing a change in steroid hormones and menstrual cycle length. METHODS: Sixty-eight consecutively recruited, premenopausal, omnivorous women of all races and ethnicities between the ages of 25 years and 55 years were admitted to the study and randomized to an experimental group supplemented with soy (40 mg genistein per day) or to a control group that consumed a placebo for a 12-week period. Changes in their anthropometric, nutritional, and hormonal biomarkers from early follicular phase were analyzed at baseline and post-intervention. RESULTS: Serum-free estradiol and estrone levels decreased moderately in the experimental group. Serum hormone-binding globulin levels increased in 41.4% of women in the experimental group compared with 37.5% of women in the placebo group. Free estradiol decreased in 53.85% of women in the experimental group compared with 37.5% of women in the placebo group. Estrone decreased in 55.56% of women in the experimental group compared with 42.86% in the placebo group. Those women in the experimental group who were consuming soy had their mean menstrual cycle length increased by 3.52 days compared with a mean decrease of 0.06 days for women in the placebo group (P = 0.04) from baseline to the third menstrual cycle. In addition, women who were taking soy had their mean follicular phase increase by 1.46 days compared with a mean increase of 0.14 days for women who were taking the placebo (P = 0.08). CONCLUSIONS: These data suggest that increased isoflavone intake affects estrogen metabolism by altering the steroid hormone concentrations and menstrual cycle length, thereby demonstrating a potential to reduce the risk for breast carcinoma. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10320
UI - 9615508
AU - Freedman TG
TI - The Breast Cancer Prevention Trial: nurses' observations.
SO - Cancer Nurs 1998 Jun;21(3):178-86
AD - University of Pennsylvania, Philadelphia 19104-6096, USA.
The Breast Cancer Prevention Trial (BCPT), a case study of a clinical prevention trial, offered a unique opportunity to examine the multifaceted and complex role of the nurse. The primary aims of this study were (a) to identify the self-descriptions of a sample of nurses involved in the day-to-day management of the BCPT, (b) to determine the nurses' perceptions of their own role and the role of the women who joined the BCPT, (c) to understand the role of the nurse in the larger context of a clinical prevention trial, and (d) to expand the knowledge base regarding some of the social and ethical underpinnings of clinical prevention trials with healthy participants. The research design was qualitative, descriptive, and exploratory. The methods used were the telephone interview and the focus group. Fifty BCPT nurses were interviewed. This included 30 telephone interviews and 20 additional BCPT nurses who participated in four national and international focus groups. After analysis of the data using ethnographic methods, a view of the multi-faceted role of the BCPT nurse emerged. On a broader scale, the inquiry raised a number of critical ethical and social issues that are relevant to future clinical prevention trials with volunteer human participants.
UI - 11377596
AU - Narod SA; Sun P; Ghadirian P; Lynch H; Isaacs C; Garber J; Weber B;
TI - Karlan B; Fishman D; Rosen B; Tung N; Neuhausen SL Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study.
SO - Lancet 2001 May 12;357(9267):1467-70
AD - Centre for Research on Women's Health, University of Toronto, 790 Bay Street, Room 750, M5G 1N8, Ontario, Canada. email@example.com
BACKGROUND: In several case-control and prospective studies, tubal ligation has been associated with a decreased risk of invasive epithelial ovarian cancer. We aimed to assess the potential of tubal ligation in reducing the risk of ovarian cancer in women who carry predisposing mutations in the BRCA1 or BRCA2 genes. METHODS: We did a matched case-control study among women from Canada, the USA, and the UK who had undergone genetic testing and who carried a pathogenic mutation in BRCA1 or BRCA2. Cases were 232 women with a history of invasive ovarian cancer, and controls were 232 women without ovarian cancer, and who had both ovaries intact. Cases and controls were matched for year of birth, country of residence, and mutation (BRCA1 or BRCA2). The odds ratio for developing ovarian cancer was estimated for tubal ligation, adjusting for oral contraceptive use, parity, history of breast cancer, and ethnic group. FINDINGS: In an unadjusted analysis among BRCA1 carriers, significantly fewer cases than controls had ever had tubal ligation (30 of 173 [18%] vs 60 of 173 [35%], odds ratio 0.37 [95% CI 0.21-0.63]; p=0.0003). After adjustment for oral contraceptive use, parity, history of breast cancer and ethnic group, the odds ratio was 0.39 (p=0.002). Combination of tubal ligation and past use of an oral contraceptive was associated with an odds ratio of 0.28 (0.15-0.52). No protective effect of tubal ligation was seen among carriers of the BRCA2 mutation. INTERPRETATION: Tubal ligation is a feasible option to reduce the risk of ovarian cancer in women with BRCA1 mutations who have completed childbearing.
UI - 11906441
AU - Fabian CJ; Kimler BF
TI - Chemoprevention for high-risk women: tamoxifen and beyond.
SO - Breast J 2001 Sep-Oct;7(5):311-20
AD - University of Kansas Medical Center, Kansas City, Kansas 66160, USA. firstname.lastname@example.org
The demonstration by the National Surgical Adjuvant Breast Project (NSABP) that 5 years of tamoxifen therapy is associated with an approximate 50% reduction in breast cancer incidence in high-risk women was a milestone in breast cancer prevention. Because tamoxifen is associated with increased risk of side-effects such as hot flashes, menstrual abnormalities, uterine cancer, and thromboembolic phenomena, its use will not be advisable or acceptable for all high-risk women. Women over 50 years of age appear to be at highest risk for serious adverse events, such as uterine cancer and thromboembolic phenomena. Individuals in whom tamoxifen-associated breast cancer risk reduction appears to outweigh risk of serious side-effects include women with prior in situ or estrogen receptor (ER)-positive invasive cancer, atypical hyperplasia, and/or women ages 35-49 with a calculated Gail 5-year risk of > or =1.7%, hysterectomized women aged 50 and older with a 5-year Gail risk of > or =2.5%, and nonhysterectomized women aged 50 and older with a 5-year Gail risk of >5.0%. It is not yet clear whether tamoxifen can reduce breast cancer incidence in women with BRCA1 and BRCA2 mutations, although preliminary evidence favors benefit for at least those with a BRCA2 mutation. Raloxifene is a selective ER modulator with less uterine estrogen agonist activity than tamoxifen, and it is hoped that it will result in fewer uterine cancers but will be equally efficacious in reducing the risk of breast cancer. The NSABP is currently conducting a randomized study of tamoxifen versus raloxifene in high-risk postmenopausal women. Approximately one third of invasive cancers are ER negative. Tamoxifen does not reduce the incidence of ER-negative cancers, nor does it appear to be effective in preventing the appearance of one third of ER-positive cancers. Priorities in prevention research are to develop (a) biomarkers to refine short-term risk assessments based on epidemiologic models, (b) biomarkers predictive of response to specific classes of preventive agents, (c) drugs with fewer side-effects and/or effective in ER-negative or ER-positive tamoxifen-resistant precancerous disease, and (d) efficient clinical trial models to assess new agent efficacy. Breast intraepithelial neoplasia (IEN) may be sampled by minimally invasive techniques and is an attractive short-term risk biomarker. Molecular abnormalities observed in IEN may be used to select potential agents for testing/therapy, and modulation of these abnormalities may be used in phase I trials to select appropriate doses and in phase II trials to assess response. Breast density volume and certain serum markers such as insulin-like growth factor-1 are also being studied as potential risk and response biomarkers. Reversal or prevention of advanced IEN as well as modulation of other risk biomarkers in randomized phase II and phase III trials is being evaluated as a means of more efficiently evaluating prevention drugs in the future. A number of agents are being developed that target molecular abnormalities in IEN, have fewer or different side effects than tamoxifen, and may be effective in ER-negative or tamoxifen-resistant disease.
UI - 11906442
AU - Anderson BO
TI - Prophylactic surgery to reduce breast cancer risk: a brief literature review.
SO - Breast J 2001 Sep-Oct;7(5):321-30
AD - Department of Surgery, University of Washington Bio-Clinical Breast Care Program, University of Washington School of Medicine, Seattle, Washington 98195, USA. email@example.com
Prophylactic mastectomy reduces the likelihood of developing breast cancer among women at heightened risk for breast cancer, but at significant personal cost.Women at increased breast cancer risk on the basis of hormonal history, family history and/or genetic mutation carrier status may consider bilateral prophylactic mastectomy with or without reconstruction to reduce their cancer risk and/or decrease their chances of cancer mortality. Women having received mastectomy as treatment for breast cancer may request contralateral mastectomy to decrease the chances of developing a second breast primary. The potential oncologic value of these procedures must be weighed carefully on a case-by-case basis against the operation's physical and psychological morbidity. The purpose of this literature review is to provide a practice-oriented summary of recent clinical studies attempting to address the relative risks and benefits of preventive surgery for breast cancer. Data are included regarding the psychological factors surrounding patient selection and quality of life outcomes, which become the cornerstone of patient satisfaction and acceptance. Taken together, these data support the Society of Surgical Oncology position statement regarding the proper application of prophylactic surgery for breast cancer.
UI - 11921176
AU - Platner JH; Bennett LM; Millikan R; Barker MD
TI - The partnership between breast cancer advocates and scientists.
SO - Environ Mol Mutagen 2002;39(2-3):102-7
AD - National Breast Cancer Coalition, Washington, DC 20036, USA. firstname.lastname@example.org
The National Breast Cancer Coalition (NBCC) is a grassroots organization that represents breast cancer advocates and is committed to eradicating breast cancer. NBCC defines a breast cancer advocate as someone who has been personally affected by the disease (e.g., a breast cancer survivor, family member, or friend), represents a constituency, and is motivated to join the fight against the disease. One of the organization's goals is to ensure that breast cancer advocates have a seat at the table when decisions are made about breast cancer research and policy. To accomplish this goal, NBCC educates advocates so that they can participate in and make meaningful contributions to legislative, scientific, and regulatory decision-making bodies. In addition to creating educational opportunities for advocates, NBCC has spearheaded several initiatives designed to directly increase the quality and quantity of breast cancer research. NBCC has also played a major role in making funding available to breast cancer researchers. Two of NBCC's most notable programs include Project LEAD, an intensive science-training course for breast cancer advocates, and the Environmental Initiative, a collection of activities designed to improve research into the relationship between breast cancer and the environment. Breast cancer advocates trained by NBCC have partnered with the scientific community and individual scientists to improve the peer review, design, and implementation of breast cancer research. Copyright 2002 Wiley-Liss, Inc.
UI - 11921177
AU - Spears PA
TI - Breast cancer prevention through the eyes of a survivor.
SO - Environ Mol Mutagen 2002;39(2-3):108-11
AD - Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA. email@example.com
UI - 11921197
AU - Zujewski J
TI - Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention.
SO - Environ Mol Mutagen 2002;39(2-3):264-70
AD - Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. firstname.lastname@example.org
Tamoxifen has been shown to decrease the risk of invasive breast cancer by 49% and noninvasive breast cancer by 50%. Tamoxifen is also associated with a threefold increased risk of endometrial cancer. Raloxifene, a second-generation selective estrogen receptor modulator (SERM), has not been associated with endometrial cancer risk, and is currently under study in a large, multi-institutional, randomized Study of Tamoxifen and Raloxifene (STAR) for breast cancer prevention in postmenopausal women. A pilot trial of raloxifene in premenopausal women to assess the safety, tolerability, effects on bone mineral density, mammographic density, and other biological endpoints is ongoing. The retinoids have been shown to decrease mammary tumors in rodent carcinogenesis models. The Italian trial of fenretinide (4-HPR) in women with stage I breast cancer randomized women to fenretinide or no intervention. This study did not show an overall effect of decreasing the risk of contralateral breast cancer. However, a protective effect was suggested in premenopausal women. It has been suggested that this effect may be related to insulin-like growth factor 1 (IGF-1), which has been shown to be modulated by fenretinide in premenopausal but not postmenopausal women. Pilot studies of SERMs alone and in combination with retinoids or other agents provide a model for testing the safety and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation in high-risk women. These studies can provide information as to both the pathophysiology of carcinogenesis and the mechanism of action of chemopreventive agents, and help select agents and doses for testing in large randomized studies.
UI - 11236399
AU - Rockhill B
TI - The privatization of risk.
SO - Am J Public Health 2001 Mar;91(3):365-8
AD - Channing Laboratory, Harvard Medical School and Brigham and Women's Hospital, Boston, Mass., USA. email@example.com
The privatization, or individualization, of risk factor knowledge has been largely responsible for a rising tide of criticism of epidemiology. The current debate seems polarized into 2 sides, those who support and those who attack "risk factor" epidemiology. This commentary aims to reinvigorate some of Geoffrey Rose's central arguments and show that this debate may miss a key point: a risk factor is a probabilistic concept that applies to an aggregate of individuals, not to a specific individual. Risk factor knowledge compels those in public health to seek actions that shift population distributions of these factors and, to do so, to understand their social, economic, and political determinants. The author links Rose's qualitative distinction between the causes of cases and the causes of incidence to an examination of the conceptual and quantitative limits of "individual risk" estimation. The attempt to predict individuals' futures on the basis of risk factor profile is especially prominent now with breast cancer. The author suggests reasons why a policy promoting private decision making about risk, while likely ineffective from a population standpoint, is viewed as the only feasible primary prevention option against this disease.