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1.
Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan''s health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of ⩾5.01% starting at younger age, whereas unfavourable results, that is ‘cost more and gain less'' or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of ⩽5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment. 相似文献
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Davide Serrano Matteo Lazzeroni Sara Gandini Debora Macis Harriet Johansson Jennifer Gjerde Ernst Lien Irene Feroce Giancarlo Pruneri Maria Teresa Sandri Fabio Bassi Fabricio Brenelli Alberto Luini Massimiliano Cazzaniga Clara Varricchio Aliana Guerrieri-Gonzaga Andrea DeCensi Bernardo Bonanni 《Breast cancer research : BCR》2013,15(3):R47
Introduction
We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model.Methods
Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers.Results
Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype.Conclusions
A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation. 相似文献3.
Summary The objective of this study was to evaluate the effects of raloxifene on normal breast tissue. A randomized, double-blind
study was carried out in 30 ovulatory, premenopausal women of 18–40 years of age, who had been diagnosed with fibroadenoma
of the breast. The patients were divided into two groups: Group A (placebo, n=16) and Group B (raloxifene 60 mg, n=14). The medication was given for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried
out on the 23rd day during which a sample of normal breast tissue was collected to evaluate the presence of the proliferating
cell marker Ki-67. Student’s t-test was used for the statistical analysis of data (p<0.05). Mean percentage of stained nuclei in groups A and B was 10.96 ± 1.27 and 1.21 ± 0.26, respectively (p<0.001). Raloxifene significantly reduced the proliferative activity of normal breast tissue in premenopausal women. 相似文献
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von Georgi R Thele F Hackethal A Münstedt K 《Breast cancer research and treatment》2006,98(2):167-172
Summary Within a multicentric, double-blind, placebo-controlled phase II trial, postmenopausal women with primary breast cancer were randomized to either 60 or 600 mg daily of raloxifene or placebo administered for 2 weeks prior to surgery. Circulating levels of sex-hormone binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEA-S), estrone (E1), estrone-sulfate (E1-S), estradiol (E2), and C-terminal telopeptide (CTX), were determined at baseline and the day before surgery in 37 women enrolled at the European Institute of Oncology in Milan. Raloxifene had a statistically significant different effect compared with placebo on SHBG (p<0.001) and E2 (p=0.03), without any dose–response relationship. Women on raloxifene (n=26) showed an increase from baseline of 10.7% (inter-quartile range: 5.9; 24.2) in SHBG and of 1.3% (inter-quartile range: −8.0; 24.5) in E2, whereas women on placebo (n=11) showed a decrease by 15.5% (inter-quartile range: 7.9; 18.1) and 17.3% (inter-quartile range: 6.5; 40.0), respectively. No significant differences were found on the other variables. A positive correlation was observed between DHEA-S and E1-S (p=0.001) or E2 (p<0.001), while SHBG correlated negatively with E1-S (p=0.024) and E2 (p=0.01), and positively with DHEA-S (p=0.016) and CTX (p=0.040). Our results provide evidence for an early endocrine effect of raloxifene which further suggests a favorable impact on breast cancer prevention. 相似文献
5.
Chemoprevention of breast cancer 总被引:5,自引:0,他引:5
Despite a recent trend toward improvement in the U.S. breast cancer mortality rate, breast cancer incidence (182,800 new cases anticipated in 2000) and mortality figures (over 40,800 anticipated deaths) remain the highest and second highest, respectively, of all cancers in U.S. women. In 1998, the selective-estrogen-receptor-modulator (SERM) tamoxifen achieved positive results in the Breast Cancer Prevention Trial (BCPT), leading to the Food and Drug Administration (FDA) approval of tamoxifen for risk reduction in women at high risk of breast cancer (the historic first FDA approval of a cancer preventive agent). This brought about a paradigm shift in new approaches for controlling breast cancer toward pharmacologic preventive regimens, called chemoprevention. This paper presents a comprehensive clinical review of breast cancer prevention study, highlighting issues of the extensive study of tamoxifen. These issues include the record of primary tamoxifen results in several breast-cancer risk-reduction settings (primary, adjuvant, and ductal carcinoma in situ [DCIS]); critical secondary BCPT risk-benefit findings (including quality of life issues) and their effects on counseling patients on use of tamoxifen for prevention; ethic minorities; optimal tamoxifen dose/duration; and potential impact on mortality and other issues involved with potential net benefit to society. Other breast-cancer chemoprevention issues reviewed here include women at high genetic risk (especially BRCA1 mutation carriers); raloxifene in breast cancer prevention; other SERMs; SERM resistance; and new agents and combinations currently in development. Very recent developments involving PPAR- ligands, COX-2 inhibitors, and RXR-ligands are discussed in the section on new drug development. 相似文献
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Background:
We conducted a population-based cohort study to assess whether tamoxifen treatment is associated with an increased incidence of diabetes.Methods:
Data obtained from the Taiwanese National Health Insurance Research Database were used for a population-based cohort study. The study cohort included 22 257 breast cancer patients diagnosed between 1 January 2000 and 31 December 2004. Among them, 15 210 cases received tamoxifen treatment and 7047 did not. Four subjects without breast cancer were frequency-matched by age and index year as the control group. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazards regression analysis.Results:
Breast cancer patients exhibited a 14% higher rate of developing diabetes (adjusted HR=1.14, 95% CI=1.08–1.20) compared with non-breast cancer controls, but the significant difference was limited to tamoxifen users. In addition, tamoxifen users exhibited a significantly increased risk of diabetes compared with non-tamoxifen users among women diagnosed with breast cancer (adjusted HR=1.31, 95% CI=1.19–1.45). Stratification by age groups indicated that both younger and older women diagnosed with breast cancer exhibited a significantly higher risk of diabetes than the normal control subjects did, and tamoxifen users consistently exhibited a significantly higher diabetes risk than non-tamoxifen users or normal control subjects did, regardless of age. Both recent and remote uses of tamoxifen were associated with an increased likelihood of diabetes.Conclusions:
The results of this population-based cohort study suggested that tamoxifen use in breast cancer patients might increase subsequent diabetes risk. The underlying mechanism remains unclear and further larger studies are mandatory to validate our findings. 相似文献9.
Okamoto Y Liu X Suzuki N Okamoto K Sekimoto M Laxmi YR Shibutani S 《International journal of cancer. Journal international du cancer》2008,122(9):2142-2147
Raloxifene (RAL) significantly reduced the incidence of breast cancer in women at high risk of developing the disease. Unlike tamoxifen (TAM), an increased incidence of endometrial cancer was not observed in women treated with RAL. However, RAL, having two hydroxyl moieties, can be conjugated rapidly through phase II metabolism and excreted, making it difficult to achieve adequate bioavailability by oral administration in humans. As a result, higher doses must be administered to obtain an efficacy equivalent to that achieved with TAM. To improve oral bioavailability and antitumor potential, RAL diphosphate was prepared as a prodrug. RAL diphosphate showed several orders of magnitude lower binding potential to both ER alpha and ER beta and weak antiproliferative potency on cultured human MCF-7 and ZR-75-1 breast cancer cells, as compared to RAL. However, RAL diphosphate has a much higher bioavailability than RAL, endowing it with higher antitumor potential than RAL against both 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats and human MCF-7 breast cancer implanted in athymic nude mice. The RAL prodrug may provide greater clinical benefit for breast cancer therapy and prevention. 相似文献
10.
Hölmich LR Mellemkjaer L Gunnarsdóttir KA Tange UB Krag C Møller S McLaughlin JK Olsen JH 《British journal of cancer》2003,88(6):832-838
Concern has been raised about the potential delay in breast cancer diagnosis in the augmented breast. We linked a cohort of 2955 women, who received cosmetic breast implants in Denmark during the period 1973-1997 with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group register. We identified 23 incident cases of invasive breast cancer diagnosed subsequent to breast implantation. We randomly selected 11 controls for each case from the Danish Breast Cancer Cooperative Group's register, and obtained detailed information on all study subjects about surgery, histopathology and stage of breast cancer at diagnosis, intended adjuvant treatment according to trial protocols and overall survival. We found that women with breast implants on average were diagnosed with breast cancer at the same stage as controls. Significantly more women with breast implants had tumour cells in the surgical margins according to the Danish Breast Cancer Cooperative Group's data. There was no significant difference in overall survival between the two groups after an average of 6.4 years of follow-up. Based on this limited number of women with breast cancer subsequent to breast augmentation, breast implants do not appear to delay the diagnosis of breast cancer, and no evidence of impaired survival after breast cancer diagnosis in augmented women was found. 相似文献
11.
Dongyu Zhang Hazel B. Nichols Melissa Troester Jianwen Cai Jeannette T. Bensen Dale P. Sandler 《International journal of cancer. Journal international du cancer》2020,147(3):876-886
Laboratory studies have observed chemopreventive effects of black and green tea on breast cancer development, but few epidemiologic studies have identified such effects. We investigated the association between tea consumption and breast cancer risk using data from 45,744 U.S. and Puerto Rican women participating in the Sister Study. Frequency and serving size of black and green tea consumption were measured at cohort enrollment. Breast cancer diagnoses were reported during follow-up and confirmed by medical record review. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We further investigated potential variation according to estrogen receptor (ER) status, menopausal status and body mass index (BMI). Overall, 81.6 and 56.0% of women drank black or green tea, respectively. A total of 2,809 breast cancer cases were identified in the cohort. The multivariable model suggested an inverse association between black (≥5 vs. 0 cups/week: HR = 0.88, 95% CI 0.78, 1.00, p-trend = 0.08) and green tea (≥5 vs. 0 cups/week: HR = 0.82, 95% CI 0.70, 0.95, p-trend < 0.01) consumption and breast cancer risk. We did not observe differences by ER characteristics, menopausal status or BMI. In conclusion, our study suggests drinking at least five cups of green or black tea per week may be associated with decreased breast cancer risk. 相似文献
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Mellemkjaer L Friis S Olsen JH Scélo G Hemminki K Tracey E Andersen A Brewster DH Pukkala E McBride ML Kliewer EV Tonita JM Kee-Seng C Pompe-Kirn V Martos C Jonasson JG Boffetta P Brennan P 《International journal of cancer. Journal international du cancer》2006,118(9):2285-2292
A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility. 相似文献
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SummaryObjectives To compare interval cancer rates, sensitivity and specificity of breast cancer screening between women with moderate or strong family history and women without a family history.Methods From 1996 to 1997, 115,460 women aged 50 to 69 screened by the Ontario Breast Screening Program, offering eligible women screening with mammography and clinical breast examination, were examined. Women were followed for up to 12 months after their screening examination. Family history definitions were based on the number of affected first degree relatives and their ages at diagnosis. Multivariate analysis was conducted to adjust for potential confounding variables.Results Interval cancer rates increased across family history groups and were greatest in women with a strong family history. The rate ratio (RR) for interval cancer rate in women with a strong family history compared to women without a family history approached significance (RR=2.28, 95% confidence interval (CI) 0.97–5.34), while for women with a moderate family history it did not (RR=1.37, 95% CI 0.62–3.04). A slightly but not significantly lower sensitivity was observed in women with a strong family history compared to women without a family history. There was little variation in specificity across family history groups.Conclusions Screening was able to detect a large proportion of invasive breast cancers in women with a family history, indicating their potential to benefit from regular breast cancer screening. However, due to increased interval cancer rates, screening with one-year intervals may be important even in an older population of women with a family history. 相似文献
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《Expert review of anticancer therapy》2013,13(3):443-452
Breast cancer remains the second leading cause of malignancy-related death in women in the USA, regardless of advances in novel therapeutic agents. High priority should be given to research aimed at the study of pharmacological and natural compounds that could potentially prevent the development of breast cancer in susceptible patients. Tamoxifen has been shown to reduce the incidence of estrogen receptor-positive invasive breast cancer in women with a high risk of developing this condition by nearly 50%, and studies in osteoporosis have revealed a similar protective effect of raloxifene in postmenopausal women. The aromatase inhibitors are superior to tamoxifen in reducing the recurrence of breast cancer in postmenopausal women; large clinical trials are currently evaluating the chemopreventive effect of these agents. The list of agents with the potential for chemoprevention in breast cancer is extensive and continues to expand. There is an immense need to develop drugs that will decrease the incidence of estrogen receptor-negative breast cancer in women at high risk of developing the disease. Herein, we review the most important chemopreventive agents in breast cancer and clinical trials that have evaluated their efficacy. 相似文献
16.
The value of high adherence to tamoxifen in women with breast cancer: a community-based cohort study
C McCowan S Wang A M Thompson B Makubate D J Petrie 《British journal of cancer》2013,109(5):1172-1180
Background:
Low adherence to adjuvant tamoxifen is associated with worse health outcomes but little is known about the cost-effectiveness of high adherence.Methods:
We conducted an economic evaluation using data for all women with incident breast cancer between 1993 and 2000 who were subsequently prescribed tamoxifen in the Tayside region of Scotland. Patient-level, lifetime Markov models evaluated the impact of high vs low adherence to tamoxifen using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records. Direct medical costs were estimated for each patient and quality-of-life weights were assigned. Recurrence information was collected by case note review and adherence calculated from prescribing records with low adherence classed below 80%.Results:
A total of 354 (28%) patients had a recorded recurrence and 504 (39%) died. Four hundred and seventy-five (38%) patients had low adherence over the treatment period, which was associated with reduced time to recurrence of 52% (P<0.001). Time to other cause mortality was also reduced by 23% (P=0.055) but this was not statistically significant. For an average patient over her lifetime, low adherence was associated with a loss of 1.43 (95% CI: 1.15–1.71) discounted life years or 1.12 (95% CI: 0.91–1.34) discounted quality-adjusted life years (QALYs) and increased discounted medical costs of £5970 (95% CI: £4644–£7372). Assuming a willingness to pay threshold of £25 000 per QALY, the expected value of changing a patient from low to high adherence is £33 897 (95% CI: £28 322–£39 652).Conclusion:
Patients with low adherence have shorter time to recurrence, increased medical costs and worse quality of life. Interventions that encourage patients to continue taking their treatment on a daily basis for the recommended 5-year period may be highly cost-effective. 相似文献17.
Kathrin Mühlemann Linda S. Cook Noel S. Weiss 《Breast cancer research and treatment》1994,30(2):201-204
Summary It has been hypothesized that hepatocellular carcinoma might be a long-term adverse effect of tamoxifen therapy. Data from nine population-based cancer registries in the United States were used to investigate time trends in the incidence of hepatocellular carcinoma in white women previously diagnosed with invasive breast cancer during 1974–1987 and followed until 1989. Of particular interest were the rates after 1977, the year tamoxifen was licensed by the FDA. Compared to rates in all white women, no increased risk of hepatocellular carcinoma was found in women most likely to have received tamoxifen - those 50 years of age or more at diagnosis of breast cancer and diagnosed after 1977. These results suggest that tamoxifen does not cause a large increase in the incidence of hepatocellular carcinoma within the first decade after use. However, smaller and/or later increases in the risk for hepatocellular carcinoma are possible and warrant continued monitoring of women treated with tamoxifen. 相似文献
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As tamoxifen stimulates ovarian steroidogenesis in premenopausal women, induces ovulation and increases the incidence of benign ovarian cysts, there has been concern that it might also increase ovarian cancer risk in women treated premenopausally. In a national case-control study in Britain, treatment histories were collected for 158 cases of ovarian cancer after breast cancer diagnosed at ages under 55 years and 464 controls who had breast cancer at these ages without subsequent ovarian cancer. Risk of ovarian cancer was not raised for women overall who had taken tamoxifen (odds ratio (OR)=0.9, 95% confidence interval (CI) 0.6-1.3) or for those treated when premenopausal (OR=1.0, 95% CI 0.6-1.6) or perimenopausal (OR=0.7, 95% CI 0.2-2.4). There was also no relation of risk to daily dose, duration or cumulative dose of tamoxifen, or time since last use. There was, however, a significantly raised risk in relation to non-hormonal chemotherapy. The results suggest that tamoxifen treatment of premenopausal or perimenopausal women does not materially affect ovarian cancer risk, but that non-hormonal chemotherapy might increase risk. 相似文献
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John H. Glick M.D. Richard H. Creech M.D. Susan Torri R.N. Christopher Holroyde M.D. Harvey Brodovsky M.D. Robert B. Catalano Pharm.D. Michael Varano Ph.D. 《Breast cancer research and treatment》1981,1(1):59-68
Summary Eighty-eight postmenopausal women with metastatic breast cancer, in whom estrogen receptors (ER) were positive or unknown, were treated on a controlled trial to determine the effectiveness of tamoxifen and to assess the therapeutic advantage of sequentially adding low-dose cyclophosphamide-methotrexate-5-fluorouracil (CMF) chemotherapy in tamoxifen responders. Patients with known ER negative status were not studied. After the initial 12-week treatment with tamoxifen alone, 60% of ER positive patients achieved complete or partial response as did 35% in whom ER were unknown. Response status further improved in 18% randomized to continue tamoxifen alone vs 31% in whom CMF was added to tamoxifen. There were no statistically significant differences in time to the development of progressive disease or survival between the ER positive and ER unknown patients or between the tamoxifen and tamoxifen plus CMF groups. We conclude that inability to determine ER status should not prejudice against the use of tamoxifen in postmenopausal patients with advanced breast cancer. No benefit has been demonstrated from the addition of CMF chemotherapy in tamoxifen responders.
Address for reprints: J.H. Glick, M.D., Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104. 相似文献