A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer.
ABSTRACT Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high-sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation.
Article: Recruitment of breast cancer survivors into a 12-month supervised exercise intervention is feasible.[show abstract] [hide abstract]
ABSTRACT: The BREX study is one of the largest randomised prospective exercise interventions of breast cancer survivors which aims at investigate whether regular exercise could reduce the long-term side effects of the adjuvant treatments and improve quality of life. The study was limited to consider patients aged 35-68 years, who had recently completed adjuvant chemotherapy or started endocrine therapy. In this paper, we describe the recruitment process of the 413 randomised patients from the Helsinki University Hospital between September 2005 and September 2007. 768 potentially eligible patients out of the 1321 screened (via medical records) were contacted by phone. After the phone call 240 patients were excluded due to health problems that contraindicated exercise training. The most common health problems were musculoskeletal disorders. A total of 528 patients were considered as eligible for the intervention. Ultimately 413 of them agreed to participate resulting in a 53.8% recruitment rate of the potentially eligible patients. The most important reasons for declining were social, not health related. Eligible patients who did not want to participate did not differ significantly from those who participated according to age, health status, breast cancer treatment and tumour type. The high recruitment rate demonstrates breast cancer patient's willingness to participate even in long-lasting supervised exercise programs shortly after adjuvant treatments. After taking into account the selection of the population by age and musculoskeletal health, the results of the present intervention can be generalized to represent urban breast cancer patient population in Finland.Contemporary clinical trials 05/2009; 30(5):457-63. · 1.51 Impact Factor
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ABSTRACT: Kinins are highly potent vasoactive peptides. They reduce blood pressure by vasodilation and are cardio- and vasoprotective. ACE inhibitors potentiate the actions of endogenous kinins by about 50-fold. Kinins are involved in the blood pressure-lowering effects of ACE inhibitors in all forms of hypertension associated with stimulation of the renin-angiotensin system. In addition, kinins play an important role in the metabolic, and cardio- and vasoprotective effects of ACE inhibitors.Drugs 02/1997; 54 Suppl 5:23-30. · 4.23 Impact Factor
Article: Correlation between tamoxifen elimination and biomarker recovery in a primary prevention trial.[show abstract] [hide abstract]
ABSTRACT: We have shown previously that a reduction from the conventional dose of tamoxifen is associated with a comparable modulation of circulating biomarkers, including insulin-like growth factor-I and cholesterol. In the present study, we have correlated serum tamoxifen elimination with biomarker recovery in healthy subjects completing a 5-year intervention period. Tamoxifen, N-desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and 6 weeks after completion of treatment in 23 healthy postmenopausal women allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (+/-SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively, 141 +/- 50 and 226 +/- 77 ng/ml at baseline, 36 +/- 19 and 99 +/- 46 at 2 weeks, 20 +/- 15 and 61 +/- 37 at 4 weeks, and 12 +/- 9 and 36 +/- 26 at 6 weeks. Serum tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively. Body mass index was associated positively with drug's serum half-life. Compared with baseline values, the percentage increase in total cholesterol, low-density lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment completion was 5, 9, and 14%, respectively. No change during the 6-week period was observed in the placebo arm. Our findings indicate that the biomarker recovery is slower than serum tamoxifen elimination, suggesting that low tamoxifen concentrations may still exert a biological effect. In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined.Cancer Epidemiology Biomarkers & Prevention 10/2001; 10(9):967-70. · 4.12 Impact Factor