Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.

BACKGROUND: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. METHODS: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. FINDINGS: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). INTERPRETATION: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. FUNDING: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo - a substudy for IBIS I Breast Cancer Prevention Trial.

AIMS OF THE STUDY: This prospective study was performed to investigate the effects of 5-year's use of tamoxifen in preventive setting on endometrium and gynaecological symptoms. MATERIAL AND METHODS: Altogether 96 women were treated either with tamoxifen (TAM, n=45) or placebo (PLA, n=51) for up to 5 years in a randomised, double-blind IBIS I breast cancer prevention trial, clinically followed-up for an additional year and for the occurrence of malignancies at least 9 years between 2/1995 and 7/2009 in Finland. The gynaecological follow-up with trans-vaginal ultrasound and endometrial biopsies were performed at baseline, at 2.5 and 5 years and at the 6 years follow-up visit. RESULTS: Women in the TAM group discontinued the treatment significantly more often (44% versus 22%; p=0.017) and earlier (at 15 versus 30 months; p=0.044), than those in the PLA group. In postmenopausal women the median endometrial thickness was significantly increased at five years in the TAM group (median 4.3 versus 2.0mm, p=0.011), but there was no difference between the groups at one year after the treatment. There were also statistically significantly more referrals to hospitals due to gynaecological findings in the TAM group (risk rates (RR) 3.15; 95% confidence intervals (CI) 1.12-10.10), but no differences in hysterectomy rates or other serious adverse event rates were observed. CONCLUSIONS: The discontinuation rate in the TAM group was high, and the discontinuations also occurred early. Even though there were significantly more non-serious gynaecological events during the TAM treatment, routine gynaecological follow-up cannot be recommended.

Obesity and physical inactivity are related to impaired physical health of breast cancer survivors.

AIM: The aim of the present study was to examine the impact of obesity and physical activity on the health and wellbeing of patients with breast cancer shortly after the adjuvant treatments. PATIENTS AND METHODS: A total of 537 women aged 35 to 68 years with newly-diagnosed breast cancer were enrolled into the exercise intervention study. The physical activity, physical performance (2-km walking test), cardiovascular risk factors, quality of life (EORTC-QoL-C30), co-morbidities and body-mass index (BMI) were measured after the adjuvant treatments. RESULTS: Overall, 191 (39%) patients were overweight (BMI=25-30) and 85 (17%) obese (BMI ≥ 30). Physical activity and performance (p<0.001 and p<0.001), QoL (p<0.001) and high density lipoprotein (HDL)-cholesterol decreased (p<0.001) whereas age (p=0.009), co-morbidities (p<0.001), hypertension (p=0.011), metabolic syndrome (p<0.001), low density lipoprotein (LDL)-cholesterol (p=0.0043), triglycerides (p<0.001), glucose (p<0.001) and insulin (p<0.001) increased linearly with BMI. Higher waist circumference (p=0.0011), triglyceride (p=0.020), insulin (p=0.0098), rate of metabolic syndrome (p=0.028), and lower HDL-cholesterol (p=0.012) and QoL (p<0.001) were associated with low physical activity. Physical activity and BMI were the most important determinants of physical performance (p<0.001 and p<0.001, respectively). CONCLUSION: Obesity and a sedentary lifestyle are related to poor physical performance, increased risk of cardiovascular diseases and impaired QoL, leading to a vicious circle, which impairs patients' physical health and QoL.

Effectiveness of a 12-month exercise program on physical performance and quality of life of breast cancer survivors.

AIM: The study aimed at determining whether physical exercise training improves the quality of life (QoL) and physical fitness of breast cancer survivors. PATIENTS AND METHODS: A total of 573 breast cancer survivors were randomized into an exercise or a control group, 12-months after adjuvant treatments. EORTC QLQ-C30 and BR-23 questionnaires were used for evaluation of QoL, FACIT-F for fatigue and the Finnish modified version of Beck's 13-item depression scale (RBDI) for depression. Physical fitness was assessed by a 2-km walking test, and a figure-8 running test and physical activity (PA) by metabolic equivalent (MET) hours per week (MET-h/wk). RESULTS: Figure-8 running time improved significantly among the patients of the intervention group compared with the controls (p<0.001). No significant between-group differences were observed in 2-km walking time, in PA, EORTC-QLQ-C30, BR-23, FACIT-F or BDI. However, there was a linear relationship between increased PA and improved QoL (p=0.006), irrespective of the intervention. CONCLUSION: Increase in physical activity was associated with improved QoL, but no effect of the exercise intervention was observed.

Coverage and performance of colorectal cancer screening with the faecal occult blood test in Finland.

INTRODUCTION: Mortality from colorectal cancer has been shown to decrease by repeated screening using faecal occult blood (FOB) testing in randomized screening trials. This report presents coverage and performance of organized screening among the general population in Finland. METHODS: In 2004-2007, people aged 60-69 years were randomized into biennial screening and control arms. The screening test was a guaiac-based FOB test (Hemoccult) with dietary restriction and three test cards for six consecutive samples. Test positives were referred for full colonoscopy. The programme was launched in 2004 and subsequently it expanded over regions and age-cohorts. RESULTS: In 2007, the programme covered one-third of the target population and 74,592 people had been invited for screening, of them 26,866 for the second round. Uptakes for the first and second rounds, respectively, were 62% and 68% in men and 77% and 80% in women. The proportion of test positives increased from 2.4% to 2.9% from the first to the second round and the positive predictive value for cancers decreased from 7.5% to 4.3%. CONCLUSIONS: By 2007, organized colorectal cancer screening covered one-third of the target population in Finland. Implementation of screening measured with response rate was successful and met the criteria for a public health programme, but performance in terms of positive predictive value needs monitoring.