Medical Education - Research Publications
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ItemThe cost of breast cancer recurrences.(Springer Science and Business Media LLC, 1992-03)Information about the costs of recurrent breast cancer is potentially important for targeting cost containment strategies and analysing the cost-effectiveness of breast cancer control programmes. We estimated these costs by abstracting health service and consumable usage data from the medical histories of 128 patients, and valuing each of the resources used. Resource usage and costs were summarised by regarding the recurrence as a series of episodes which were categorised into five anatomical site-based groups according to the following hierarchy: visceral, central nervous system (CNS), bone, local and other. Hospital visits and investigations comprised 78% of total costs for all episodes combined, and there were significant differences between the site-based groups in the frequency of hospital visits and most investigations. Total costs were most accurately described by separate linear regression models for each group, with the natural logarithm of the cost of the episode as the dependent variable, and predictor variables including the duration of the episode, duration squared, duration cubed and a variable indicating whether the episode was fatal. Visceral and CNS episodes were associated with higher costs than the other groups and were more likely to be shorter and fatal. A fatal recurrence of duration 15.7 months (the median for our sample) was predicted to cost $10,575 (Aus + 1988; or 4,877 pounds). Reduction of the substantial costs of recurrent breast cancer is likely to be a sizable economic benefit of adjuvant systemic therapy and mammographic screening. We did not identify any major opportunities for cost containment during the management of recurrences.
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ItemQuantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer(NATURE PUBLISHING GROUP, 2004-11-29)We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.
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ItemImpact of CYP19A1 and ESR1 variants on early-onset side effects during combined endocrine therapy in the TEXT trial(BIOMED CENTRAL LTD, 2016-11-08)BACKGROUND: Single nucleotide polymorphisms (SNPs) in the estrogen receptor 1 (ESR1) and cytochrome P450 19A1 (CYP19A1) genes have been associated with breast cancer risk, endocrine therapy response and side effects, mainly in postmenopausal women with early breast cancer. This analysis aimed to assess the association of selected germline CYP19A1 and ESR1 SNPs with early-onset hot flashes, sweating and musculoskeletal symptoms in premenopausal patients enrolled in the Tamoxifen and Exemestane Trial (TEXT). METHODS: Blood was collected from consenting premenopausal women with hormone-responsive early breast cancer, randomly assigned to 5-years of tamoxifen plus ovarian suppression (OFS) or exemestane plus OFS. DNA was extracted with QIAamp kits and genotyped for two CYP19A1 (rs4646 and rs10046) and three ESR1 (rs2077647, rs2234693 and rs9340799) SNPs by a real-time pyrosequencing technique. Adverse events (AEs) were recorded at baseline and 3-monthly during the first year. Associations of the genotype variants with grade ≥2 early-onset targeted AEs of hot flashes/sweating or musculoskeletal events were assessed using logistic regression models. RESULTS: There were 2660 premenopausal patients with breast cancer in the intention-to-treat population of TEXT, and 1967 (74 %) are included in this translational study. The CYP19A1 rs10046 variant T/T, represented in 23 % of women, was associated with a reduced incidence of grade ≥2 hot flashes/sweating (univariate odds ratio (OR) = 0.78; 95 % CI 0.63-0.97; P = 0.03), more strongly in patients assigned exemestane + OFS (TT vs CT/CC: OR = 0.65, 95 % CI = 0.48-0.89) than assigned tamoxifen + OFS (OR = 0.94, 95 % CI = 0.69-1.27, interaction P = 0.03). No association with any of the CYP19A1/ESR1 genotypes and musculoskeletal AEs was found. CONCLUSION: The CYP19A1 rs10046 variant T/T favors lower incidence of hot flashes/sweating under exemestane + OFS treatment, suggesting endocrine-mediated effects. Based on findings from others, this SNP may potentially enhance treatment adherence and treatment efficacy. We plan to evaluate the clinical impact of this polymorphism during time, pending sufficient median follow up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00066703, registered August 6, 2003.