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Individual epidemiologic studies and a meta-analysis of those studies suggest that the relative risk of invasive lobular and compared to invasive ductal cancer is particularly affected by combined hormone replacement therapy (HRT) in postmenopausal women, with an approximate doubling of risk of invasive lobular breast cancer in current users. However, this was not seen in the Women's Health Initiative trial comparing combined HRT and placebo, although this trial had only modest statistical power to demonstrate the effect. In the absence of some obvious source of bias (screening mammography rates were well balanced between HRT users and non-users in most studies), this evidence supports the hypothesis that combined HRT increases the risk of lobular breast cancer. [ABSTRACT FROM AUTHOR]

A reply is presented by Drs. Peter M. Ravdin, Kathleen A. Cronin and Rowan T. Chlebowski to letters to the editor about their article "The decrease in breast-cancer incidence in 2003 in the United States."

An initial analysis of data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries shows that the age-adjusted incidence rate of breast cancer in women in the United States fell sharply (by 6.7%) in 2003, as compared with the rate in 2002. Data from 2004 showed a leveling off relative to the 2003 rate, with little additional decrease. Regression analysis showed that the decrease began in mid-2002 and had begun to level off by mid-2003. A comparison of incidence rates in 2001 with those in 2004 (omitting the years in which the incidence was changing) showed that the decrease in annual age-adjusted incidence was 8.6% (95% confidence interval [CI], 6.8 to 10.4). The decrease was evident only in women who were 50 years of age or older and was more evident in cancers that were estrogen-receptor — positive than in those that were estrogen-receptor — negative. The decrease in breast-cancer incidence seems to be temporally related to the first report of the Women's Health Initiative and the ensuing drop in the use of hormone-replacement therapy among postmenopausal women in the United States. The contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to determine whether AJCC staging, supplemented by additional clinical and pathologic variables could identify a subpopulation of pathologically staged NSCLC patients who had been resected for cure with a low risk (<20%) of 5-year disease specific mortality. The Surveillance, Epidemiology, and End Results (SEER) registry was analyzed to identify and evaluate the disease specific 5-year mortality of 17,130 patients with resected and pathologically defined Stage I–IIIA disease initially diagnosed from 1988 to 1997. The analyses showed that American Joint Commission on Cancer (AJCC) T and N defined stage Stage I–IIIA subgroups had approximately a 30, 60, and 75% 5-year disease specific mortality, respectively. The 5366 Stage IA patients were identified as having a 5-year disease specific mortality of 25%. Further multivariate analyses of Stage IA cases showed predictors of favorable outcome to be tumor size (<10mm), histologic grade (well differentiated), and histologic subtype (bronchoalveolar cell). Subgroups identified with two or all three of these additional features had a ∼10% 5-year lung cancer specific mortality. Although nearly all patient subgroups with Stages I–IIIA resected and pathologically staged NSCLC have substantial (>20%) risk of death from their cancer within 5 years of diagnosis, for Stage IA patients additional information (tumor size, histologic grade, and histologic subtype) allows additional refinement in prognostic estimates and identification of some low risk subgroups. [Copyright &y& Elsevier]

Data from several large adjuvant breast cancer chemotherapy trials suggest that anthracycline-based chemotherapies relative to non-anthracycline-based adjuvant therapies are particularly effective in patients whose tumors overexpress Her2. Most trials show some evidence of this effect, but the interaction generally has not been confirmed statistically, perhaps because the trials are underpowered. In addition, there have been a multiplicity of Her2 immunohistochemistry techniques used in these studies, which are clearly not of equivalent utility in detecting this effect. Thus, while there is good evidence that further work in this area will be of value, at this time the results are inconclusive and not ready for clinical application. [ABSTRACT FROM AUTHOR]

Objective To identify variables within the patient-oncologist communication pattern that impact overall patient comprehension and satisfaction within the breast cancer adjuvant therapy (AT) setting. Setting and participants Fifty patients were recruited from a number of academic and community-based oncology practices. Fifteen oncologists participated. Main variables Three communication variables were identified: percentage of total utterances spoken by the patient, percentage of total physician utterances that were coded as affective (i.e. emotional), and total number of questions asked by the patient during the consultation. Knowledge and satisfaction were assessed by a variety of outcome measures, including knowledge items and satisfaction as measured by VASs, the satisfaction with decision scale and the decisional conflict scale. Results The level of patient knowledge about breast cancer and satisfaction with the clinical encounter showed a tendency to correlate with the variables measuring aspects of patient-physician communication style. Patients who spoke more or asked more questions tended to be more knowledgeable whilst patients whose physicians used more affective language tended to know less but to be more satisfied with their clinical encounter. Conclusions In order to optimize patients’ degree of comprehension and satisfaction with their breast cancer adjuvant therapy, physicians need to increase their affective participation in clinical encounters whilst encouraging patients to ask questions and to actively participate in the decision-making process. [ABSTRACT FROM AUTHOR]

Investigates the possibility of using prognostic indicators to predict axillary node status of patients with primary breast cancer. Review of related literature; Number of subjects in study; Source of data.

The article comments on a paper which reports the changes in screening mammography, menopausal hormone therapy, and breast cancer incidence in the Kaiser Permanente Northwest health plan. The authors stress that the researchers have failed to consider on what causes the decline in incidence between 2000 and 2004. A randomized trial is considered not helpful in population studies. The authors also emphasize that the paper is not done at the level of individual patient data.

Discusses the use of tamoxifen and aromatase inhibitors to treat breast cancer. Use of aromatase inhibitors to block the aromitization of precurseors to estrogen in postmenopausal women and reduce systemic estrogen levels; Reference to a study in this issue which compares the aromatase inhibitor anastrozole with tamoxifen, as well as studies the effectiveness of a combination of the agents; Possible side effects of anastrozole.

Summary: The leading parameters that define treatment recommendations in early breast cancer are oestrogen-receptor, progesterone-receptor, and human epidermal growth-factor status. Although some pathologists report Ki67 in addition to other biological markers, the existing guidelines of the American Society of Clinical Oncology do not include Ki67 in the list of required routine biological markers. The advent of new genetic tests has emphasised the role of proliferative genes, including Ki67, as prognostic and predictive markers. Additionally, randomised studies have retrospectively reviewed data and reported on the role of Ki67 in breast cancer. In light of new data, we have re-assessed evidence that could change guidelines to include Ki67 in the standard pathological assessment of early breast cancers. This review provides an update on the current knowledge on Ki67 and of the evidence in the published work about the prognostic and predictive role of this marker, and provides information on the laboratory techniques used to determine Ki67. [Copyright &y& Elsevier]

The article focuses on a parallel, randomised trial which assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy in postmenopausal women with endocrine-responsive, node-positive breast cancer. The patients used in the study were randomly assigned by a computer algorithm. An analysis by intention was also conducted to treat eligible patients. Findings revealed the effectiveness of chemotherapy with cyclophosphamide, doxorubicin and fluorouracil (CAF) plus tamoxifen given sequentially than adjuvant therapy.

PURPOSE: According to the Institute of Medicine, high-quality cancer care should include effective communication between clinicians and patients about the risks and benefits, expected response, and impact on quality of life of a recommended therapy. In the delivery of oncology care, the barriers to and facilitators of communication about potential long-term and late effects, post-treatment expectations, and transition to survivorship care have not been fully defined. PATIENTS AND METHODS: We collected qualitative data through semistructured interviews with medical oncologists and focus groups with breast cancer survivors and applied the Theoretical Domains Framework to systematically analyze and identify the factors that may influence oncologists' communication with patients with breast cancer about the long-term and late effects of adjuvant therapy. RESULTS: Eight key informant interviews with medical oncologists and two focus groups with breast cancer survivors provided data. Both oncologists and patients perceived information on long-term effects as valuable in terms of improved clinical communication but had concerns about the feasibility of inclusion before treatment. They described the current approaches to communication of therapy risks as a brief laundry list that emphasized acute adverse effects and minimized more long-term issues. We describe the barriers to communication about potential long-term effects from the perspectives of both groups. CONCLUSION: This study provides insight into oncologists' communication with patients with breast cancer regarding the potential long-term and late effects of adjuvant chemotherapy and about setting realistic expectations for life after treatment. Opportunities to improve oncologists' communication about the potential toxicities of therapy, particularly regarding long-term and late effects, should be examined further. [ABSTRACT FROM AUTHOR]

Importance Online prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about adjuvant systemic therapy. However, their validity for young breast cancer patients is debated. Objective To assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality, and second, its breast cancer–specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years. Design Hospital-based cohort. Setting General and cancer hospitals. Participants A consecutive series of 2710 patients without a prior history of cancer, diagnosed between 1990 and 2000 with unilateral stage I–III breast cancer aged <50 years. Main outcome measures Calibration and discriminatory accuracy, measured with C-statistics, of estimated 10-year all-cause and breast cancer–specific mortality. Results Overall, PREDICT's calibration for all-cause mortality was good (predicted versus observed) mean difference : −1.1% (95%CI: −3.2%–0.9%; P = 0.28). PREDICT tended to underestimate all-cause mortality in good prognosis subgroups (range mean difference : −2.9% to −4.8%), overestimated all-cause mortality in poor prognosis subgroups (range mean difference : 2.6%–9.4%) and underestimated survival in patients < 35 by −6.6%. Overall, PREDICT overestimated breast cancer–specific mortality by 3.2% (95%CI: 0.8%–5.6%; P = 0.007); and also overestimated it seemingly indiscriminately in numerous subgroups (range mean difference : 3.2%–14.1%). Calibration was poor in the cohort of patients with the lowest and those with the highest mortality probabilities. Discriminatory accuracy was moderate-to-good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the results were similar for breast cancer–specific mortality. Adjuvant!'s calibration and discriminatory accuracy for both all-cause and breast cancer–specific mortality were in line with PREDICT's findings. Conclusions Although imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings were similar. Prognostication tools should be used with caution due to the intrinsic variability of their estimates, and because the threshold to discuss adjuvant systemic treatment is low. Thus, seemingly insignificant mortality overestimations or underestimations of a few percentages can significantly impact treatment decision-making. [ABSTRACT FROM AUTHOR]

Abstract: Background: The MINDACT (Microarray In Node-negative and 1–3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included. Methods: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online. Patients with both clinical (C) and genomic (G) high risks are offered adjuvant CT; those with both C and G low risks do not receive CT; patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk. CT randomisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy randomisation between letrozole and tamoxifen→letrozole are offered. Results: During the pilot phase 46% of screened patients were enrolled. Main reasons for non-enrolment were node positivity before trial amendment, sample quality problems and failure to meet logistic settings. Among the 800 patients, 386 (48%) were C-low/G-low, 198 (24.8%) as C-high/G-high, 75 (9.4%) as C-low/G-high and 141 (17.6%) as C-high/G-low. In total 216 (27%) cases were discordant. The difference between patients with C-high (42%) and G-high risk (34%) is 8.25% (95% confidence interval (CI), 4.7–11.8%; P <.0001). Compliance with the treatment decision was high (>92%). Conclusions: The logistically complex MINDACT trial is feasible in a multinational setting. The proportion of discordant patients, the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses. [Copyright &y& Elsevier]

Background Mammographic screening has led to a proportional shift toward earlier-stage breast cancers at presentation. We assessed whether the method of detection provides prognostic information above and beyond standard prognostic factors and investigated the accuracy of predicted overall and breast cancer–specific survival by the computer tool Adjuvant! among patients with screen-detected, interval, and nonscreening-related carcinomas. Methods We studied 2592 patients with invasive breast cancer who were treated at the Netherlands Cancer Institute from January 1, 1990, through December 31, 2000. Overall and breast cancer–specific survival probabilities among patients with mammographically screen-detected (n = 958), interval (n = 417), and nonscreening-related (n = 1217) breast carcinomas were compared. Analyses were adjusted for clinicopathologic characteristics and adjuvant systemic therapy. Because of gradual implementation of population-based screening in the Netherlands, analyses were stratified a priori according to two periods of diagnosis. All statistical tests were two-sided. Results Screen detection was associated with reduced mortality (adjusted hazard ratio for all-cause mortality = 0.74, 95% confidence interval = 0.63 to 0.87, P < .001, and adjusted hazard ratio for breast cancer–specific mortality = 0.62, 95% confidence interval = 0.50 to 0.78, P < .001, respectively) compared with nonscreening-related detection. The absolute adjusted reduction in breast cancer–specific mortality was 7% at 10 years. The prognostic value of the method of detection was independent of the period of diagnosis and was similar across tumor size and lymph node status categories, indicating its prognostic value beyond stage migration. Adjuvant! underestimated breast cancer–specific survival in patients with screen-detected (−3.2%) and interval carcinomas (−5.4%). Conclusions Screen detection was found to be independently associated with better prognosis for overall and breast cancer–specific survival and to provide prognostic information beyond stage migration among patients with invasive breast cancer. We propose that the method of detection should be taken into account when estimating individual prognosis. [ABSTRACT FROM PUBLISHER]

The article offers information on a study which investigated the effects of therapy with estrogen combined with progestin on cumulative breast cancer incidence and mortality following a total mean follow-up of 11 years, through August 14, 2009. The study population of 16,608 postmenopausal women between the ages of 50 to 79 years who have not undergone hysterectomy in U.S. clinical centers were randomly assigned to receive combined conjugated equine estrogens, plus medroxyprogesterone acetate or placebo pill. Main outcome measures were invasive breast cancer incidence and breast cancer mortality. A discussion on the research findings is detailed.

Summary: Background: The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. Methods: The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. Findings: There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0·006; hazard ratio [HR] 2·64, 95% CI 1·33–5·27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score <18; log-rank p=0·97; HR 1·02, 0·54–1·93), but an improvement in disease-free survival for those with a high recurrence score (score ≥31; log-rank p=0·033; HR 0·59, 0·35–1·01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0·029), with no additional prediction beyond 5 years (p=0·58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. Interpretation: The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes. Funding: National Cancer Institute and Genomic Health. [Copyright &y& Elsevier]

Background: Despite trials of mammography and widespread use, optimal screening policy is controversial. Objective: To evaluate U.S. breast cancer screening strategies. Design: 6 models using common data elements. Data Sources: National data on age-specific incidence, competing mortality, mammography characteristics, and treatment effects. Target Population: A contemporary population cohort. Time Horizon: Lifetime. Perspective: Societal. Interventions: 20 screening strategies with varying initiation and cessation ages applied annually or biennially. Outcome Measures: Number of mammograms, reduction in deaths from breast cancer or life-years gained (vs. no screening), false-positive results, unnecessary biopsies, and overdiagnosis. Results of Base-Case Analysis: The 6 models produced consistent rankings of screening strategies. Screening biennially maintained an average of 81% (range across strategies and models, 67% to 99%) of the benefit of annual screening with almost half the number of false-positive results. Screening biennially from ages 50 to 69 years achieved a median 16.5% (range, 15% to 23%) reduction in breast cancer deaths versus no screening. Initiating biennial screening at age 40 years (vs. 50 years) reduced mortality by an additional 3% (range, 1% to 6%), consumed more resources, and yielded more false-positive results. Biennial screening after age 69 years yielded some additional mortality reduction in all models, but overdiagnosis increased most substantially at older ages. Results of Sensitivity Analysis: Varying test sensitivity or treatment patterns did not change conclusions. Limitation: Results do not include morbidity from false-positive results, patient knowledge of earlier diagnosis, or unnecessary treatment. Conclusion: Biennial screening achieves most of the benefit of annual screening with less harm. Decisions about the best strategy depend on program and individual objectives and the weight placed on benefits, harms, and resource considerations. Primary Funding Source: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Summary: Background: Adjuvant! is a web-based program that calculates individualised 10-year survival probabilities and predicted benefit of adjuvant systemic therapy. The Adjuvant! model has not been validated in any large European series. The aim of our study was to validate Adjuvant! in Dutch patients, investigating both its calibration and discriminatory accuracy. Methods: Patients who were at least partly treated at the Netherlands Cancer Institute for breast cancer between 1987 and 1998 were included if they met the following criteria: tumour size T1 (≤2 cm), T2 (2–5 cm), or T3 (>5 cm), invasive breast carcinoma, with information about involvement of axillary lymph nodes available, no distant metastases, primary surgery, axillary staging, and radiotherapy according to national guidelines. Clinicopathological characteristics and adjuvant treatment data were retrieved from hospital records and medical registries and were entered into the Adjuvant! (version 8.0) batch processor with blinding to outcome. Endpoints were overall survival and the proportion of patients that did not die from breast cancer (breast-cancer-specific survival [BCSS]). Findings: 5380 patients were included with median follow-up of 11·7 years (range 0·03–21·8). The 10-year observed overall survival (69·0%) and BCSS (78·6%) and Adjuvant! predicted overall survival (69·1%) and BCSS (77·8%) were not statistically different (p=0·87 and p=0·18, respectively). Moreover, differences between predicted and observed outcomes were within 2% for most relevant clinicopathological subgroups. In patients younger than 40 years, Adjuvant! overestimated overall survival by 4·2% (p=0·04) and BCSS by 4·7% (p=0·01). The concordance index, which indicates discriminatory accuracy at the individual level, was 0·71 for BCSS in the entire cohort. Interpretation: Adjuvant! accurately predicted 10-year outcomes in this large-scale Dutch validation study and is of use for adjuvant treatment decision making, although the results may be less reliable in some subgroups. Funding: Dutch National Genomics Initiative-Cancer Genomics Center, Dutch Cancer Society-KWF. [Copyright &y& Elsevier]

Background: The objectives of this study were to examine the patterns of use for adjuvant therapy and the changes in surgical practice for patients with early stage breast cancer and to describe how recent large clinical trial results impacted the patterns of care at The University of Texas M. D. Anderson Cancer Center (MDACC).Methods: The study included 5486 women who were diagnosed with stage I through IIIA breast cancer between 1997 and 2004 and received their treatment at MDACC. A chi-square trend test and multivariate logistic regression model were used to assess changes in treatment patterns over time.Results: Among lymph node-positive patients, the use of anthracycline plus taxane chemotherapy increased from 17% in 1997 to 81% in 2004 (P < .001). Meanwhile, the use of anthracyclines without taxanes dropped from 76% to 20% (P < .001) between 1997 and 2000. For postmenopausal patients who received endocrine therapy, the use of tamoxifen was replaced increasingly by the use of aromatase inhibitors (from 100% on tamoxifen in 1997 to 14% in 2004; P < .001). The percentage of women who underwent initial sentinel lymph node biopsy increased significantly during the period from 1997 to 2004 (from 1.8% to 69.7%, respectively, among patients who underwent mastectomy; and from 18.1% to 87.1%, respectively, among patients who underwent breast-conserving surgery; P < .001).Conclusions: The results from this study suggested that key findings from adjuvant therapy and surgical procedures from large clinical trials often prompt immediate changes in the patient care practices of research hospitals like MDACC. [ABSTRACT FROM AUTHOR]

Background: Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial. Methods: We analyzed the results of the WHI randomized clinical trial — in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo — and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use. Results: In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged. Conclusions: The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography. N Engl J Med 2009;360:573-87. [ABSTRACT FROM AUTHOR]

Background: Decision aids are tools that help patients make specific and deliberative choices among options. This study was a group randomized controlled trial of a novel decision aid to help patients with breast cancer make adjuvant therapy (AT) decisions. Methods: Fourteen oncology practices (n=58 physicians) were randomized to receive the decision aid or a control pamphlet. Complete data were obtained from 405 patient–oncologist pairs. Eligible patients had stage I–III disease and had completed their primary treatment. The decision aid is a simple to use computer program, titled Adjuvant!, that provides estimates of outcome with and without AT. Graphical representations of outcome are shared with patients. Consultations were audiotaped, patients interviewed, and physicians completed a self-administered survey. Results: In a multivariable model, the 54 patients (13.3%) who took no AT were more likely to have received the decision aid (p=0.02). A differential effect of the Adjuvant! Decision Guide was noted between node negative and positive patients. It was stated by 86.2% of patients that the decision aid was influential when making their treatment decision. Over 95% of patients reported that the Adjuvant Decision Guide was easy to understand and 75% of physicians believed that it helped them understand their patient's treatment preferences and 81.4% reported the information as useful for themselves. Conclusions: This study showed that a decision aid made a difference in the choice of whether or not to take AT. The decision aid allowed patients and physicians to consider the benefits of AT in an easy to understand format. Treatment decisions were more individualized for patients in the intervention than in the control group. The use of the decision aid was acceptable to both patients and physicians. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]