Long-Term Follow-Up of the Intergroup Exemestane Study.

Purpose The Intergroup Exemestane Study, an investigator-led study of 4,724 postmenopausal patients with early breast cancer (clinical trial information: ISRCTN11883920), has previously demonstrated that a switch from adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane was associated with clinically relevant improvements in efficacy. Here, we report the final efficacy analyses of this cohort. Patients and Methods Patients who remained disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete a total of 5 years of adjuvant endocrine therapy. Given the large number of non-breast cancer-related deaths now reported, breast cancer-free survival (BCFS), with censorship of intercurrent deaths, was the primary survival end point of interest. Analyses focus on patients with estrogen receptor-positive or unknown tumors (n = 4,599). Results At the time of the data snapshot, median follow-up was 120 months. In the population that was estrogen receptor positive or had unknown estrogen receptor status, 1,111 BCFS events were observed with 508 (22.1%) of 2,294 patients in the exemestane group and 603 (26.2%) of 2,305 patients in the tamoxifen group. The data corresponded to an absolute difference (between exemestane and tamoxifen) at 10 years of 4.0% (95% CI, 1.2% to 6.7%), and the hazard ratio (HR) of 0.81 (95% CI, 0.72 to 0.92) favored exemestane. This difference remained in multivariable analysis that was adjusted for nodal status, prior use of hormone replacement therapy, and prior chemotherapy (HR, 0.80; 95% CI, 0.71 to 0.90; P < .001). A modest improvement in overall survival was seen with exemestane; the absolute difference (between exemestane and tamoxifen) at 10 years in the population that was estrogen receptor positive or had unknown estrogen receptor status was 2.1% (95% CI, -0.5% to 4.6%), and the HR was 0.89 (95% CI, 0.78 to 1.01; P = .08). For the intention-to-treat population, the absolute difference was 1.6% (95% CI, -0.9% to 4.1%); the HR was 0.91 (95% CI, 0.80 to 1.03, P = .15). No statistically significant difference was observed in the proportion of patients who reported a fracture event in the post-treatment period. Conclusion The Intergroup Exemestane Study and contemporaneous studies have established that a strategy of switching to an aromatase inhibitor after 2 to 3 years of tamoxifen can lead to sustained benefits in terms of reduction of disease recurrence and breast cancer mortality.

Mindfulness based stress reduction study design of a longitudinal randomized controlled complementary intervention in women with breast cancer.

BACKGROUND: The stress of a breast cancer diagnosis and its treatment can produce a variety of psychosocial sequelae including impaired immune responses. Mindfulness Based Stress Reduction (MBSR) is a structured complementary program that incorporates meditation, yoga and mind-body exercises. Despite promising empirical evidence for the efficacy of MBSR, there is a need for randomized controlled trials (RCT). There is also a need for RCTs investigating the efficacy of psychosocial interventions on mood disorder and immune response in women with breast cancer. Therefore, the overall aim is to determine the efficacy of a Mindfulness Based Stress Reduction (MBSR) intervention on well-being and immune response in women with breast cancer. METHODS AND DESIGN: In this RCT, patients diagnosed with breast cancer, will consecutively be recruited to participate. Participants will be randomized into one of three groups: MBSR Intervention I (weekly group sessions + self-instructing program), MBSR Intervention II (self-instructing program), and Controls (non-MBSR). Data will be collected before start of intervention, and 3, 6, and 12 months and thereafter yearly up to 5 years. This study may contribute to evidence-based knowledge concerning the efficacy of MBSR to support patient empowerment to regain health in breast cancer disease. DISCUSSION: The present study may contribute to evidence-based knowledge concerning the efficacy of mindfulness training to support patient empowerment to regain health in a breast cancer disease. If MBSR is effective for symptom relief and quality of life, the method will have significant clinical relevance that may generate standard of care for patients with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01591915.

Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-1.

UNLABELLED: The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. PATIENTS AND METHODS: After a first standard dosed FEC course (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/mg(2) and cyclophosphamide 600 mg/m(2)), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2-7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). RESULTS: Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III-IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. CONCLUSION: Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.

Adjuvant! Online estimation of chemotherapy effectiveness when added to ovarian function suppression plus tamoxifen for premenopausal women with estrogen-receptor-positive breast cancer.

Adjuvant! Online (Adjuvant!) is a user-friendly, web-based tool that provides estimates of adjuvant therapy outcomes for individual patients. While reliable evidence underpins estimates for most patient cohorts, there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer. International Breast Cancer Study Group (IBCSG) Trial 11-93 enrolled 174 premenopausal women with estrogen-receptor positive, node-positive breast cancer. Among these patients, 55% had one positive axillary lymph node and 97% had three or fewer positive nodes. Patients were randomized to receive ovarian function suppression plus 5 years of tamoxifen with or without anthracycline-based chemotherapy. Estimated hazard rates and corresponding 10-year relapse-free survival percentages obtained from Trial 11-93 data were compared with those predicted using Adjuvant!. The 10-year relapse-free survival percentages predicted from Adjuvant! were 64.4% (95% CI, 61.9-67.2%) for endocrine therapy alone and 74.9% (95% CI, 73.1-76.8%) for chemoendocrine therapy. By contrast, these estimates in Trial 11-93 were 76.4% (95% CI, 65.8-84.0%) for endocrine therapy alone and 74.9% (95% CI, 64.5-82.7%) for chemoendocrine therapy. The Adjuvant! estimate for the endocrine-alone control group is lower than that observed in Trial 11-93 (P = 0.03), while the estimates for the two chemoendocrine therapy groups are similar. Adjuvant! appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer, thus overestimating the added benefit, if any, from chemotherapy for this patient population.

Changes in health-related quality of life may predict recurrent breast cancer.

BACKGROUND: Patient-reported outcomes incorporated in cancer clinical trials, are increasingly hypothesized to be predictors of disease-free survival. Previous research supports health-related quality of life (HRQoL) as an independent predictor of survival in patients with advanced or metastatic breast cancer. In contrast, recent studies provide evidence that baseline HRQoL scores are not associated with increased risk of relapse or survival in women with early-stage breast cancer. One plausible assumption might be that baseline HRQoL scores are limited as predictors of a recurrence of breast cancer several years after the initial diagnosis. In this explorative study, we examined whether changes in HRQoL over time may predict breast cancer recurrence. As a supplement, we investigated whether baseline HRQoL predicted recurrence. METHODS: The study sample consisted of 141 participants in the International Breast Cancer Study Group adjuvant Trial 12-93 and Trial 14-93, from the Western region of Sweden. HRQoL was assessed, during a 5-year follow up. Poisson regression analysis was used to estimate the hazard function of recurrence depending on time since primary diagnosis and on HRQoL variables. RESULTS: According to the Poisson multivariable regression analysis changes in physical well-being (beta=0.00439, p-value=0.0470), and nausea/vomiting (beta=-0.00612, p-value=0.0136) significantly predicted recurrence. Baseline HRQoL outcomes were not predictors of recurrence. CONCLUSIONS: Changes of HRQoL during adjuvant therapy may be associated with recurrence. This explorative finding needs prospective investigation.

Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century.

The current therapeutic strategy in breast cancer is to identify a target, such as estrogen receptor (ER) status, for tailoring treatments. We investigated the patterns of recurrence with respect to ER status for patients treated in two randomized trials with 25 years' median follow-up. In the ER-negative subpopulations most breast cancer events occurred within the first 5-7 years after randomization, while in the ER-positive subpopulations breast cancer events were spread through 10 years. In the ER-positive subpopulation, 1 year endocrine treatment alone significantly prolonged disease-free survival (DFS) with no additional benefit observed by adding 1 year of chemotherapy. In the small ER-negative subpopulation chemo-endocrine therapy had a significantly better DFS than endocrine alone or no treatment. Despite small numbers of patients, "old-fashioned" treatments, and competing causes of treatment failure, the value of ER status as a target for response to adjuvant treatment is evident through prolonged follow-up.

Is adjuvant chemotherapy of benefit for postmenopausal women who receive endocrine treatment for highly endocrine-responsive, node-positive breast cancer? International Breast Cancer Study Group Trials VII and 12-93.

To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.

Is chemotherapy necessary for premenopausal women with lower-risk node-positive, endocrine responsive breast cancer? 10-year update of International Breast Cancer Study Group Trial 11-93.

INTRODUCTION: International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation (OFS) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. METHODS: IBCSG Trial 11-93 is a randomized trial comparing four cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. There were 174 patients randomized from May 1993 to November 1998. The trial was closed before the target accrual was reached due to low accrual rate. RESULTS: Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio=1.02 (0.57-1.83); P=0.94) or overall survival (hazard ratio=0.97 (0.44-2.16); P=0.94). CONCLUSION: This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population.

Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials.

PURPOSE: To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC) with regard to patient and tumor factors, local treatment, and patterns of recurrence. PATIENTS AND METHODS: Twelve thousand two hundred six breast cancer patients entered onto 15 International Breast Cancer Study Group trials between 1978 and 2002 were categorized as having ILC, IDC, or other/mixed types. RESULTS: Seven hundred sixty-seven tumors (6.2%) were classified as ILC, 8,607 (70.5%) were classified as IDC, and 2,832 (23.2%) were classified as other. The analysis is limited to the 9,374 patients categorized as either pure IDC or ILC. The median follow-up time was 13 years. Compared with IDC, ILC was associated with older age; larger, better differentiated, and estrogen receptor (ER)-positive tumors; and less vessel invasion. Mastectomy was used more frequently for ILC (P < .01). There was a significant (P < .01) early advantage in disease-free survival and overall survival for the ILC cohort followed by a significant (P < .01) late advantage for the IDC cohort after 6 and 10 years, respectively. Similar patterns were observed in cohorts defined by ER status. ILC was associated with an increased incidence of bone events but a decrease in regional and lung events (all P < .01). CONCLUSION: ILC is more than a histologic variant of breast cancer. The diagnosis of ILC carries distinct prognostic and biologic implications.

Are patients who are found deeply unconscious, without having suffered a cardiac arrest, always breathing normally?

AIM: To evaluate how often an ambulance crew reports abnormal breathing among patients who are found deeply unconscious but without having suffered a cardiac arrest. METHODS: Patients with Glasgow Coma Scale (GCS) 3 (1+1+1) and without cardiac arrest were retrospectively evaluated, via ambulance records, for signs of abnormal breathing. RESULTS: Of 45 patients who fulfilled inclusion criteria, 24 (53%) had signs of abnormal breathing, as reported by the ambulance crew. CONCLUSION: Signs of abnormal breathing among comatose patients with no cardiac arrest appear to be relatively common. This therefore increases the risk of starting cardiopulmonary resuscitation (CPR) in such patients, which is in accordance with the present CPR guidelines for the lay person. Whether this might do harm to such patients is not known.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group.

UNLABELLED: GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Characteristics of cardiac arrest and resuscitation by age group: an analysis from the Swedish Cardiac Arrest Registry.

AIM: The objective of this study was to describe patients who experienced an out-of-hospital cardiac arrest (OHCA) by age group. METHODS: All patients who suffered from an OHCA between 1990 and 2005 and are included in the Swedish Cardiac Arrest Registry (n = 40,503) were classified into the following age groups: neonates, younger than 1 year; young children, between 1 and 4 years; older children, between 5 and 12 years; adolescents, between 13 and 17 years; young adults, between 18 and 35 years; adults not retired, between 36 and 64 years; adults retired, between 65 and 79 years; and older adults, 80 years or older. RESULTS: Ventricular fibrillation was lowest in young children (3%) and highest in adults (35%). Survival to 1 month was lowest in neonates (2.6%) and highest in older children (7.8%). Children (<18 years), young adults (18-35 years), and adults (>35 years) survived to 1 month 24.5%, 21.2%, and 13.6% of cases, respectively (P = .0003 for trend) when found in a shockable rhythm. The corresponding figures for nonshockable rhythms were 3.8%, 3.2%, and 1.6%, respectively (P < .0001 for trend). CONCLUSIONS: There is a large variability in characteristics and outcome among patients in various age groups who experienced an OHCA. Among the large age groups, there was a successive decline in survival with increasing age in shockable and nonshockable rhythms.

The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer.

PURPOSE: To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT). PATIENTS AND METHODS: Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT. RESULTS: No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LRF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P = .0010); among postmenopausal patients, LRF risk was decreased by 46% (P < .0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P < .0001). CONCLUSION: Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases.

Cost-effectiveness of exemestane versus tamoxifen as adjuvant therapy for early-stage breast cancer after 2-3 years treatment with tamoxifen in Sweden.

Aromatase inhibitors are rapidly becoming the cornerstone of endocrine treatment for advanced disease and are now also used as adjuvant treatment in early-stage disease. The objective of this study was to assess the cost-effectiveness of adjuvant treatment with exemestane versus tamoxifen for early-stage breast cancer after 2-3 years treatment with tamoxifen in Sweden. The results are based on findings in the Intergroup Exemestane Study (IES). IES was a randomized controlled trial in which postmenopausal women who had received 2-3 years of tamoxifen therapy following primary treatment of early-stage breast cancer, were randomized to either continue on tamoxifen therapy or be switched to exemestane therapy. The results showed a disease-free survival hazard ratio of exemestane relative to tamoxifen in IES of 0.69. A Markov state-transition model was developed to simulate consequences after the end of the clinical trial, and to integrate the trial data with external data on mortality, costs and quality of life specific for Swedish women. The cost per QALY gained was about euro 20,000 in the base case analysis without inclusion of consequences of coronary heart disease. Inclusion of these events increased the cost-effectiveness ratio to about euro 31,000. This means that, based on our assumption, sequential exemestane treatment in early breast cancer is a cost-effective option compared with tamoxifen alone, although more long-term data on overall survival and consequences of adverse events would be valuable to increase the validity of the analysis further.

A nationwide survey of CPR training in Sweden: foreign born and unemployed are not reached by training programmes.

AIM: To determine the number of CPR trained adults in Sweden, and the willingness of the non-trained population to attend a CPR course. An additional purpose was to investigate differences related to sex, age, residential area, socio-economic classification and country of origin. METHODS: Five thousand adults in Sweden were surveyed, which yielded 3167 valid responses, a response rate of 63%. The sample was selected at random and stratified to correlate to the geographic distribution of the population. RESULTS: The mean (S.D.) age was 46 (16) years, 54% of the respondents were females and 11% were people of foreign origin. Forty-five percent had participated in some form of CPR training. Younger respondents, those living in rural areas, those born in Sweden, employees, students and military conscripts were trained more frequently in CPR. Of the respondents with no CPR training, 50% expressed a willingness to attend a course. The most common reason for not being trained in CPR was that the respondent did not know such courses existed or that they did not know where to go for training. CONCLUSION: Somewhere between 30 and 45% of the adult population of Sweden had participated in CPR training. Half of the non-trained population was willing to learn CPR but frequently did not know that such courses existed or where they were held. Elderly people, people of foreign origin, or those not included in the workforce were less likely to have participated in CPR training.

Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials.

BACKGROUND: Others have reported ocular toxicity after adjuvant chemoendocrine therapy, but this study looked at ocular toxicity in similarly treated patients from large randomized clinical trials. METHODS: Information was retrieved on incidence and timing of ocular toxicity from the International Breast Cancer Study Group (IBCSG) database of 4948 eligible patients randomized to receive tamoxifen or toremifene alone or in combination with chemotherapy (either concurrently or sequentially). Case reports of patients with ocular toxicity were evaluated to determine whether ocular toxicity occurred during chemotherapy and/or hormonal therapy. Additional information was obtained from participating institutions for patients in whom ocular toxicity occurred after chemotherapy but during administration of tamoxifen or toremifene. RESULTS: Ocular toxicity was reported in 538 of 4948 (10.9%) patients during adjuvant treatment, mainly during chemotherapy. Forty-five of 4948 (0.9%) patients had ocular toxicity during hormone therapy alone, but only 30 (0.6%) patients had ocular toxicity reported either without receiving any chemotherapy or beyond 3 months after completing chemotherapy and, thus, possibly related to tamoxifen or toremifene. In 3 cases, retinal alterations, without typical aspects of tamoxifen toxicity, were reported; 4 patients had cataract (2 bilateral), 12 impaired visual acuity, 10 ocular irritation, 1 optical neuritis, and the rest had other symptoms. CONCLUSION: Ocular toxicity during adjuvant therapy is a common side effect mainly represented by irritative symptoms due to chemotherapy. By contrast, ocular toxicity during hormonal therapy is rare and does not appear to justify a regular program of ocular examination. However, patients should be informed of this rare side effect so that they may seek prompt ophthalmic evaluation for ocular complaints.

Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93.

PURPOSE: Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between 1993 and 2002, women > or = 60 years old with clinically node-negative operable breast cancer in whom adjuvant tamoxifen was considered indicated regardless of pathologic nodal status were randomly assigned to primary surgery plus axillary clearance (Sx + Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam for 5 consecutive years. The primary end point was QL reported by the patient and by physician assessment. RESULTS: A total of 473 patients (234 to Sx + Ax, 239 to Sx) were randomly assigned. The median age was 74 years; 80% had estrogen receptor-positive disease. In both the patients' subjective assessment of their QL and the physicians' perception of the patients' QL, the largest adverse QL effects of Ax were observed from baseline to the first postoperative assessment, but the differences tended to disappear in 6 to 12 months. At a median follow-up of 6.6 years, results for Sx + Ax and Sx yielded similar DFS (6-year DFS, 67% v 66%; hazard ratio [HR] Sx + Ax/Sx, 1.06; 95% CI, 0.79 to 1.42; P = .69) and OS (6-year OS, 75% v 73%; HR Sx + Ax/Sx, 1.05; 95% CI, 0.76 to 1.46; P = .77). CONCLUSION: Avoiding axillary clearance for women > or = 60 years old who have clinically node-negative disease and receive Tam for endocrine-responsive disease yields similar efficacy with better early QL.

Prognostic value of extracapsular tumor spread for locoregional control in premenopausal patients with node-positive breast cancer treated with classical cyclophosphamide, methotrexate, and fluorouracil: long-term observations from International Breast Cancer Study Group Trial VI.

PURPOSE: We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+). PATIENTS AND METHODS: We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years. RESULTS: In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate +/- distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (+/- 2%) without ECS, versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy. CONCLUSION: Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.

Efficacy of bystander CPR: intervention by lay people and by health care professionals.

BACKGROUND: Early cardiopulmonary resuscitation (CPR) by bystanders prior to the arrival of the rescue team has been shown to be associated with increased survival after out-of-hospital cardiac arrest. The aim of this survey was to evaluate the impact on survival of no bystander CPR, lay bystander CPR and professional bystander CPR. METHODS: Patients suffering an out-of-hospital cardiac arrest in Sweden between 1990 and 2002 who were given CPR and were not witnessed by the ambulance crew were included. RESULTS: In all, 29,711 patients were included, 36% of whom received bystander CPR prior to the arrival of the rescue team. Among the latter, 72% received CPR from lay people and 28% from professionals. Survival to 1 month was 2.2% among those who received no bystander CPR, 4.9% among those who received bystander CPR from lay people (p<0.0001) and 9.2% among those who received bystander CPR from professionals (p<0.0001 compared with bystander CPR by lay people). In a multivariate analysis, lay bystander CPR was associated with improved survival compared to no bystander CPR (OR: 2.04; 95% CI: 1.72-2.42), and professional bystander CPR was associated with improved survival compared to lay bystander CPR (OR: 1.37; 95% CI: 1.12-1.67). CONCLUSION: Among patients suffering an out-of-hospital cardiac arrest, bystander CPR by lay persons (excluding health care professionals) is associated with an increased chance of survival. Furthermore, there is a distinction between lay persons and health care providers; survival is higher when the latter perform bystander CPR. However, these results may not be explained by differences in the quality of CPR.