A collaboration between service users and professionals for the development and evaluation of a new program for cardiovascular risk management in persons with a diagnosis of severe mental illness: French multicenter qualitative and feasibility studies.

BACKGROUND: Persons with a diagnosis of severe mental illness have a life expectancy that is 20 years lower than the general population, and they are disproportionately affected by cardiovascular disorders. Improving the management of cardiovascular risk is one of the main challenges for the public health system. In the care pathway of persons with a diagnosis of severe mental illness, a better understanding of limiting and facilitating factors is required. The objective was to include persons with a diagnosis of severe mental illness, carers, and primary and mental health professionals in the creation and evaluation (feasibility) of a health promotion program designed to improve cardiovascular risk management through empowerment. METHODS: This study combines a mixed methodology with qualitative and quantitative components. A multicenter prospective qualitative study was conducted in seven mental health units in France and was coordinated by a steering committee composed of persons with a diagnosis of severe mental illness, carers, and primary and mental health professionals. RESULTS: This health promotion program must enable persons with a diagnosis of severe mental illness to assert their right to self-determination and to exercise greater control over their lives, beyond their diagnosis and care. Following a preliminary feasibility study, the effectiveness of this new tool will be evaluated using a randomized controlled trial in a second study. CONCLUSIONS: The findings can be used by health organizations as a starting point for developing new and improved services for persons with a diagnosis of severe mental illness.Trial registration Clinical Trials Gov NCT03689296. Date registered September 28, 2018.

Surveying End-of-Life Medical Decisions in France: Evaluation of an Innovative Mixed-Mode Data Collection Strategy.

BACKGROUND: Monitoring medical decisions at the end of life has become an important issue in many societies. Built on previous European experiences, the survey and project Fin de Vie en France ("End of Life in France," or EOLF) was conducted in 2010 to provide an overview of medical end-of-life decisions in France. OBJECTIVE: To describe the methodology of EOLF and evaluate the effects of design innovations on data quality. METHODS: EOLF used a mixed-mode data collection strategy (paper and Internet) along with follow-up campaigns that employed various contact modes (paper and telephone), all of which were gathered from various institutions (research team, hospital, and medical authorities at the regional level). A telephone nonresponse survey was also used. Through descriptive statistics and multivariate logistic regressions, these innovations were assessed in terms of their effects on the response rate, quality of the sample, and differences between Web-based and paper questionnaires. RESULTS: The participation rate was 40.0% (n=5217). The respondent sample was very close to the sampling frame. The Web-based questionnaires represented only 26.8% of the questionnaires, and the Web-based secured procedure led to limitations in data management. The follow-up campaigns had a strong effect on participation, especially for paper questionnaires. With higher participation rates (63.21% and 63.74%), the telephone follow-up and nonresponse surveys showed that only a very low proportion of physicians refused to participate because of the topic or the absence of financial incentive. A multivariate analysis showed that physicians who answered on the Internet reported less medication to hasten death, and that they more often took no medical decisions in the end-of-life process. CONCLUSIONS: Varying contact modes is a useful strategy. Using a mixed-mode design is interesting, but selection and measurement effects must be studied further in this sensitive field.

Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences.

The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence.

A longitudinal analysis of patient satisfaction with care and quality of life in ambulatory oncology based on the OUT-PATSAT35 questionnaire.

BACKGROUND: In the oncology setting, there has been increasing interest in evaluating treatment outcomes in terms of quality of life and patient satisfaction. The aim of our study was to investigate the determinants of patient satisfaction, especially the relationship between quality of life and satisfaction with care and their changes over time, in curative treatment of cancer outpatients. METHODS: Patients undergoing ambulatory chemotherapy or radiotherapy in two centers in France were invited to complete the OUT-PATSAT35, at the beginning of treatment, at the end of treatment, and three months after treatment. This questionnaire evaluates patients' perception of doctors and nurses, as well as other aspects of care organization and services. Additionally, for each patient, socio-demographic and clinical characteristics, and self-reported quality of life data (EORTC QLQ-C30) were collected. RESULTS: Of the 691 patients initially included, 561 answered the assessment at all three time points. By cross-sectional analysis, at the end of the treatment, patients who experienced a deterioration of their global health reported less satisfaction on most scales (p ≤ 0.001). Three months after treatment, the same patients had lower satisfaction scores only in the evaluation of doctors (p ≤ 0.002). Furthermore, longitudinal analysis showed a significant relationship between a deterioration in global health and a decrease in satisfaction with their doctor and, conversely, between an improvement in global health and an increase in satisfaction on the overall satisfaction scale. Global health at baseline was largely and significantly associated with all satisfaction scores measured at the following assessment time points (p < 0.0001). Younger age (<55 years), radiotherapy (versus chemotherapy) and head and neck cancer (versus other localizations) were clinical factors significantly associated with less satisfaction on most scales evaluating doctors. CONCLUSIONS: Pre-treatment self-evaluated global health was found to be the major determinant of patient satisfaction with care. The subsequent deterioration of global health, during and after treatment, emphasized the decrease in satisfaction scores, mainly in the evaluation of doctors. Early initiatives aimed at improving the delivery of care in patients with poor health status should lead to improved perception of the quality of care received.

[The places of death of people aged 80 and over in France]. / Les lieux de la fin de vie des personnes de 80 ans et plus en France.

While the places and causes of death are the subject of abundant literature, the circumstances surrounding the end of life, the ultimate phase of existence, remain largely not explored in France. The pathways through different living places taken by people aged 80 and over during the last month of existence and the factors associated with them are described thanks to the unique information and data collected by the "End of Life in France" survey.

End-of-life medical decisions in France: a death certificate follow-up survey 5 years after the 2005 act of parliament on patients' rights and end of life.

BACKGROUND: The "Patients' Rights and End of Life Care" Act came into force in France in 2005. It allows withholding/withdrawal of life-support treatment, and intensified use of medications that may hasten death through a double effect, as long as hastening death is not the purpose of the decision. It also specifies the requirements of the decision-making process. This study assesses the situation by examining the frequency of end-of-life decisions by patients' and physicians' characteristics, and describes the decision-making processes. METHODS: We conducted a nationwide retrospective study of a random sample of adult patients who died in December 2009. Questionnaires were mailed to the physicians who certified/attended these deaths. Cases were weighted to adjust for response rate bias. Bivariate analyses and logistic regressions were performed for each decision. RESULTS: Of all deaths, 16.9% were sudden deaths with no information about end of life, 12.2% followed a decision to do everything possible to prolong life, and 47.7% followed at least one medical decision that may certainly or probably hasten death: withholding (14.6%) or withdrawal (4.2%) of treatments, intensified use of opioids and/or benzodiazepines (28.1%), use of medications to deliberately hasten death (i.e. not legally authorized) (0.8%), at the patient's request (0.2%) or not (0.6%). All other variables held constant, cause of death, patient's age, doctor's age and specialty, and place of death, influenced the frequencies of decisions. When a decision was made, 20% of the persons concerned were considered to be competent. The decision was discussed with the patient if competent in 40% (everything done) to 86% (intensification of alleviation of symptoms) of cases. Legal requirements regarding decision-making for incompetent patients were frequently not complied with. CONCLUSIONS: This study shows that end-of-life medical decisions are common in France. Most are in compliance with the 2005 law (similar to some other European countries). Nonetheless, the study revealed cases where not all legal obligations were met or where the decision was totally illegal. There is still a lot to be done through medical education and population awareness-raising to ensure that the decision-making process is compatible with current legislation, the physician's duty of care and the patient's rights.

[Safety and efficacy of bevacizumab combined with taxanes in the first-line treatment of metastatic breast cancer: ATHENA study-France]. / Tolérance et efficacité du bévacizumab en association aux taxanes en première ligne dans le cancer du sein métastatique : étude ATHENA-France.

The efficacy of the combination bevacizumab-chemotherapy in the first-line treatment of metastatic breast cancer (mBC) was demonstrated in several randomized clinical trials. However, limited safety data is available in daily medical practice. ATHENA is an international phase-IIIb study conducted in 2,251 patients with locally advanced or mBC, treated in first-line with bevacizumab combined with taxanes-based chemotherapy. The primary objective is safety assessment. In France, 365 patients were included. Their median age was 56 years (24-93 years) and ECOG performance status was 0 or 1 in 93.9% of patients. Bevacizumab was essentially combined with a taxanes monotherapy: docetaxel (37.3%) or paclitaxel (28.8%) or taxanes-based combination therapy (9.4%). The most frequent grade superior or equal to 3 adverse event (AE) was neutropenia (34.5%). Grade superior or equal to 3 AEs of special interest related to bevacizumab were arterial and venous thromboembolism (5.1%), high blood pressure (4.2%), proteinuria (2.3%) and hemorrhage (2%). Median time to progression was 9.5 months (95% CI: 8.8-10.4). The safety profile and the efficacy of the combination bevacizumab-taxanes in a population more representative of daily oncology practice in France are comparable to those reported in clinical trials in mBC.

Determinants of patient satisfaction in ambulatory oncology: a cross sectional study based on the OUT-PATSAT35 questionnaire.

BACKGROUND: The aim of this study was to identify factors associated with satisfaction with care in cancer patients undergoing ambulatory treatment. We investigated associations between patients' baseline clinical and socio-demographic characteristics, as well as self-reported quality of life, and satisfaction with care. METHODS: Patients undergoing ambulatory chemotherapy or radiotherapy in 2 centres in France were invited, at the beginning of their treatment, to complete the OUT-PATSAT35, a 35 item and 13 scale questionnaire evaluating perception of doctors, nurses and aspects of care organisation. Additionally, for each patient, socio-demographic variables, clinical characteristics and self-reported quality of life using the EORTC QLQ-C30 questionnaire were recorded. RESULTS: Among 692 patients included between January 2005 and December 2006, only 6 were non-responders. By multivariate analysis, poor perceived global health strongly predicted dissatisfaction with care (p < 0.0001). Patients treated by radiotherapy (vs patients treated by chemotherapy) reported lower levels of satisfaction with doctors' technical and interpersonal skills, information provided by caregivers, and waiting times. Patients with primary head and neck cancer (vs other localisations), and those living alone were less satisfied with information provided by doctors, and younger patients (< 55 years) were less satisfied with doctors' availability. CONCLUSIONS: A number of clinical of socio-demographic factors were significantly associated with different scales of the satisfaction questionnaire. However, the main determinant was the patient's global health status, underlining the importance of measuring and adjusting for self-perceived health status when evaluating satisfaction. Further analyses are currently ongoing to determine the responsiveness of the OUT-PATSAT35 questionnaire to changes over time.

FACE: the barefaced facts of AI potency.

The use of third-generation aromatase inhibitors (AIs), such as anastrozole and letrozole, as initial adjuvant hormonal therapy in postmenopausal women (PMW) with hormone receptor-positive (HR+) breast cancer offers a significant benefit over tamoxifen for reducing recurrence risk. Clinical studies, including the Arimidex Tamoxifen Alone or in Combination (ATAC) and the Breast International Group (BIG) 1-98 trials, have proven that both anastrozole and letrozole are, respectively, superior to tamoxifen in improving disease-free survival. Although differing in design, objectives, and follow-up time, these trials offer some insight into the comparative clinical efficacy of these two nonsteroidal AIs. In particular, results from BIG 1-98 show that letrozole significantly reduces early distant metastatic (DM) events, which constitute the majority of early recurrence events. Subsequently, there is a beneficial overall survival effect emerging in the trial, whereas survival is unchanged with anastrozole after 100 months of follow-up in ATAC. Significant differences in the potency of these two drugs, vis-à-vis their degree of aromatase inhibition, have been observed in comparative trials and show that letrozole causes a more complete suppression of estrogen levels than does anastrozole. Whether this difference in potency is relevant to reductions in DM events during adjuvant therapy remains unclear. The Femara Anastrozole Clinical Evaluation trial is addressing this issue in a more unequivocal manner by comparing initial adjuvant treatment with anastrozole or letrozole in a population of breast cancer patients at high risk of recurrence: PMW with HR+ disease and axillary lymph node involvement.

Long-term efficacy and safety of letrozole for the adjuvant treatment of early breast cancer in postmenopausal women: a review.

Aromatase inhibitors (AIs) are becoming more widely used than tamoxifen as adjuvant hormonal therapy for postmenopausal women (PMW) with early breast cancer (EBC). It is clear that these drugs offer important efficacy benefits over tamoxifen and differ from tamoxifen in their safety profile. The accepted strategies for adjuvant AI therapy include initial adjuvant treatment following surgery, switching and/or sequencing from prior tamoxifen, and extended adjuvant therapy following the full 5 years of tamoxifen treatment. Among the available AIs, letrozole has been evaluated in large, well-controlled, double-blind clinical trials in the initial adjuvant, extended adjuvant, and more recently, the sequential adjuvant settings. Letrozole is the most potent of the AIs and provides near complete suppression of plasma estrogens in PMW. Letrozole also significantly reduces the occurrence of early distant metastases, the most lethal type of recurrence event, which can lead to improved survival. Clinical comparisons of letrozole with both tamoxifen and placebo have also provided important long-term safety data on the use of AIs as adjuvant therapy in PMW with EBC. The weight of clinical evidence indicates that letrozole is a safe and effective option for adjuvant hormonal therapy across all three AI treatment settings.

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results.

BACKGROUND: Letrozole is safe and effective in postmenopausal women with estrogen receptor-positive early breast cancer, but long-term aromatase inhibitor use may cause bone loss and increase fracture risk. This study evaluated an immediate or delayed strategy of bone protection therapy with zoledronic acid. METHODS: A total of 1065 patients who were receiving adjuvant letrozole were randomized to immediate-start or delayed-start zoledronic acid (4 mg intravenously biannually for 5 years). The delayed group received zoledronic acid if lumbar spine or total hip T-score decreased below -2.0 or when a nontraumatic fracture occurred. The primary endpoint was change in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints included changes in total hip BMD, serum bone turnover markers, and safety at Month 12. RESULTS: Lumbar spine BMD increased from baseline in the immediate arm, while it decreased from baseline in delayed-arm patients. At Month 12, the differences between the groups in lumbar spine and total hip BMD were 5.7% (P < .0001; 95% confidence intervals [CI], 5.2% to 6.1%), and 3.6% (P < .0001; 95% CI, 3.3 to 4.0%), respectively. Both regimens were well tolerated with few serious adverse events. Bone pain was higher in the immediate group, as expected, because some patients experienced acute-phase reactions after zoledronic acid infusion. CONCLUSIONS: At 12 months, immediate zoledronic acid therapy prevented bone loss in postmenopausal women who were receiving adjuvant letrozole.

Rurality and survival differences in lung cancer: a large population-based multivariate analysis.

Several studies have suggested rural health disadvantages. In France, studies on rural-urban patterns of lung cancer survival have yielded conflicting results. The aim of this analysis was to determine whether rural residence was associated with poor survival in three French counties. The database consisted of all primary lung cancer cases diagnosed in 2000 and 2001 collected through the Doubs cancer registry. A degree of rurality, obtained from socio-demographic and farming parameters of the 1999 French census treated with factor analysis, was attributed to each patient according to his/her place of residence. Among the 802 patients, 21% resided in rural areas, 11% were semi-urban inhabitants and 68% were urban residents. Survival differed significantly between these three rurality categories (p=0.04), with 2-year survival rates of 18, 29 and 24%, respectively. Using a Cox model, rural areas were significantly correlated with poor survival as compared with semi-urban areas (OR=1.42; 95% confidence interval=1.06-1.90; p=0.02). There was no survival difference between semi-urban and urban patients (OR=1.18; 95% confidence interval=0.91-1.53; p=0.21). Patient and tumour characteristics, especially stage and staging procedures, as well as first line treatment, did not vary with the degree of rurality. In conclusion, rurality has to be considered as a strong prognostic factor. Several intricate factors might be hypothesized such as increasing time to diagnosis leading to heavier tumour burden, worse treatment compliance and socioeconomic status. Before practical interventions can be proposed, prospective studies are warranted with further definition of rural risk factors for decreased survival in rural lung cancer patients.

Comparison of docetaxel- and vinca alkaloid-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer: a meta-analysis of seven randomized clinical trials.

INTRODUCTION: To compare the impact on overall survival (OS) of docetaxel-based chemotherapy versus vinca alkaloid-based regimens for first-line therapy of advanced non-small cell lung cancer. METHODS: A meta-analysis of all randomized, controlled trials comparing docetaxel- and vinca alkaloid-based chemotherapy was undertaken using MEDLINE, CANCERLIT, MEDSCAPE, Google Scholar, the Cochrane Library, the National Institutes of Health randomized, controlled trials register, and conference proceedings, supplemented by information from clinical study reports. All published and unpublished randomized, controlled trials (in any language) were included. Analysis was based on pooling individual logarithms of the hazard ratio for OS and the odds ratio (OR) for safety. RESULTS: From eight potentially eligible trials, seven were selected (n = 2867). Docetaxel was administered with a platinum agent (three trials), with gemcitabine (two trials), or as monotherapy (two trials). Vinca alkaloid (vinorelbine [six trials] and vindesine [one trial]) was administered with cisplatin (six trials) or alone (one trial). The pooled estimate for OS showed an 11% improvement in favor of docetaxel (hazard ratio = 0.89; 95% confidence interval: 0.82-0.96; p = 0.004). Sensitivity analyses considering only vinorelbine as a comparator or only the doublet regimens showed similar improvements. Grade 3/4 neutropenia and grade 3/4 serious adverse events were less frequent with docetaxel- versus vinca alkaloid-based regimens (OR = 0.59; 95% confidence interval: 0.38-0.89; p = 0.013 and OR = 0.68; 95% confidence interval: 0.55-0.84; p < 0.001, respectively). CONCLUSION: According to this meta-analysis, docetaxel is superior to vinca alkaloid-based regimens in terms of OS and safety for first-line therapy of advanced non-small cell lung cancer.

Assessment of care by breast cancer patients participating or not participating in a randomized controlled trial: a report with the Patients' Committee for Clinical Trials of the Ligue Nationale Contre le Cancer.

PURPOSE: Cancer patients participating in randomized controlled trials (RCTs) have not been found to have better clinical outcomes than other patients. Our objective was to assess the impact of RCTs on patients' satisfaction with care. PATIENTS AND METHODS: A prospective study was carried out in a cohort of women with breast cancer (N = 455) divided into those invited to participate in an RCT (201 acceptances, 66 refusals) and a comparable control group not invited to participate (n = 188). All the patients underwent the same treatment (fluorouracil, epirubicin, and cyclophosphamide 100 mg/m2 for six cycles). One and 7 months after the beginning of chemotherapy, self-administered satisfaction scores were used to compare the women's assessment of their care (Comprehensive Assessment of Satisfaction with Care validated scale). RESULTS: At the beginning of chemotherapy, women to whom RCT had been proposed rated the doctors' availability (average +/- standard deviation [SD]: RCT acceptance group, 3.60 +/- 0.78; RCT refusal group, 3.68 +/- 0.87; control group, 3.41 +/- 0.82; P < or = .02) and the doctors' communication (average +/- SD: RCT acceptance group, 3.56 +/- 0.88; RCT refusal group, 3.67 +/- 0.88; control group, 3.39 +/- 0.84; P .05) higher than those to whom the trial was not proposed. After the treatment, participants in the RCT felt that their doctor was more supportive (average +/- SD: RCT acceptance group, 3.04 +/- 0.92; control group, 2.77 +/- 0.85; P = .005) and more informative about their illness and treatment (average +/- SD: RCT acceptance group, 3.34 +/- 0.88; control group, 3.08 +/- 0.92; P = .006) than those in the control group. The general level of satisfaction was also higher in the RCT acceptance group. CONCLUSION: Women participating in an RCT have a more positive picture of their doctors' care than others, probably because of the structural effects of the informed consent and data collection processes.

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer.

As there is a risk for relapse in early breast cancer, especially at 1-3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the optimal treatment strategy (i.e., initial adjuvant aromatase inhibitor therapy or sequential adjuvant aromatase inhibitor therapy).

Decision-making and breast cancer clinical trials: how experience challenges attitudes.

OBJECTIVE: The aim of this study was to measure women's preferences about decision-making and their impact to participate or not to a hypothetical randomised controlled trial (RCT). METHODS: We surveyed prospectively breast cancer patients invited to participate in a clinical RCT (group 1a=201 acceptances, group 1b=66 refusals) or not invited (group 2=188). All women had the same treatment. RESULTS: Decision-making preferences of patients who had refused clinical RCT entry were more patient's centred (72.3%) compared to those of patients who accepted (35.0%, P<0.001). Altruism was not a significant determinant of patients' participation. Randomisation was considered acceptable in 52.0% (group 1a) compared to 16.9% and 21.1% for group 1b or group 2, respectively (P<0.001). It was the main predictor of willingness to participate in a hypothetical RCT (adjusted odds ratio (OR(adj)) 4.6; 95% confidence interval [2.7-7.7]; P<0.001) with the patient group allocation (OR(adj) group 1a=5.0 [2.9-8.7]; group 1b=0.2 [0.0-0.8]; group 2=1 [referent]; P<0.001). After multivariate adjustment, willingness to participate was also significantly related with medical decision-making preferences (OR(adj) 2.2 [1.0-4.9]; P=0.045), with the feeling of being unable to refuse a doctor's proposal (OR(adj) 1.8 [1.1-3.2]; P=0.031), and with satisfaction with doctors' communication (OR(adj) 3.1 [1.5-7.8]; P<0.001). CONCLUSIONS: Patients' acceptance to participate in a RCT is preferred to be doctor's decision, whereas refusal is a personal one. When proposing a RCT, doctors must deal with patients' a priori negative feelings about randomisation. They should thoroughly discuss the reasons for and importance of randomisation as well as the other aspects of participating in the trial in order to give patients all of the information they need to make an informed decision.

Effects of adjuvant aromatase inhibitor therapy on lipid profiles.

How aromatase inhibitors affect lipids is of great interest. Compared with tamoxifen, adjuvant anastrozole and letrozole are associated with increased incidences of hypercholesterolemia, while similar data are lacking for exemestane in the adjuvant setting. No significant differences in lipid profiles occurred with extended adjuvant exemestane compared with placebo, but total cholesterol and low-density lipoprotein levels increased significantly above baseline in both groups over 6 months. Likewise, no significant differences in hypercholesterolemia rates occurred between extended adjuvant letrozole and placebo. A lipid substudy further confirmed that letrozole did not significantly alter serum lipids for 36 months compared with placebo. Thus, although aromatase inhibitors lack the lipid-lowering properties of tamoxifen, no significant worsening of lipid levels occurs with their use. Patients would benefit from lifestyle changes and routine monitoring of serum lipids. Breast cancer therapy trials often report serum lipid parameters, but assessing the quality and overall significance of the data can be difficult. Methodology of data collection varies among trials and the concomitant use of lipid-modifying medication is often not reported. This review discusses the current understanding of the influence of lipid levels on cardiovascular risk in women and presents key findings on the effects of adjuvant aromatase inhibitor therapy on lipid profiles.

Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial.

PURPOSE: The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. PATIENTS AND METHODS: Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). RESULTS: Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose. CONCLUSION: Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.

Epirubicin-based chemotherapy as adjuvant treatment for poor prognosis, node-negative breast cancer: 10-year follow-up results of the French Adjuvant Study Group 03 trial.

We evaluated the contribution of an epirubicin-based adjuvant chemotherapy on disease-free survival (DFS) in poor prognosis, node-negative breast cancer (BC) patients. Poor prognostic factors were defined as: pathologic tumor size >or= 4 cm, estrogen-receptor negative, and progesterone-receptor negative. Scarff-Bloom Richardson grade 2 tumors must have two of these factors, and only one in case of grade 3. Between 1988 and 1994, 328 patients were randomized to receive either no systemic treatment (control, n = 161), or fluorouracil 500 mg/m(2), epirubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2), 6 cycles every 21 days (FEC50, n = 167), without any hormonal treatment. The median follow up was 114 months. The 10-year DFS rates were 64 and 71%, respectively (p = 0.23). In the Cox regression model, independent prognostic factors of relapse were the number of nodes examined < 10 (p = 0.002), BCS (p = 0.01), and premenopausal status (p = 0.04). In this model, the relative risk of relapse was 1.46 (CI95 %: 1.05-1.87) in favor of FEC50. In patients who underwent BCS, 21 % developed a local relapse (24 versus 18 %, respectively). The 10-year local DFS was 70.5 and 79.3 %, respectively (p = 0.27). The 10-year overall survival was not different (74.1 versus 70.7 %, p = 0.82). After 10 years of follow-up, the FEC50 regimen reduced the risk of relapse in poor-prognosis node-negative BC patients. The incidence of local relapse was high, and probably related to inclusion criteria. Epirubicin was probably underdosed in such patients, and ongoing studies using 100 mg/m(2) of epirubicin will give us the answer in a near future.

Refining the postmenopausal breast cancer treatment paradigm: the FACE trial.

It is clear that letrozole and anastrozole provide significant benefits for patients with breast cancer. However, possible differences in efficacy have been suggested by varying degrees of aromatase inhibition and effectiveness in the neoadjuvant and first-line settings. Analyses of aromatase inhibitor-treated patient subgroups within the Arimidex, Tamoxifen, Alone or in Combination trial and Breast International Group 1-98 trial, and the National Cancer Institute of Canada Clinical Trials Group's MA.17 study, have also suggested some differences in efficacy. The question is how best to maximize these differences to benefit specific patient subgroups, such as postmenopausal women with node-positive disease. Nodal status is one of the strongest prognostic factors for breast cancer recurrence and several studies have shown that patients with node-positive disease are at higher risk for early relapse. It is thought that patients at increased risk for early relapse may be better treated with an aromatase inhibitor upfront, but the guidelines are unclear as to which aromatase inhibitor should be used. To answer this important question quickly, the Femara Anastrozole Clinical Evaluation (FACE) trial is recruiting node-positive patients and randomizing them to receive either early adjuvant letrozole or early adjuvant anastrozole. The trial has been designed to differentiate between the two drugs in the shortest possible time frame by using patients at increased risk of early recurrence of breast cancer, so that the required number of events to initiate analysis will be obtained more quickly. In total, 4000 patients who have recently undergone surgery for node-positive primary breast cancer (and who have no clinical or radiological evidence of recurrent disease or metastasis) are being enrolled around the world. The FACE trial will not only provide an efficacy evaluation between these two aromatase inhibitors but also provide a valuable head-to-head comparison of the safety profiles of adjuvant letrozole and anastrozole. The data will be transferred to an independent academic organization, the Istituto Nazionale Tumori (Michelangelo Foundation, Milan, Italy), which will verify and analyze the data, removing any perception of bias. An Independent Data Monitoring Committee will then decide when and how the trial data are to be released. The results are expected to further refine the treatment paradigm for breast cancer in postmenopausal patients with node-positive disease.