A Multicenter Study to Assess a Systematic Screening of Occupational Exposures in Lung Cancer Patients.

Occupational lung cancer cases remain largely under-reported and under-compensated worldwide. In order to improve the detection and compensation of work-related lung cancers, we implemented a systematic screening of occupational exposures, combining a validated self-administered questionnaire to assess occupational exposures and a specialized occupational cancer consultation. After a pilot study, the present prospective, open-label, scale-up study aimed to assess this systematic screening of occupational exposures in lung cancer patients in five sites in France by associating university hospitals with cancer centers. Patients with lung cancer were sent a self-administered questionnaire to collect their job history and potential exposure to lung carcinogens. The questionnaire was assessed by a physician to determine if a specialized occupational cancer consultation was required. During the consultation, a physician assessed if the lung cancer was occupation-related and, if it was, delivered a medical certificate to claim for compensation. Patients were offered help from a social worker for the administrative procedure. Over 15 months, 1251 patients received the questionnaire and 462 returned it (37%). Among them, 176 patients (38.1%) were convened to the occupational cancer consultation and 150 patients attended the consultation. An exposure to occupational lung carcinogen was identified in 133 patients and a claim for compensation was judged possible for 90 patients. A medical certificate was delivered to 88 patients and 38 patients received compensation. Our national study demonstrated that a systematic screening of occupational exposures is feasible and will bring a significant contribution to improve the detection of occupational exposures in lung cancer patients.

Pattern and risk factors of isolated local relapse among women with hormone receptor-positive and HER2-negative breast cancer and lymph node involvement: 10-year follow-up analysis of the PACS 01 and PACS 04 trials.

PURPOSE: We aimed to determine the pattern of isolated local recurrences (ILR) in women with stage II-III hormone receptor-positive and human epidermal growth factor receptor 2 breast cancer (HR + /HER2-BC) after 10-year follow-up. METHODS: UNICANCER-PACS 01 and PACS 04 trials included 5,008 women with T1-T3 and N1-N3 to evaluate the efficacy of different anthracycline ± taxanes-containing regimens after modified mastectomy or lumpectomy plus axillary lymph node dissection. We analyzed the data from 2,932 women with HR + /HER2- BC to evaluate the cumulative incidence of ILR and describe the factors associated with ILR. RESULTS: After a median follow-up of 9.1 years (95% CI 9.0-9.2 years), the cumulative incidence of ILR increased steadily between 1 and 10 years from 0.2% to 2.5%. The multivariable analysis showed that older age (subhazard ratios [sHR] = 0.95, 95% CI 0.92-0.99) and mastectomy (sHR = 0.39, 95% CI 0.17-0.86) were associated with lower risk of ILR, and no adjuvant endocrine therapy (sHR = 2.73, 95% CI 1.32 7-5.67) with increased risk of ILR. CONCLUSION: In this population of high-risk patients with localized HR + /HER2- BC, the risk of ILR was low but remained constant over 10 years. Younger age at diagnosis, breast-conserving surgery, and adjuvant endocrine therapy were independent risk factors of ILR.

[Cancers induced by occupational exposure: What progress has been made?] / Les cancers induits par les expositions professionnelles : les progrès.

INTRODUCTION: In 2019, only 1,790 occupational cancers were recognized, i.e., less than 1% of estimated occupational cancers. Our study aims to expand the methodology of a French cancer center to improve the detection and compensation of occupational bronchopulmonary cancers. PATIENTS AND METHODS: Between November 2014 and December 2020, all patients diagnosed with primary bronchopulmonary cancer (including mesothelioma) received a free questionnaire (Curriculum Laboris) aimed at retracing their professional career but also socio-demographic data. After an initial analysis of the questionnaire, a consultation can be scheduled if exposures are suspected. They will then be confirmed or not, during a consultation of around 1hour 30minutes during which the patient's precise career path is explored. RESULTS: Among the 498 patient questionnaires received, 261 patients (52%) benefited from a consultation. Of all the patients seen in consultation, 198 (or 76%) had a proposal to declare an occupational disease. Among the 151 declarations of which the fate is known, 107 (i.e., 54% of the proposed declarations or 21% of the questionnaires concerning primary lung cancer) received an agreement of recognition. CONCLUSION: The massive underreporting of occupational cancers at present in France is a real public health problem. The two major issues in the recognition of occupational diseases are, on the one hand, reparation for the damage suffered by victims or their beneficiaries and, on the other hand, the adaptation of national prevention programs considering past, present and emerging.

UCBG 2-04: Long-term results of the PACS 04 trial evaluating adjuvant epirubicin plus docetaxel in node-positive breast cancer and trastuzumab in the human epidermal growth factor receptor 2-positive subgroup.

PURPOSE: We conducted a double-randomised phase III trial to evaluate a concomitant taxane-anthracycline regimen in node-positive breast cancer and the efficacy of trastuzumab in the human epidermal growth factor receptor 2 (HER2)-positive subpopulation. METHODS: A total of 3010 patients with node-positive breast cancer were randomly assigned to receive 6 cycles of 500 mg/m2 of fluorouracil, 100 mg/m2 of epirubicin and 500 mg/m2 of cyclophosphamide (FEC) or 75 mg/m2 of epirubicin and 75 mg/m2 of docetaxel (ED). Patients with HER2-positive tumours were secondary randomly assigned to either trastuzumab or observation. The primary end-point was disease-free survival (DFS) in the two chemotherapy arms. RESULTS: After a 115-month median follow-up, DFS was not significantly better in the ED arm (DFS: 70%, 95% confidence interval [CI]: 67-72) than in the FEC arm (DFS: 68%, 95% CI: 65-70; hazard ratio [HR] = 0.88, 95% CI: 0.77-1.01; p = 0.064). The OS was not different between FEC (OS: 80%, 95% CI: 78-83) and ED (OS: 81%, 95% CI: 79-83); HR = 0.97, 95% CI: 0.81-1.16; p = 0.729). ED appeared more toxic. In the 528 HER2-positive subset, there was trend for a higher DFS, in the intention-to-treat population, in the trastuzumab arm (DFS: 68%, 95% CI: 61-74) than in the observation arm (DFS: 60%, 95% CI: 54-66; HR = 0.77, 95% CI: 0.57-1.03; p = 0.079). In the per-protocol population, DFS was significantly higher in the trastuzumab arm (DFS: 70%, 95% CI: 63-76) than in the observation arm (DFS: 59%, 95% CI: 53-65; HR = 0.69, 95% CI: 0.51-0.94; p = 0.0156). The OS was not different between these 2 arms. CONCLUSION: This study did not show superiority of the concomitant anthracycline-taxane arm which was more toxic in high-risk node-positive breast cancer patients. Long-term results of the HER2-positive subpopulation are in line with those of the other adjuvant trastuzumab trials but quantitatively less pronounced mostly because of lack of power.

6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial.

BACKGROUND: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. METHODS: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. FINDINGS: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. INTERPRETATION: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. FUNDING: The French National Cancer Institute.

[Supportive care for survivors]. / Pour des soins de support de l'après cancer.

Advances in early detection and treatment have pushed in a few decades the management of cancers from a management model of the end of life to the management of a chronic disease. This evolution has accelerated the development of supportive care in two directions, firstly towards the best possible support to the end of life in advanced cancer patients (palliative care) and secondly to the limitation of treatment toxicities, the prevention of relapse and the return to life as "normal" as possible (care for after cancer). If palliative care now has a legitimacy and a solid regulatory base, this is not yet the case of supportive care in France. The content and organization differ depending on the institution, the choice of clinicians and patient preferences. Social networks and media convey messages that blur evidence-based practices. This article aims to review the facilitators and obstacles of this perspective.

Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106).

PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. PATIENTS AND METHODS: Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(-) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. RESULTS: At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P = .12). CONCLUSION: Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY NUMBER: NCT00055679, Agence National de Sécurité du Médicament (ANSM) - France.

Management and research in cancer treatment-related cardiovascular toxicity: Challenges and perspectives.

Cardiovascular toxicity is a potentially serious complication that can result from the use of various cancer therapies and can impact the short- and long-term prognosis of treated patients as well as cancer survivors. In addition to their potential acute cardiovascular adverse events, new treatments can lead to late toxicity even after their completion because patients who survive longer generally have an increased exposure to the cancer therapies combined to standard cardiovascular risk factors. These complications expose the patient to the risk of cardiovascular morbi-mortality, which makes managing cardiovascular toxicity a significant challenge. Cardio-oncology programs offer the opportunity to improve cardiovascular monitoring, safety, and management through a better understanding of the pathogenesis of toxicity and interdisciplinary collaborations. In this review, we address new challenges, perspectives, and research priorities in cancer therapy-related cardiovascular toxicity to identify strategies that could improve the overall prognosis and survival of cancer patients. We also focus our discussion on the contribution of cardio-oncology in each step of the development and use of cancer therapies.

["SOS SEIN 84" accelerated breast disease management: Patients satisfaction survey]. / « SOS SEIN 84 ¼ prise en charge rapide en pathologie mammaire : enquête de satisfaction des consultantes.

In case of a new breast symptom or an abnormal result of breast imaging, some women have a problem finding a quick answer to allay their anxiety. The Institut Sainte-Catherine in Avignon has set up a new form of accelerated disease management through the opening of a new dedicated consultation called SOS SEIN 84. We present the result of a prospective quality study of our first new patients.

[Methods of development of recommendations for clinical practice (RCP) and of setting-up of a platform cancer heart vessels (PTF-CHV) in the inter3C Vaucluse-Arles]. / Méthodes d'élaboration des recommandations pour la pratique clinique (RPC) et fonctionnement de la plate forme cœur vaisseaux cancer (PTF-CVC) dans l'inter3C Vaucluse pays d'Arles.

Monitoring and prevention of cardiovascular complications of anti-neoplastic treatment are currently well known for anthracyclines and trastuzumab but remain poorly implemented. The management of cardiac and vascular side effects of targeted therapies is not codified. The purpose of the platform heart-vessel cancer is to optimize the management of such complications within a small area (Vaucluse region of Arles). The platform will offer prescribers an easily accessible database, doctors performing exams standardized monitoring forms and patients a uniform follow-up. We report here the methodology of the elaboration of recommendations for clinical practice and the ways to develop the platform. After a year of active process, an analysis of the will be performed to see opportunities for improvement and dissemination on a larger scale.

[Bevacizumab and taxanes in the first-line treatment of metastatic breast cancer : overall survival and subgroup analyses of the ATHENA study in France]. / Bévacizumab et taxanes dans le traitement de première ligne du cancer du sein métastatique : survie globale et analyse de sous-groupes de l'étude ATHENA France.

The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.

Treatment patterns, clinical outcomes and health care costs associated with HER2-positive breast cancer with central nervous system metastases: a French multicentre observational study.

BACKGROUND: The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. METHODS: This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. RESULTS: 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. CONCLUSION: A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial.

BACKGROUND: Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. We did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer. METHODS: We did an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30-90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. Analyses were done in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00381901. FINDINGS: 1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1-51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6-94·9) in the 12-month group and 91·1% (89·7-92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05-1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001). INTERPRETATION: After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab. Despite the higher rates of cardiac events, 12 months of adjuvant trastuzmab should remain the standard of care. FUNDING: French National Cancer Institute.

[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.

Development and feasibility of a set of quality indicators relative to the timeliness and organisation of care for new breast cancer patients undergoing surgery.

BACKGROUND: Because breast cancer is a major public health issue, it is particularly important to measure the quality of the care provided to patients. Survival rates are affected by the timeliness of care, and waiting times constitute key quality criteria. The aim of this study was to develop and validate a set of quality indicators (QIs) relative to the timeliness and organisation of care in new patients with infiltrating, non-inflammatory and metastasis-free breast cancer undergoing surgery. The ultimate aim was to use these QIs to compare hospitals. METHODS: The method of QI construction and testing was developed by COMPAQ-HPST. We first derived a set of 8 QIs from consensus guidelines with the aid of experts and professional associations and then tested their metrological properties in a panel of 60 volunteer hospitals. We assessed feasibility using a grid exploring 5 dimensions, discriminatory power using the Gini coefficient as a measure of dispersion, and inter-observer reliability using the Kappa coefficient. RESULTS: Overall, 3728 records were included in the analyses. All 8 QIs showed acceptable feasibility (but one QI was subject to misinterpretation), fairly strong agreement between observers (Kappa = 0.66), and wide variations in implementation among hospitals (Gini coefficient < 0.45 except for QI 6 (patient information)). They are thus suitable for use to compare hospitals and measure quality improvement. CONCLUSIONS: Of the 8 QIs, 3 are ready for nationwide implementation (time to surgery, time to postoperative multidisciplinary team meeting (MDTM), conformity of MDTM). Four are suitable for use only in hospitals offering surgery with on-site postoperative treatment (waiting time to first appointment after surgery, patient information, time to first postoperative treatment, and traceability of information relating to prognosis). Currently, in the French healthcare system, a patient receives cancer care from different institutions whose databases cannot as yet be easily merged. Nationwide implementation of QIs covering the entire care pathway will thus be a challenge.

Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial.

PURPOSE: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years. PATIENTS AND METHODS: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days. Radiotherapy was mandatory after conservative surgery and tamoxifen was given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was the trial's main endpoint. Updated 8-year survival data are presented. RESULTS: With a median follow-up of 92.8 months, 639 patients experienced at least one event. A total number of 383 deaths were registered. Eight-year DFS rates were 65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse and a 25% reduction in the relative risk of death in favor of FEC-D. Significant relative risk reductions were observed in the HR-positive, HER2-positive, and Ki67 ≥20% subpopulations. CONCLUSION: Benefits for DFS and OS rates with the sequential FEC-D regimen are fully confirmed at 8 years.

[Physical activity and cancer survival]. / Activité physique et survie après cancer.

Physical activity has been shown in large cohort studies to positively impact survival in cancer survivors. Existing randomized controlled trials showed a beneficial effect of physical activity on physical fitness, quality of life, anxiety and self-esteem; however, the small sample size, the short follow-up and the lack of standardization of physical activity intervention across studies impaired definite conclusion in terms of survival. Physical activity reduces adiposity and circulating estrogen levels and increases insulin sensitivity among other effects. A workshop was conducted at the International Agency for Research on Cancer in April 2011 to discuss the role of physical activity on cancer survival and the methodology to develop multicentre randomized intervention trials, including the type of physical activity to implement and its association with nutritional recommendations. The authors discuss the beneficial effect of physical activity on cancer survival with a main focus on breast cancer and report the conclusions from this workshop.

Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.

Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC-PACS 01 randomized trial.

INTRODUCTION: The PACS01 trial has demonstrated that a docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel's benefit. METHODS: Tumor samples from 1,099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR = 0.66; 95% CI 0.47 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI 1.12 to 2.08, P = 0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR = 0.51, 95% CI 0.33 to 0.79 for Ki67-positive versus HR = 1.10, 95% CI 0.75 to 1.61 for Ki67-negative tumors, P for interaction = 0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR = 1.16, 95% CI 0.73 to 1.84); the reduction in the relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI 0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity.