Using a quality of life (QoL)-monitor: preliminary results of a randomized trial in Dutch patients with early breast cancer.

PURPOSE: The diagnosis and treatment of cancer negatively affect patients' physical, functional and psychological wellbeing. Patients' needs for care cannot be addressed unless they are recognized by healthcare providers (HCPs). The use of quality of life (QoL) assessments with feedback to HCPs might facilitate the identification and discussion of QoL-topics. METHODS: 113 patients with stage I-IIIB breast cancer treated with chemotherapy were included in this randomized controlled trial. Patients were randomly allocated to receive either usual care, or usual care with an intervention consisting of a QoL-monitor assessing QoL, distress and care needs before every chemotherapy cycle visit. Patients completed questionnaires regarding QoL, illness perceptions, self-efficacy, and satisfaction with communication. From the 2nd visit onwards, patients in the intervention arm and their HCPs received a copy of the QoL overview and results were shown in patients' medical files. Audio-recordings and patients' self-reports were used to investigate effects on communication, patient management and patient-wellbeing. A composite score for communication was calculated by summing the number of QoL-topics discussed during each consultation. RESULTS: Use of the QoL-monitor resulted in a higher communication score (0.7 topics increase per visit, p = 0.04), especially regarding the disease-specific and psychosocial issues (p < 0.01). There were no differences in patient management, QoL, illness perceptions or distress. Patients in the experimental arm (n = 60) had higher scores on satisfaction with communication (p < 0.05). CONCLUSIONS: Use of a QoL-monitor during chemotherapy in patients with early breast cancer might result in a more frequent discussion of QoL-topics, associated with high levels of patients' satisfaction.

Strong CD8+ lymphocyte infiltration in combination with expression of HLA class I is associated with better tumor control in breast cancer patients treated with neoadjuvant chemotherapy.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) in patients with early breast cancer. We investigated the prognostic and predictive role of TILs, macrophages, and HLA class 1 expression after NAC with or without the potentially immune modulating compound zoledronic acid (ZA). METHODS: Baseline tumor biopsies from 196 patients in the NEOZOTAC trial were analyzed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages), and HLA class I (HCA2/HC10) expression by immunohistochemistry and subsequently related to pCR and disease-free survival (DFS). RESULTS: A strong intratumoral CD8+ infiltration or expression of HLA class 1 by cancer cells was associated with a higher pCR rate (p < 0.05). Clinical benefit of high CD8+ T-cell infiltration was found when cancer cells expressed HLA class 1 (pCR: 21.8% vs. 6.7%, p = 0.04) but not when HLA class 1 expression was lost or downregulated (pCR: 5.9% vs. 0%, p = 0.38). Interaction analyses revealed survival benefit between HLA class 1 expression and strong CD8+ T-cell infiltration, whereas in the absence or downregulation of HLA class 1 expression, high levels of CD8+ T-cells were associated with survival disadvantage (p for interaction 0.01; hazard ratio 0.41, 95% CI 0.15-1.10, p = 0.08 and hazard ratio 7.67, 95% CI 0.88-66.4, p = 0.07, respectively). Baseline immune markers were not related to ZA treatment. CONCLUSIONS: Strong baseline tumor infiltration with CD8+ T-cells in the presence of tumoral HLA class 1 expression in patients with HER2-negative breast cancer is related to a higher pCR rate and a better DFS after NAC.

Cross-cultural comparison of breast cancer patients' Quality of Life in the Netherlands and Japan.

PURPOSE: Cultural differences are hypothesized to influence patients' Quality of Life (QoL) reports. However, there is a lack of empirical cross-cultural studies comparing QoL of patients with cancer. This study aims to compare QoL of women with breast cancer in the Netherlands and Japan, and to investigate the association of QoL with sociodemographic, clinical, and psychological variables (illness perceptions). METHODS: Dutch (n = 116) and Japanese (n = 148) women with early breast cancer undergoing chemotherapy completed the EORTC QLQ-C30 and Brief Illness Perception Questionnaire immediately before their second cycle of chemotherapy. RESULTS: Dutch women reported poorer Physical, Role, Emotional, and Cognitive functioning than Japanese women. Additionally, illness perceptions were significantly different in Japan and the Netherlands, but these did not vary across treatment type. In Japan, QoL of women receiving AC-chemotherapy was better than that of women receiving FEC-chemotherapy, whereas in the Netherlands, QoL did not vary as a function of chemotherapy. Illness perceptions about symptom severity, adverse consequences, and emotional representations were negatively related to most domains of patients' QoL in both countries. Adding illness perceptions as covariates to the ANOVA analyses rendered the effects of country and treatment type on QoL non-significant. CONCLUSIONS: Comparing Dutch and Japanese women with early breast cancer revealed important differences in treatment modalities and illness perceptions which both appear to influence QoL. Perceptions about cancer have been found to vary across cultures, and our study suggests that these perceptions should be considered when performing cross-cultural studies focusing on patient-reported outcomes.

[Clinical care pathway for chronic kidney disease : development and perspectives]. / Le trajet de soins de l'insuffisance rénale chronique : développement et perspectives.

Because of the significant costs related to the treatment of end-stage kidney disease by dialysis, Belgian Health Care Authorities proposed in June 2009 to launch an early multidisciplinary care plan for chronic kidney disease (CKD) patients in the form of a clinical care pathway (CCP) focusing on a combined follow-up by the general practitioner and the nephrologist. The objective was to increase nephro-protection measures, reduce patient morbidity and mortality, and delay admission on dialysis. Our Nephrology Department at Erasme Hospital took the opportunity of CCP to set up workshops on therapy education which promote CKD patients' compliance and autonomy regarding their treatment (" empowerment "). These workshops are conducted by a health professional together with a patient partner recruited by our team according to the model developed by the faculty of medicine at the University of Montreal. This model is based on the patient's valued experience of living with a chronic disease, a knowledge which is complementary to that acquired by any health professional. This patient partnership (PP) may also be implemented in teaching and research. In health care services, patient partners with a resource profile are involved not only in the organization of these services, but also in the development and management of health care political programs. The PP model currently developed in the Nephrology Department is part of the Quality project of our academic hospital and helps to further the co-construction of future health care networks.

Suite aux surcoûts liés au traitement de l'insuffisance rénale chronique (IRC) terminale par la dialyse, l'INAMI a proposé depuis juin 2009 une prise en charge multidisciplinaire précoce du patient IRC sous la forme d'un trajet de soins (TDS) privilégiant le suivi par le médecin généraliste en alternance avec le néphrologue. Le but est d'optimiser les mesures de néphroprotection, de réduire la morbi-mortalité des patients et de retarder leur arrivée en dialyse. Notre service a saisi cette opportunité des TDS de l'IRC pour mettre en place des ateliers d'éducation thérapeutique susceptibles de favoriser l'adhésion et l'autonomie des patients IRC vis-à-vis de leur traitement (" empowerment "). Ces ateliers sont co-animés par un professionnel de santé et un patient partenaire recruté par le service selon le modèle développé à la Faculté de Médecine de l'Université de Montréal. Le partenariat patient (PP) s'appuie sur les savoirs expérientiels reconnus des patients, complémentaires aux savoirs professionnels, issus de la vie avec la maladie et acquis par la pratique des soins et des services de santé. Il peut aussi se développer dans l'enseignement et la recherche. En milieux de soins, il s'agit de patients partenaires au profil ressource, partenaires dans les soins directs, mais aussi dans l'organisation des services, la gouvernance et l'élaboration des politiques de santé. Ce modèle, en cours d'implémentation dans le Service de Néphrologie de l'Hôpital Erasme, fait partie du projet qualité institutionnel et tend vers la co-construction des milieux de soins de demain.

[Diagnosis and treatment of nephrolithiasis and prevention of recurrences]. / Mise au point et traitement des lithiases rénales et prévention des récidives.

INTRODUCTION: despite fluctuations, the prevalence of nephrolithiasis has significantly increased during the last decades in industrialized nations worldwide (1 to 15 %), which has a significant impact on the cost of healthcare. This increased prevalence is mainly explained by diet modifications. Environmental, metabolic and genetic factors may also influence the formation of kidney stones. As a consequence, the medical management of this disease is preferentially multidisciplinary and involves urologists, nephrologists, radiologists, biologists and dietitians. Urological management : may be mandatory during any acute and/or remote phase of an episode of renal colic, in case of residual stones. Several techniques are available: insertion of double J stent, extracorporeal shock wave lithotripsy, ureteroscopy (flexible or rigid), percutaneous nephrolithotomy and more occasionally, open surgery. Nephrological management: is justified in the course of the acute episode and aims to identify the causal factor(s) of kidney stones formation. The diagnostic approach involves a thorough interrogation (personal medical and surgical history, details of the kidney stone disease and family medical history) as well as a metabolic assessment. Moreover, given the high rate of recurrence (about 50 % within 5 to 10 years), individualized secondary prevention measures are necessary. The recommendations should take into account the identified risk factors and any metabolic abnormalities.

INTRODUCTION: la néphrolithiase est une affection dont la prévalence (1 à 15 %) a beaucoup augmenté ces dernières décennies dans les pays industrialisés et a, de ce fait, un impact sur les dépenses en soins de santé. Cette augmentation de prévalence s'explique essentiellement par une modification des habitudes alimentaires. La survenue d'une néphrolithiase peut en outre, être influencée par des facteurs environnementaux, métaboliques voire génétiques. La prise en charge de cette affection est le plus souvent pluridisciplinaire, impliquant urologues, néphrologues, radiologues, biologistes et diététiciens. La prise en charge urologique peut être nécessaire en phase aiguë et/ou à distance de l'épisode de colique néphrétique, pour l'élimination éventuelle de calculs résiduels. Plusieurs techniques sont disponibles : la mise en place de sondes double J, la lithotritie extracorporelle, l'urétéroscopie (souple ou rigide) voire la néphrolithotomie percutanée et plus rarement la chirurgie ouverte. La prise en charge néphrologique est justifiée au décours de l'épisode aigu et vise à identifier la ou les cause(s) ayant conduit à la formation de calculs. La démarche diagnostique comporte un interrogatoire approfondi (antécédents personnels médicaux et chirurgicaux, histoire de la maladie lithiasique et antécédents familiaux) et un bilan métabolique. Par ailleurs, compte-tenu du taux élevé de récidive (environ 50 % dans les 5 à 10 ans), la mise en place de mesures individualisées de prévention secondaire est nécessaire. Ces recommandations doivent tenir compte des facteurs de risque identifiés et des éventuelles anomalies du bilan métabolique.

[Not Available]. / Implémentation des trajets de soins de l'insuffisance rénale chronique: bénéfices pour le patient et perspectives en termes de santé publique.

Because of the significant costs related to the treatment of end-stage kidney disease by dialysis, Belgian Health Care Authorities proposed in June 2009 an early multidisciplinary care of the chronic kidney disease (CKD) in a so-called clinical pathway (CP). Working on the hypothesis that inclusion into a CP could result in reduced morbidity and mortality and delayed admission on dialysis, we initiated a retrospective cohort study on dialyzed patients for whom a prior CKD diagnosis was made between June 1, 2009 and August 31, 2013 in the Nephrology Dept of Erasme Hospital. The exposed patient group was defined as enrolled patients into a CP (n = 25), the control patients were free of any CP (n = 25). Survival analyses were performed to search for an association between the inclusion into a CP and the time period needed to reach dialysis, but also to find a possible impact of CP on mortality and risk of hospitalization. The present study showed that CKD-CP significantly delayed the time of dialysis initiation (HR = 0.48 [0.27-0.87]; p = 0.015) but also reduced mortality (HR = 0.10 [0.02-0.53]; p = 0.007) and hospitalization risk (HR = 0.30 [0.11-0.83]; p = 0.020) after starting dialysis. These data suggest the benefit of a multidisciplinary care of CKD patients. However, a larger scale study is necessary to confirm these results.

Dynamic prediction in breast cancer: proving feasibility in clinical practice using the TEAM trial.

BACKGROUND: Predictive models are an integral part of current clinical practice and help determine optimal treatment strategies for individual patients. A drawback is that covariates are assumed to have constant effects on overall survival (OS), when in fact, these effects may change during follow-up (FU). Furthermore, breast cancer (BC) patients may experience events that alter their prognosis from that time onwards. We investigated the 'dynamic' effects of different covariates on OS and developed a nomogram to calculate 5-year dynamic OS (DOS) probability at different prediction timepoints (tP) during FU. METHODS: Dutch and Belgian postmenopausal, endocrine-sensitive, early BC patients enrolled in the TEAM trial were included. We assessed time-varying effects of specific covariates and obtained 5-year DOS predictions using a proportional baselines landmark supermodel. Covariates included age, histological grade, hormone receptor and HER2 status, T- and N-stage, locoregional recurrence (LRR), distant recurrence, and treatment compliance. A nomogram was designed to calculate 5-year DOS based on individual characteristics. RESULTS: A total of 2602 patients were included (mean FU 6.2 years). N-stage, LRR, and HER2 status demonstrated time-varying effects on 5-year DOS. Hazard ratio (HR) functions for LRR, high-risk N-stage (N2/3), and HER2 positivity were HR = (8.427 × 0.583[Formula: see text], HR = (3.621 × 0.816[Formula: see text], and HR = (1.235 × 0.851[Formula: see text], respectively. Treatment discontinuation was associated with a higher mortality risk, but without a time-varying effect [HR 1.263 (0.867-1.841)]. All other covariates were time-constant. DISCUSSION: The current nomogram accounts for elapsed time since starting adjuvant endocrine treatment and optimizes prediction of individual 5-year DOS during FU for postmenopausal, endocrine-sensitive BC patients. The nomogram can facilitate in determining whether further therapy will benefit an individual patient, although validation in an independent dataset is still needed.

CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects.

Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored.

Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01).

This side study investigated the effect of chemotherapy on thyroid function and the extent to which it can predict pathological complete response (pCR) in patients with early breast cancer taking part in NEOZOTAC phase III trial, randomizing between neoadjuvant chemotherapy with or without additional zoledronic acid. Moreover, we examined the impact of thyroid function on toxicity. Serum samples of 38 patients were available for analyses. Free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were compared between baseline and before the 6th cycle and between subjects with and without pCR. The relation between toxicity and the variation in fT4 and TSH levels during chemotherapy was tested. Samples at baseline and before the 6th cycle were available for 31 and 21 patients, respectively. The mean baseline fT4 level was 16.0 pmol/L and TSH level 1.11 mU/L, and these did not differ between both arms at each time point. During six cycles of chemotherapy, fT4 levels decreased (p = 0.0001), and TSH levels increased significantly (p = 0.019). Interestingly, the decrease of fT4 was significantly greater in patients without nausea, vomiting, or neuropathy, than in patients with those side effects (p = 0.037, p = 0.043, and p = 0.050, respectively). Baseline TSH levels tended to be higher in patients with pCR (p = 0.035 univariate analysis and p = 0.074 multivariate analysis). Chemotherapy blunts thyroid function, which was associated with less side effects. These data urge further evaluation of the effects of thyroid function on toxicity and outcome of breast cancer therapy.

Healthcare utilisation in patients with breast cancer or non-Hodgkin lymphoma who experienced febrile neutropenia in the Netherlands: a retrospective matched control study using the PHARMO database.

Few data have been published on healthcare resource utilisation associated with chemotherapy-induced febrile neutropenia (FN) in Europe. Using the PHARMO record linkage system, we identified incident adult patients with a primary hospital discharge diagnosis of breast cancer (BC) or non-Hodgkin lymphoma (NHL) from 1998 to 2008. Patients who experienced FN were matched 1:2 non-FN reference patients. Of 1033 BC patients, 80 (8%) had FN and were matched with 160 reference patients; and of 486 NHL patients, 95 (20%) had FN and 89 were matched with 178 reference patients. Significantly more FN patients were hospitalised for any cause than reference patients: BC, 81% vs. 24% (OR 12.6; 95% CI 5.7-27.8); NHL, 82% vs. 44% (OR 6.7; 95% CI 3.3-13.9). Median length of all-cause hospitalisation stay was higher for FN patients: BC, 4.0 vs. 1.0 days; NHL, 8.5 vs. 1.8 days. The median (interquartile range) number of medication treatments was higher for FN patients: BC, 5.5 (4.0-7.5) vs. 2.0 (2.0-4.0); NHL, 8.0 (5.0-11.0) vs. 3.0 (2.0-4.0). In conclusion, FN in patients with BC or NHL had increased healthcare utilisation compared with non-FN patients; thus, efforts to reduce FN are warranted to reduce cost and improve outcomes.

[Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update]. / Anticorps anti-EPN et anti-PLA2R dans les glomerulopathies extramembraneuses: le point en 2014.

Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined.

[Recurrent episodes of brushite nephrolithiasis revealing primary hyperparathyroidism]. / Néphrolithiases récurrentes de brushite révélant une hyperparathyroïdie primaire.

INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes.

Immunological subtypes in breast cancer are prognostic for invasive ductal but not for invasive lobular breast carcinoma.

BACKGROUND: Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential. METHODS: Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery. RESULTS: No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC. CONCLUSIONS: Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.

A randomized phase III study comparing pegylated liposomal doxorubicin with capecitabine as first-line chemotherapy in elderly patients with metastatic breast cancer: results of the OMEGA study of the Dutch Breast Cancer Research Group BOOG.

BACKGROUND: Prospective data on chemotherapy for elderly patients with metastatic breast cancer (MBC) remain scarce. We compared the efficacy and safety of first-line chemotherapy with pegylated liposomal doxorubicin (PLD) versus capecitabine in MBC patients aged ≥65 years in a multicentre, phase III trial. PATIENTS AND METHODS: Patients were randomized to six cycles of PLD (45 mg/m(2) every 4 weeks) or eight cycles of capecitabine (1000 mg/m(2) twice daily, day 1-14 every 3 weeks). RESULTS: The study enrolled 78 of the planned 154 patients and was closed prematurely due to slow accrual and supply problems of PLD. Many included patients were aged ≥75 years (54%) and vulnerable (≥1 geriatric condition: 71%). The median dose intensity was 85% for PLD and 84% for capecitabine, respectively. In both arms, the majority of patients completed at least 12 weeks of treatment (PLD 73%; capecitabine 74%). After a median follow-up of 39 months, 77 patients had progressed and 62 patients had died of MBC. Median progression-free survival was 5.6 versus 7.7 months (P = 0.11) for PLD and capecitabine, respectively. Median overall survival was 13.8 months for PLD and 16.8 months for capecitabine (P = 0.59). Both treatments were feasible, grade 3 toxicities consisting of fatigue (both arms: 13%), hand-foot syndrome (PLD: 10%; capecitabine: 16%), stomatitis (PLD: 10%; capecitabine: 3%), exanthema (PLD: 5%) and diarrhoea (PLD: 3%; capecitabine: 5%). Only 1 of 10 patients aged ≥80 years completed chemotherapy, while 3 and 6 patients discontinued treatment due to toxicity or progressive disease, respectively. CONCLUSION: Both PLD and capecitabine demonstrated comparable efficacy and acceptable tolerance as first-line single-agent chemotherapy in elderly patients with MBC, even in vulnerable patients or patients aged ≥75 years. However, patients aged ≥80 years were unlikely to complete chemotherapy successfully. CLINICAL TRIAL NUMBERS: EudraCT 2006-002046-10; ISRCTN 11114726; CKTO 2006-09; BOOG 2006-02.

Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01).

BACKGROUND: The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before. PATIENTS AND METHODS: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status. RESULTS: Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms. CONCLUSIONS: Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

[Estimation of the glomerular filtration rate in 2014 by tests and equations: strengths and weaknesses]. / L'estimation de la filtration glomérulaire en 2014: intérêts et limites des tests et formules.

The accurate estimation of the glomerular filtration rate (GFR) is a goal of multiple interests regarding clinical, research and public health aspects. The strong relationship between progressive loss of renal function and mortality underlines the need for early diagnosis and close follow-up of renal diseases. Creatinine is the commonest biomarker of GFR in use. By reason of non-renal determinants of GFR, it is required to integrate creatinine values within equations that take in account its most important determinants (i.e., age, sex). The CKD-EPI 2009 equation is now recommended as the first line equation to estimate GFR within the general population. In this indication, it should replace MDRD that tends to overestimate the prevalence of stage 3 chronic kidney disease with GFR around 60 ml/min. However, many questions remain about the accuracy of GFR equations in specific situations such as extremes of age or body weight. The identification of new biomarkers, less determined by non-renal determinants, is of importance. Among these biomarkers, cystatin-C is more accurate to estimate GFR when it is combined to creatinine (i.e., equation CKD-EPI 2012). However the indica. tions for using cystatin-C instead of creatinine alone are still unclear and its use remains limited in routine practice. In conclusion, neither biomarker nor equation gives an accurate estimation for the whole range of GFR and for all patient populations. Limits of prediction are relying on both biomarker's properties and the range of GFR that is concerned, but also rely on the measurement methods. Therefore, it is crucial to interpret the estimated GFR according to the strengths and weaknesses of the equation in use.

Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer.

BACKGROUND: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. PATIENTS AND METHODS: Trade-offs from 241 women were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated ACA utilities, the relative importance of each treatment property was calculated and a benefit/drawback ratio between the importance of the efficacy versus that of the side-effects and other treatment properties. Nonadherence was assessed through composites of validated self-report measures. RESULTS: Efficacy was most important. The side-effects joint and muscle pain and risk of endometrial cancer were almost as important. The benefit/drawback ratio showed 16% of the women to value the efficacy less than the side-effects and other treatment properties. A higher benefit/drawback ratio was associated with decreased nonadherence [adjusted odds ratio (OR) 0.1, 95% confidence interval 0.03-0.3]. CONCLUSIONS: One in six women do not consider the efficacy of endocrine therapy to outweigh its drawbacks. Knowing women's trade-offs is likely to identify women at risk for nonadherence and to help clinicians in tailoring their communication and care to different needs of individual women.

Reliability of core needle biopsy for determining ER and HER2 status in breast cancer.

BACKGROUND: Several studies have assessed the concordance of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status between core needle biopsy (CNB) and resection specimens, usually in small patient series and with discordant results. PATIENTS AND METHODS: ER and HER2 status determined on CNB and tissue micro-arrays of resected tumors were compared for patients treated at the Leiden University Medical Center (LUMC). When results were discordant, whole-sized slides were analyzed. Additionally, literature was searched for published patient series and combined with our data to assess the concordance of ER and HER2 determination between CNB and resection specimens. RESULTS: In the LUMC series, concordance for ER status was 99.1%. Combined concordance from 20 studies and the LUMC patient series was 93.7%. For HER2 testing, concordance was 96.2% for patients in the LUMC series. Our study and three others have investigated the concordance when HER2 was determined according to the American Society of Clinical Oncology and College of Pathology guidelines and overall concordance was 97.8%. CONCLUSIONS: Concordance between CNB and surgical specimens was high for both ER and HER2 testing. However, we recommend retesting ER-negative CNB results on the surgical specimen and performing in situ hybridization assays on HER2 immunohistochemistry 3+ CNBs to confirm HER2 status.

CYP2D6 genotype in relation to tamoxifen efficacy in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial.

The clinical importance of CYP2D6 genotype as predictor of tamoxifen efficacy is still unclear. Recent genotyping studies on CYP2D6 using DNA derived from tumor blocks have been criticized because loss of heterozygosity (LOH) in tumors may lead to false genotype assignment. Postmenopausal early breast cancer patients who were randomized to receive tamoxifen, followed by exemestane in a large randomized controlled trial were genotyped for five CYP2D6 alleles. CYP2D6 genotypes and phenotypes were related to disease-free survival during tamoxifen use (DFS-t) in 731 patients. By analyzing microsatellites flanking the CYP2D6 gene, patients whose genotyping results were potentially affected by LOH were excluded. In addition, exploratory analyses on 24 genetic variants of other metabolic enzymes and the estrogen receptor were performed. For the CYP2D6 analysis, only 2.3 % of the samples were excluded, because influence of LOH could not be ruled out. No association was found between the CYP2D6 genotype or predicted phenotype and DFS-t (poor vs. extensive metabolizers: unadjusted hazard ratio 1.33, 95 % CI 0.52-3.43; P = 0.55). DFS-t was associated with UGT2B15*2 (Vt/Vt + Wt/Vt vs. Wt/Wt: adjusted hazard ratio 0.47, 95 % CI 0.25-0.89; P = 0.019) and the estrogen receptor-1 polymorphism ESR1 PvuII (gene-dose effect: adjusted hazard ratio 1.63, 95 % CI 1.04-2.54; P = 0.033). In postmenopausal early breast cancer patients treated with adjuvant tamoxifen followed by exemestane neither CYP2D6 genotype nor phenotype did affect DFS-t. This is in accordance with two recent studies in the BIG1-98 and ATAC trials. Our study is the first CYP2D6 association study using DNA from paraffin-embedded tumor tissue in which potentially false interpretation of genotyping results because of LOH was excluded. Polymorphisms in the estrogen receptor-1 and UGT2B15 may be associated with tamoxifen efficacy, but these findings need replication.

Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer.

AIM: The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. METHOD: All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status (SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. RESULTS: Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. CONCLUSION: Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy.