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Resume Introduction L’adjonction du palbociclib a l’hormonotherapie ameliore la survie sans progression chez les patients atteints d’un cancer du sein metastatique positif aux recepteurs hormonaux. Cette nouvelle therapie ciblee expose cependant les patients a une toxicite hematologique severe pouvant conduire a un report ou un arret du traitement et donc potentiellement a une baisse de son efficacite. L’objectif de cette etude etait d’identifier les facteurs predictifs d’hematotoxicite chez ces patients. Methodes Cette etude retrospective a inclus tous les patients ayant initie un traitement de palbociclib pour un cancer du sein metastatique positif aux recepteurs hormonaux entre le 1er decembre 2016 et le 1er janvier 2019. Toutes les donnees ont ete collectees via les dossiers electroniques ou papiers. Une hematotoxicite precoce et severe a ete definie comme l’apparition d’une toxicite hematologique grade 4 ou grade 3 ayant necessite une reduction de dose durant les trois premiers cycles. Resultats Cent quatre-vingt-un patients ont ete inclus. Quarante-six patients (25,4 %) ont developpe une hematotoxicite severe et precoce. Apres analyse multivariee, les facteurs predictifs de cette hematotoxicite sont le Performance Status de l’OMS superieur ou egal a 2 (p = 0,024) et des antecedents de radiotherapie osseuse dans l’annee (p = 0,003). Un taux de neutrophiles inferieur a 3,37 g/L avant la mise en place du palbociclib est egalement un facteur predictif de developper une hematotoxicite avec une sensibilite de 76 % et une specificite de 71 %. Conclusion Le Performance Status, les antecedents de radiotherapie osseuse dans l’annee et un taux bas de neutrophiles avant traitement sont associes a une augmentation du risque d’hematotoxicite chez les patients traites pour un cancer du sein metastatique.

Background: Persistence of unhealthy behaviors may adversely affect breast cancer (BC) outcomes and quality of life. Cancer diagnosis can represent a teachable moment and a powerful catalyst to correct such behaviors. It has been suggested that some cancer patients (pts) may be motivated towards a healthier lifestyle, particularly in case of a worse cancer-related prognosis. In this study we aimed at understanding the evolution and barriers in adoption of health behaviors after BC. Methods: We analyzed 8580 pts enrolled from 2012-2015 in a nationwide, multicenter study of stage I-III BC (CANTO, NCT01993498). Pts were longitudinally assessed at diagnosis (baseline), year(y)1 and y2 post-diagnosis. Recreational physical activity (PA) was reported using the GPAQ-16. An unhealthy smoking behavior was defined as active smoker status and an unhealthy alcohol behavior as consumption of ≥1 drink/day at y1 and y2. First, we described the longitudinal evolution of health behaviors. Then, we examined factors associated with health behaviors, to define pts that fail to adopt healthy lifestyle changes. Random effect mixed models evaluated changes in PA over time. Logistic regression models estimated odds of unhealthy smoke and alcohol behavior at y1 and y2. All models were adjusted for tumor, including BC stage, clinico-behavioral and treatment characteristics. Results: Mean age at diagnosis was 55 y (SD 11), 9% pts had stage III BC, 49% were overweight/obese (body mass index [BMI] ≥25 Kg/m2), 41% did not meet PA recommendations (0.05 at both time points). Among pts who were active smokers at baseline, 37% at y1 and 30% at y2 reported reduced tobacco, and among those who used to have ≥1 drink/day at baseline, 11% at y1 and 8% at y2 reported reduced alcohol consumption. 11% pts at y1 and 12% pts at y2 had unhealthy smoke behavior whereas 13% pts at y1 and 14% pts at y2 had unhealthy alcohol behavior (Cochran-Armitage trend test: p=0.034 for smoke and p=0.193 for alcohol). Older age (adjusted odds ratio [aOR] for a 5-year increase in age, 0.69 [95%CI 0.66-0.73]) and being in a relationship (aOR vs not, 0.66 [95% CI 0.54-0.82]) were associated with reduced odds of unhealthy smoke behavior, although older pts (aOR for a 5-year increase in age, 1.34 [95%CI 1.22-1.40]) and those in a relationship (aOR vs not, 1.35 [95% CI 1.10-1.68]) were also more prone to unhealthy alcohol behavior. Lower BMI was consistently associated with higher odds of unhealthy smoke and alcohol behavior (aOR for each decreasing BMI unit: for smoke behavior, 1.05 [95%CI 1.03-1.07]; for alcohol behavior, 1.02 [95% CI 1.01-1.04]). BC stage was not associated with smoke and alcohol behavior. Conclusions: This large clinical study suggests that a substantial proportion of pts pursue a healthy lifestyle after BC. However, there are still survivors that fail to adopt positive and durable lifestyle changes. Uptake of increased levels of PA was not homogenous in this cohort, and we found an upward trend in unhealthy smoke behavior and steady rates of unhealthy alcohol behavior over time. We defined diverse behavioral profiles of pts, according, among others, to age, social status, BMI and BC characteristics. These data will help better inform targeted lifestyle interventions to improve health behaviors after BC. Citation Format: Antonio Di Meglio, Arnauld S Gbenou, Elise Martin, Laurence Vanlemmens, Charles Guenancia, Olivier Rigal, Marion Fournier, Patrick Soulie, Marie-Ange Mouret-Reynier, Carole Tarpin, Florence Boiffard, Sophie Guillermet, Sibille Everhard, Anne-Laure Martin, Sylvie Giacchetti, Thierry Petit, Florence Dalenc, Philippe Rouanet, Antoine Arnaud, Fabrice Andre, Ines Vaz-Luis. Lifestyle changes after breast cancer: A prospective study among 8580 women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-03.

Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue (p = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up (p = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet&ndash, exercise supportive care in this population, focusing on precarious patients.

Purpose Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in “intermediate” clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients. Methods This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes. Results One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2–42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2–34.8]) and added in 15 (7.5% [3.8–11.2]. 6 changes (8%) were based on patients’ decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p, Highlights • EndoPredict ® (EpClin) allowed a chemotherapy decision modification in 35% of the patients included in the Adendom trial. • Patient-physician concertation is important: 8% of treatment changes are based on patients’ will. • A single-step decision including the test appears preferable to limit anxiety and distress.

Metastatic breast cancer (MBC) patients experience long survival and report poorer quality of life than localized breast cancer patients. Comprehensive supportive care (CSC) has been shown to improve the quality of life (QoL) of MBC. The respective part of each support care has not been fully examined, and little is known about whether meeting patients’ needs is accompanied by decreased unscheduled hospital care (UHC). This prospective monocentric study included women who started a new treatment line for MBC between January 2018 and December 2018. The endpoints were factors associated with UHC and QoL (SF36) at month 12. 100 patients were offered CSC, 78 were included (21 refusals, 1 no MBC). CSC was provided to 60 patients: pain (43%), psychological (37%), kinesitherapy (30%), social assistance (22%), esthetic (18%), nutrition (18%), massage (13%), and none (10%). CSC rate was not statistically different among patients with (58%) and without UHD (49%). Factors associated with a decrease of UHC were age > 65 years (p = 0.01), no previous treatment for MBC (p = 0.0001) with a trend for the lack of CSC (p = 0.054). Among the 8 domains of the SF36 scale, only health change perception was improved (p = 0.01) and its predictive factors were treatment carried out as planned (p = 0.0004), pain care (p = 0.003), and lack of MBC progression (p = 0.0035). CSC can improve QoL in MBC. Painful patients might benefit more from CSC. UHC did not decrease for patients receiving CSC as expected possibly because of their important needs for clinical care.

Background There is no large prospective trial assessing mid-term adverse effects of adjuvant chemotherapy. In order to address this question, we developed CANTO (CANcer TOxicities - NCT01993498 - http://etudecanto.org/), a prospective trial dedicated to the quantification of side effects after treatment for patients with early breast cancer and to develop predictors of such toxicities. The aim of this presentation is to assess chemotherapy (CT) practice and to report toxicities that persist 3-6 months after CT. Methods CANTO is a prospective study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients (pts) of 26 French comprehensive cancer centers. The study has included 10 500 patients at the time of submission. Pts are assessed at diagnosis, 3-6, 12, 36, 48 and 60 months after treatment completion. CANTO collects >100 items related to toxicities. In the current study, we focus on the first set of data available from the trial (1st database lock, n=6090). We here assess CT practice and toxicities at 3 months. Results Information about (neo)adjuvant CT (NACT/ACT) is available in 5805 pts (96%). Median age at diagnosis was 57y (22-93). Pts had HR+/HER2-, HER2+ or triple negative (TN) tumors in 74%, 15% and 11% of cases. Ki67 was assessed in 70%, and genomic tests in 1% of pts, respectively. Overall, 3074 pts (53%) received CT, either adjuvant (ACT: 76%) or neoadjuvant (NACT: 24%). ACT/NACT pts (84%) received a sequential anthracyclines–taxanes based 6 courses CT schedule. CT was administered in 44.7%, 87.2% and 92.3% of HR+/HER2+/TN tumors, respectively. ACT was administered in 73.2% of pT2+ pts (vs 36.0% in pT0-1 – p We focus here on clinically most relevant patient reported symptoms at 3 m (any grade). side effects at 3m no CT (%)CT (%)p valuePain76.682.1 Pain complaint was recorded in 3596 pts (97.2% of pts with available data), with a median value of 4 on the VAS (range 1-10). In ACT/NACT pts, muscle and joint pain were predominant. Neurological symptoms were seen in 3024 pts (59%), the most frequent pertaining to cognitive disorder (attention trouble, CT: 61.2% vs noCT: 56% - p=.06) and peripheral neuropathy (overall 31%). Paresthesias and sensory neuropathy were much more frequent in CT vs noCT pts: respectively 37.3% vs 20.3% and 25.7% vs 12.8% (both p Conclusions In this real life, prospective cohort, CT is frequently prescribed and appears in good compliance with current guidelines. Overall, symptoms burden at treatment completion is strikingly high, and much higher in pts receiving CT. A special attention should be given to pain and neurological symptoms. Dedicated questionnaires and sub-studies will explore in depth these side effects. Extended analyses of CT practice and toxicities will be presented. Citation Format: Cottu PH, Amar Y, Pistilli B, Bonsang-Kitzis H, Lesur A, Lerebours F, Vanlemmens L, Tredan O, Levy C, Jouannaud C, Fournier M, Soulie P, Rigal O, Giacchetti S, Arnaud A, Arsene O, Savignoni A, Mesleard C, Andre F, Arveux P. CANTOCHEM: Analysis of chemotherapy practice and early side effects in the 6090 first patients from the prospective CANTO cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-18.

Background In early breast cancer (BC), there has been a trend to escalate endocrine therapy (ET) and to de-escalate chemotherapy (CT). However, the impact of ET versus CT on the quality of life (QoL) of early BC patients is unknown. Here, we characterize the independent contribution of ET and CT on patient-reported outcomes (PROs) at 2 years after diagnosis. Patients and methods We prospectively collected PROs in 4262 eligible patients using the European Organization for Research and Treatment of Cancer QLQ-C30/BR23 questionnaires inside CANTO trial (NCT01993498). The primary outcome was the C30 summary score (C30-SumSc) at 2 years after diagnosis. Results From eligible patients, 37.2% were premenopausal and 62.8% postmenopausal; 81.9% received ET and 52.8% CT. In the overall cohort, QoL worsened by 2 years after diagnosis in multiple functions and symptoms; exceptions included emotional function and future perspective, which improved over time. ET (Pint = 0.004), but not CT (Pint = 0.924), had a persistent negative impact on the C30-SumSc. In addition, ET negatively impacted role and social function, pain, insomnia, systemic therapy side-effects, breast symptoms and further limited emotional function and future perspective recovery. Although CT had no impact on the C30-SumSc at 2-years it was associated with deteriorated physical and cognitive function, dyspnea, financial difficulties, body image and breast symptoms. We found a differential effect of treatment by menopausal status; in premenopausal patients, CT, despite only a non-significant trend for deteriorated C30-SumSc (Pint = 0.100), was more frequently associated with QoL domains deterioration than ET, whereas in postmenopausal patients, ET was more frequently associated with QoL deterioration, namely using the C30-SumSc (Pint = 0.004). Conclusion(s) QoL deterioration persisted at 2 years after diagnosis with different trajectories by treatment received. ET, but not CT, had a major detrimental impact on C30-SumSc, especially in postmenopausal women. These findings highlight the need to properly select patients for adjuvant ET escalation.

International audience; Ameloblastomas are uncommon locally aggressive tumors of odontogenic epithelium that rarely metastasize. Currently, there is no standard of care for the metastatic forms. Several studies have shown that ameloblastomas frequently have a BRAF mutation.Case presentation: We report a case of a 33-year-old Caucasian woman with ameloblastoma diagnosed 30 years ago who developed lung metastasis 19 years ago. Systemic oral treatment with vemurafenib, a BRAF inhibitor, was initiated 28 months ago within the AcSé French basket clinical trial of vemurafenib.Conclusions: The patient has shown a durable clinical, functional, and radiographic partial response with vemurafenib. These observations suggest the possibility of introducing neoadjuvant and/or adjuvant targeted therapy in locally advanced ameloblastoma to improve outcome. BRAF inhibition has proved to be an efficient strategy in patients with a BRAF-mutated ameloblastoma.

5507 Background: Endometrial carcinoma is generally hormone dependent and aromatase inhibitors are used in routine practice before or after 1st line chemotherapy (CT) for HR positive patients. Deregulation of the Pi3K-Akt-mTOR signaling pathway is observed in many tumor types including endometroid carcinoma driven oncogenesis and hormonal resistance. Vistusertib (V) is a small-molecule ATP competitive inhibitor of both mTORC1 and mTORC2 complexes. Methods: Adult patients (pts) with recurrent oestrogen or progesterone (ER and/or PR) positive advanced/metastatic endometrial carcinoma, one previous line of chemotherapy (CT) allowed, with ECOG PS 0/1, were randomised (2:1, stratification according to prior CT line: 0 vs 1) to receive V (125 mg bid/2 days/week, orally) + Anastrozole (A, 1 mg/d, orally) or A alone. Treatments were given until progression, intolerable toxicity or patient willingness. Following a safety run in phase, a Simon’s 2-stage design was employed to explore the 8-week progression free rate (PFR-8W) according to central review (p1: 60%, p0: 40%, type I error rate of 5%, power of 80%). At the end of Stage II, if ≥24/46 evaluable pts are progression free at 8w in Arm A+V, the combination will be considered of interest for further investigation. Overall response rate (ORR) by RECIST v1.1, safety and progression-free survival (PFS) were key secondary endpoints. Results: Out of 75 patients (pts) enrolled, 73 were randomised and treated (Arm V+A: 49; Arm A: 24; median age: 69.5 y [36.8; 87.8]), BMI ≥30 kg/m²: 45%). PS ECOG was 0 (48%) and 44% of randomised pts were chemotherapy naïve; 12% previously received hormonal therapy. At the end of the safety run-in, no major safety concerns were reported. At the end of Simon’ Stage II, centrally assessed PFR-8W was 67.3% (33/49 [95% CI unilateral: 54.7; -]) for A + V arm and 39.1% (9/23 [[95% CI unilateral: 22.2; -[) for arm A. Median PFS was 5.2 months (95% CI: 3.4-8.9) and 1.9 months (95% CI: 1.6-8.9) for A+V and A arms, respectively. One complete response and 11 partial responses (PR) were observed (ORR: 24.5 % (CI 95% [13.3 – 38/9%]) in the combination arm and 4 PR in arm A (ORR: 17.4% [CI 95%: 5-38.8%]). Fatigue, lymphopenia, hyperglycaemia and diarrhoea were the main (≥10%) Grade ≥2 adverse events related to V. Overall survival and translational research are ongoing. Conclusions: The A+V combination demonstrated clinically and meaningful improvement in 8w-PFR and median PFS with manageable toxicity. PI3K pathway remains a key target for new therapies in endometrial cancer and translational research must help to better select pts benefiting from these targeted therapies. Clinical trial information: NCT02730923.

Resume Objectif Depuis les dernieres recommandations nationales elaborees par l’Institut national du cancer (INCa) et la Societe francaise de senologie et de pathologie mammaire (SFSPM) sur l’ensemble de la prise en charge diagnostique et therapeutique des carcinomes canalaires in situ (CCIS), de nouvelles publications ont fait emerger des interrogations en termes de bonnes pratiques et sur les possibilites de desescalade therapeutique dans la prise en charge des CCIS. L’actualisation de ces recommandations intervient dans un contexte de questionnement sur le surdiagnostic et son corollaire le surtraitement. Elle met a la disposition des professionnels des informations sur les bonnes pratiques correspondant a l’etat le plus recent des connaissances scientifiques et etudie notamment les possibilites de desescalade therapeutique. Methode Le processus d’elaboration est base sur une revue systematique de la litterature et sur le jugement argumente d’experts cliniciens au sein d’un groupe de travail multidisciplinaire. Avant publication, les recommandations sont revues par plus de cent experts cliniciens independants du groupe de travail. Resultats Cet article presente les recommandations nationales relatives a l’indication de l’IRM, la place de la macrobiopsie en cas de microcalcifications et la conduite a tenir en cas de CCIS de bas grade identifie par biopsie, dans le diagnostic des CCIS.

8 pages; International audience; Lateralization refers to the preferential use of one side of the body to perform certain tasks, often as a consequence of the specialization of cerebral hemispheres. Individuals may benefit from lateralization if it allows them to perform complex tasks simultaneously. Studies on laterality further suggest that sex and age can influence the extent of lateralization. However, most studies on lateralization have been performed on captive individuals, exposed to simplified environments and expressing limited behavioural repertoire. Here, we evaluated behavioural lateralization in the greater flamingo, Phoenicopterus roseus, through observations of wild individuals 5–37 years old. We examined the lateralization of simple behaviours (resting postures) and of several demanding behaviours requiring enhanced motor control and coordination (stamping for food and five courtship postures). Resting postures were not lateralized. In contrast, nearly all flamingos were completely lateralized for stamping, with a significant predominance of right-footed individuals. During courtship displays, twist-preens were significantly lateralized, yet with no dominant laterality at the population level. Finally, we detected a slight positive effect of age on the intensity of twist-preen lateralization, which may be related to the increased complexity of courtship displays with age in this species. Our results support the hypothesis that lateralization manifests in complex behaviours, even in wild animals.

Background In patients treated with cardiotoxic chemotherapies, the presence of cardiovascular risk factors and previous cardiac disease have been strongly correlated to the onset of cardiotoxicity. The influence of overweight and obesity as risk factors in the development of treatment-related cardiotoxicity in breast cancer (BC) was recently suggested. However, due to meta-analysis design, it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline (antineoplastic antibiotic) and trastuzumab (monoclonal antibody) cardiotoxicity. Methods and findings Using prospective data collected from 2012–2014 in the French national multicenter prospective CANTO (CANcer TOxicities) study of 26 French cancer centers, we aimed to examine the association of body mass index (BMI) and cardiotoxicity (defined as a reduction in left ventricular ejection fraction [LVEF] > 10 percentage points from baseline to LVEF < 50%). In total, 929 patients with stage I–III BC (mean age 52 ± 11 years, mean BMI 25.6 ± 5.1 kg/m2, 42% with 1 or more cardiovascular risk factors) treated with anthracycline (86% epirubicin, 7% doxorubicin) and/or trastuzumab (36%), with LVEF measurement at baseline and at least 1 assessment post-chemotherapy were eligible in this interim analysis. We analyzed associations between BMI and cardiotoxicity using multivariate logistic regression. At baseline, nearly 50% of the study population was overweight or obese. During a mean follow-up of 22 ± 2 months following treatment completion, cardiotoxicity occurred in 29 patients (3.2%). The obese group was more prone to cardiotoxicity than the normal-weight group (9/171 versus 8/466; p = 0.01). In multivariate analysis, obesity (odds ratio [OR] 3.02; 95% CI 1.10–8.25; p = 0.03) and administration of trastuzumab (OR 12.12; 95% CI 3.6–40.4; p < 0.001) were independently associated with cardiotoxicity. Selection bias and relatively short follow-up are potential limitations of this national multicenter observational cohort. Conclusions In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498). Trial registration ClinicalTrials.gov NCT01993498., Charles Guenancia and colleagues investigate the association of obesity to breast cancer treatment related cardiotoxicity., Author summary Why was this study done? Anthracyclines remain a cornerstone of breast cancer therapy, in combination with new-generation targeted drugs such as trastuzumab, and represent the major culprit in chemotherapy-induced heart disease. In a recent meta-analysis, we showed that overweight and obesity increased cardiotoxicity, but it was not possible to take into account associated cardiac risk factors or other classic risk factors for anthracycline and trastuzumab cardiotoxicity. We examined the association of body mass index (BMI) and cardiotoxicity using prospective data collected in the CANTO study, a French national cohort. What did the researchers do and find? In patients treated for stage I–III breast cancer with anthracyclines and/or trastuzumab, being obese was associated with increased risk of developing cardiotoxicity, regardless of other predictors of cardiotoxicity. Among all the classic risk factors for cardiotoxicity, overweight and obesity were by far the most common risk factors in this breast cancer population. What do these findings mean? Obesity appears to be a risk factor for cardiotoxicity in breast cancer patients. Overweight and obese patients may benefit from careful cardiac screening and follow-up during and after chemotherapy.

Background In this study we aimed to examine the independent effect of baseline QoL and persistent CRT among pts with early BC. Methods We included data stage I-III BC pts treated with chemotherapy who were included in the CANTO prospective cohort study (NCT-01993498) from 03/2012 to 12/2014. The primary outcome was CRT defined as the presence at 3-6 months after the end of treatment, of any of the following toxicities (NCI-CTC-AE): infection, venous or arterial thrombosis, neurological G2-4, digestive G3-4 or pulmonary toxicities G3-4). Treatment deliver including chemotherapy dose reductions were also examined. The independent variable of this study was baseline Qol defined by the EORTC QLQ-C30 subscales of general global health status (GHS) ( Results Among 3079 BC pts included in this analysis, 33% received neoadjuvant and 77% adjuvant treatment. Median age at diagnosis was 53 years, median BMI= 25 kg/m2, 94% of patients had a PS = 0 and 83% stage I-II disease. Pts reported on average a good GHS = 68 (±19) and PF = 90 (±14). GHS and PF were higher in women with better performance status PS = 0 vs 1+, (68 vs 60 p Conclusions Global and physical QoL before BC treatments are independently associated with CRT. QoL should be assessed before any treatment to identify patients at risk CRT. Clinical trial identification NCT01993498. Legal entity responsible for the study UNICANCER/Villejuif, France, 94805 Principal Investigator: Fabrice Andre Gustave Roussy – Villejuif. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

512 Background: We recently witnessed a trend to de-escalate CT and escalate ET in adjuvant BC treatment (tx). However, there has been limited prior research investigating the differential impact on QoL of tx classes. We aimed to test the impact of CT and ET on QoL PROs 2 yrs after diagnosis (dx). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of stage I-III BC pts that characterizes long-term toxicities of BC tx. For this analysis we included 4262 pts recruited from 2012-14. QoL was extensively evaluated using the EORTC QLQ C30 and BR23. Linear regression modeling was performed, adjusting for demographic and clinical factors, with use of CT and/or ET as independent variables. Analyses were stratified by menopausal status due to different tx patterns and sequelae of CT. Results: Median age at dx was 56 yrs, 63% of pts were post (PostM) and 37% premenopausal (PreM), 80% had Charlson score 0, 91% stage I-II. 26% received mastectomy, 52% CT (preM 68%, postM 44%; 86% anthracycline+taxane) and 82% ET (preM 89% tamoxifen; postM 88% aromatase inhibitor). 32% preM pts had menses 1 year after ET initiation. Overall, QoL deteriorates 2 yrs after dx. ET negatively impacts more QoL domains than CT at 2 yrs. Also, young age, smoking, income, aggressive local tx and physiological distress are often associated with low QoL. In the stratified analyses, in postM pts, mostly ET (not CT) is associated with deteriorated QoL. In contrast, in preM pts, mostly CT (not ET) is associated with deteriorated QoL. Table shows eg of associations. Conclusions: In a large prospective cohort of BC survivors, detrimental QoL 2 yrs after dx is mostly associated with ET; however, negative effects of CT persist on preM. This differential effect on QOL should be considered when choosing optimal adjuvant therapy and appropriate selection of pts for ET escalation should be a research priority. [Table: see text]

1043 Background: For ER+/HER2- metastatic breast cancer (mBC), efficacy of endocrine therapy + chemotherapy combination remain an open question. We hypothesized that continuing ER targeted therapy after progression in combination with chemotherapy may improve disease control. The objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy,oral vinorelbine, 50mg/3 time a week (OV) for AI pre-treated, ER+/HER2- mBC patients. Methods: Eligible patients had to have progressed on endocrine therapy and one or two lines of chemotherapy. They were randomized between vinorelbine (OV) and vinorelbine + AI (OV+AI). Primary end point was progression-free survival (PFS). To show an increase of median PFS (from 3.5 to 5.5 month, HR 0.636), with alpha = 5% and power = 80%, 130 evaluable patients were needed. Results: 121 patients were Included (OV = 61; OV+AI = 60). Median age was 68 (range: 49-87), Median time from metastatic diagnosis was 3.2 years (range 0 - 16.9). 109 patients (90%) had visceral metastases. They all had previously received an AI and had been treated with one line (N = 66, 54.5%), or 2 lines (N = 55, 45.5%) of chemotherapy. Median PFS was increased from 2.3 months with OV to 3.7 months with OV+AI, but this difference was not significant (HR 0.73 [95 % CI 0.50-1.06], log-rank test: P = 0.09) 81 patients (67%) had at least one adverse event (AE) of grade ≥ 3 (40 (66%) for OV vs 41 (68%) for OV+AI). The most common grade ≥ 3 AE were: GT gammas (23%), neutropenia (18%), arterial hypertension and lymphopenia (17%). The occurrence of 3 toxic deaths (OV = 1; OV+AI = 2) secondary to febrile aplasia motivated the early cessation of this clinical trial. 9 patients (5 OV (10%) and 4 OV+AI (8%) presented an objective complete or partial response. Conclusions: The addition of AI to OV over OV alone in AI resistant mBC was associated with a non-significant improvement of PFS, but both PFS are lower than expected. Metronomic OV schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open. Clinical trial information: EudraCT Number: 2015-000401-39.

A 35-year-old man had prolonged occupational exposure to lead carboxylate, triethylbenzene, xylene, and dichloromethane, when he developed a subacute predominantly sensory neuropathy. Ultrastructural examination of a peripheral nerve biopsy showed axonal degeneration and unusual lesions of the myelin, with Schwann cell sequestration of vesicular and lamellar debris. Biochemical analysis of lead in a frozen peripheral nerve specimen revealed no significant difference between the propositus and a control. The authors were unable to find any similar peripheral nerve lesions in the literature dealing with neurotoxic chemicals. Any of the several organic solvents could have equally caused the neuropathy and may have been potentialized by the other chemicals.