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Objective Cognitive complaints are more frequent in women with breast cancer (BC) than in healthy controls and can be present before any treatment. Findings regarding contributive factors remain inconsistent. This study aimed to identify different groups of patients with cognitive complaints at BC diagnosis and to determine whether these different groups were associated with demographic, medical, or psychological characteristics. Methods Cognitive complaints were assessed in a subset of 264 women from the French multicenter prospective CANTO cohort, at baseline before any treatment. Clustering analyzes were performed using the six-cognitive dimension Costa's scoring of the FACT-Cog V3. Univariable analyses were used to study how cognitive function (standardized neuropsychological tests, ICCTF), anxiety, depression, fatigue, and quality of life (HADS, FA12, QLQ-C30) were associated with specific cognitive complaints groups. Results Results included 263 women (54±11 years), newly diagnosed with BC (69% stages I-III). Four distinct groups emerged, ranged from "no complaints" (22.8%), "low complaints" (55.1), "mixed complaints" (14.5%), to "consistent complaints" (7.6%). No significant differences were found in terms of demographic and medical factors between the four groups. However, the groups with higher proportions of patients with complaints were found to have more impairment in executive function, higher scores of anxiety, depressive symptoms, and fatigue, and lower quality of life, than the groups with lower proportions of cognitive complaints. Conclusion Using complete cognitive assessment prior to BC treatment, we identified four distinct cognitive complaints groups with specific characteristics. This work provides valuable clinical basis to further investigations for a better understanding of cognitive complaints and their associates.

221 Background: Optimal comprehensive survivorship care, beyond screening of recurrences and new cancers, and including health promotion, management of physical as well as psychosocial needs and chronic conditions is insufficiently delivered. To increase patient (pt) empowerment and maximize the uptake of multidisciplinary strategies serving all survivorship needs, we implemented a proactive survivorship care pathway offered for pts with early BC at the end of their primary treatment phase (surgery, chemotherapy, radiotherapy). Methods: The pathway consisted of the following components: 1) receipt of a personalized survivorship care plan (SCP), 2) invitation to attend face-to-face group seminars focused on specific themes and a comprehensive survivorship consultation for multidisciplinary referrals (”the transition day”) 3) access to a mobile application (app) delivering personalized education according to symptoms reported and 4) decision aids for helping physicians to manage prevalent symptoms and side effects related to BC treatment. Administrative data were collected. A pre-specified post-experience survey was sent to all pts four weeks post pathway delivery to inform program implementation with a minimum requirement of 50 responses. BC physicians and members of the multidisciplinary implementation team (MIT) answered a dedicated survey. For the overall pathway and each of its components we descriptively evaluated the following domains: satisfaction (primary outcome), uptake, perceived usefulness, barriers for delivery, and suggestions for improvement. A 70% satisfaction rate would define a positive experience. Results: From October 2021 to April 2022, 241 SCP were delivered, and 98 pts attended the “transition day”. 62 pts replied to the survey, 42 (67%) had received the SCP, 34 (55%) attended the “transition day”, 36 (57%) accessed the app. Only 21 pts (34%) who answered the survey received the full pathway, 81% of whom were very or completely satisfied with it. Perceived usefulness of individual components and for pts that received the full pathway were, respectively: 64% and 90% for the SCP, 91% and 95% for the “transition day”, 72% and 90% for the app. Among 14 BC physicians, agreement regarding the usefulness of the components was: 93% for the SCP, 86% for the decision aids, 93% for the “transition day”, and 86% for the app. The MIT (n = 13) reported high engagement and satisfaction (100%). Main actionable points for improvement included: automated screening and SCP preparation, virtual “transition day”, increase physicians’ awareness. Conclusions: In this pilot phase, pts were satisfied with receiving a proactive survivorship care pathway and the majority reported that the components were useful for supporting their needs. This study informed improvements on program penetration. Evolution towards sustainability phase is ongoing including dissemination to other cancers and centers.

INTRODUCTION: Fatigue is a frequent and disturbing symptom in oncology but remains undertreated. Given the absence of effective drug treatment, non-pharmacological interventions have a prominent place in the treatment of fatigue. However, they are relatively unknown by professionals who lack of clear points of reference to refer patients with confidence. This article aims to improve the knowledge about this therapeutic field through an updated synthesis of the levels of recommendations and available evidence. METHODS: A three-step approach was conducted, including (1) a synthesis of international guidelines on non-pharmacological interventions in the treatment of fatigue among adults in oncology, (2) a systematic review of recent data in the literature, (3) a comparison between the synthesis of guidelines and the systematic review with the aim of updating the levels of evidence. RESULTS: Five guidelines were synthesized; 111 systematic reviews were analyzed. Their comparison mainly showed: (1) a convergence in favor of the use of physical activity, educational interventions and cognitive-behavioral therapies, with levels of evidence ranging from moderate to high; (2) a consolidation of short-term efficacy evidence to support the use of mindfulness-based approaches and yoga; 3) the persistence of a lack of sufficiently reliable data to establish the efficacy of other types of intervention. DISCUSSION: Supported by international guidelines and recent data, the use of non-pharmacological interventions in the treatment of fatigue is critical and has to become better known.; INTRODUCTION: Malgré sa fréquence et sa pénibilité, la fatigue reste insuffisamment prise en charge en oncologie. En l’absence de traitement médicamenteux efficace, les interventions non pharmacologiques occupent une place thérapeutique essentielle. Elles sont toutefois mal connues des professionnels qui manquent de repères pour orienter en confiance les patients. L’article vise à un meilleur repérage dans ce domaine à travers une synthèse actualisée des niveaux de recommandations et de preuves disponibles. MÉTHODES: Une démarche en trois étapes a été adoptée, comprenant (1) une synthèse des référentiels internationaux portant sur les interventions non pharmacologiques dans le traitement de la fatigue en oncologie adulte, (2) une revue systématique des données récentes de la littérature, (3) une comparaison entre synthèse des référentiels et revue de la littérature à visée d’actualisation des niveaux de preuve. RÉSULTATS: Cinq référentiels ont été synthétisés, 111 revues systématiques ont été analysées. Leur comparaison a principalement montré : (1) une convergence en faveur du recours à l’activité physique, aux interventions éducatives et aux thérapies cognitivo-comportementales, avec des niveaux de preuves allant de modérés à élevés ; (2) une consolidation des données d’efficacité à court terme pour les approches basées sur la pleine conscience et le yoga ; (3) la persistance d’une absence de données suffisamment fiables pour établir l’efficacité des autres formes d’intervention. DISCUSSION: Soutenu par les référentiels internationaux et les données récentes de la littérature, le recours aux interventions non pharmacologiques dans le traitement de la fatigue est un incontournable qu’il reste à faire mieux connaître.

Background Physical activity has shown beneficial effects in the treatment of breast cancer fatigue; nevertheless, a significant portion of patients remain insufficiently physically active after breast cancer. Currently most patients have a smartphone, and therefore mobile health (mHealth) holds the promise of promoting health behavior uptake for many of them. Objective In this study, we explored representations, levers, and barriers to physical activity and mHealth interventions among inactive breast cancer patients with fatigue. Methods This was an exploratory, qualitative study including breast cancer patients from a French cancer center. A total of 4 focus groups were conducted with 9 patients; 2 independent groups of patients (groups A and B) were interviewed at 2 consecutive times (sessions 1 to 4), before and after their participation in a 2-week mHealth group experience consisting of (1) a competitive virtual exercise group activity (a fictitious world tour), (2) participation in a daily chat network, and (3) access to physical activity information and world tour classification feedback. We used a thematic content analysis. Results Several physical activity levers emerged including (1) physical factors such as perception of physical benefit and previous practice, (2) psychological factors such as motivation increased by provider recommendations, (3) social factors such as group practice, and (4) organizational factors including preplanning physical activity sessions. The main barriers to physical activity identified included late effects of cancer treatment, lack of motivation, and lack of time. The lack of familiarity with connected devices was perceived as the main barrier to the use of mHealth as a means to promote physical activity. The tested mHealth group challenge was associated with several positive representations including well-being and good habit promotion and being a motivational catalyzer. Following feedback, modifications were implemented into the mHealth challenge. Conclusions mHealth-based, easily accessed group challenges were perceived as levers for the practice of physical activity in this population. mHealth-based group challenges should be explored as options to promote physical activity in a population with fatigue after breast cancer.

PURPOSE Adverse effects of breast cancer treatment can negatively affect survivors’ work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not prospectively assess the combined impact of treatment and related sequelae on employment. METHODS We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events [CTCAE] v4) and PROs (European Organization for Research and Treatment of Cancer [EORTC] Quality of life Questionnaires, Breast cancer module [QLQ-BR23] and Fatigue module [QLQ-FA12], Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates. RESULTS Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio [OR] v chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR v no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR v no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR v no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR v no, 2.29; 95% CI, 1.34 to 3.91). CONCLUSION Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.

12022 Background: CRF is among the most common and troublesome symptoms experienced by BCS. While preventing severe post-tx CRF is a major survivorship need, limited tools exist to predict this risk. We aimed to describe the long-term prevalence rates and to identify BCS that are more likely to develop severe CRF. Methods: CANTO is a multicenter, prospective clinical study of stage I-III BCS (NCT01993498). Longitudinal data were collected at diagnosis (dx), 0.5 (T1), 1 (T2) and 3 (T3) years post-tx. The primary outcome of interest was severe post-tx global CRF (score ≥ 40/100, EORTC QLQ-C30). Secondary outcomes were physical, emotional and cognitive dimensions of CRF (QLQ-FA12). Multivariable logistic regression models retained associations with severe CRF by bootstrapped Augmented Backwards Elimination, validated using 10-fold internal cross-validation and overoptimism-corrected AUC. Results: Among 6619 BCS, mean age at dx was 56.5 years (SD 11.5), mean BMI was 25.9 Kg/m2 (SD 5.4), 53.3% and 80.8% received chemotherapy (CT) and hormonotherapy (HT), respectively. Prevalence rates of severe global CRF were 25.0% (dx), 35.6% (T1), 34.0% (T2) and 31.6% (T3). Severe post-tx global CRF was consistently associated with higher BMI, worse insomnia and pain, and severe pre-tx CRF. Receipt of CT increased odds of severe CRF at T1, whereas associations of HT with CRF emerged at T2 and T3 (Table). The estimated risk of severe CRF at T3 was 14% for a BCS with BMI 23.0 Kg/m2 and no concomitant symptoms at dx, whereas it was 82% for a BCS with BMI 32.0 Kg/m2, severe insomnia, pain and pre-tx CRF, receiving HT. Anxiety and depression at dx were consistently retained in models of severe post-tx emotional and cognitive CRF (all p

International audience; BackgroundMany breast cancer (BC) survivors are employed at diagnosis and are expected to return to work after treatment. Among them, around 50% are overweight or obese. There are limited data about the impact of body weight on their ability to return to work.MethodsWe used data from CANcer TOxicity (NCT01993498), a prospective, multicentre cohort of women with stage I–III BC. Professionally active women who were ≥5 years younger than retirement age were identified. Multivariable logistic regression models examined associations of body mass index (BMI) at diagnosis and subsequent weight changes with non-return to work 2 years after diagnosis, adjusting for psychosocial, treatment and behavioural characteristics.ResultsAmong 1869 women, 689 were overweight or obese. Overall, 398 patients (21.3%) had not returned to work 2 years after diagnosis. Non-return to work was more likely for overweight or obese than underweight or normal weight patients (adjusted OR (aOR) 1.32; 95% CI, 1.01 to 1.75; p=0.045). Weight loss (≥5%) was observed in 15.7% overweight or obese and 8.7% underweight or normal weight patients and was associated with significant increases in physical activity only among overweight or obese patients (mean change, +4.7 metabolic-equivalent-of-task-hour/week; 95% CI +1.9 to +7.5). Overweight or obese patients who lost weight were more likely to return to work compared with those who did not lose weight (aOR of non-return-to-work, 0.48; 95% CI 0.24 to 0.97, p=0.0418), whereas weight loss was associated with increased odds of non-return to work among underweight or normal weight women (aOR 2.07; 95% CI 1.20 to 3.56, p=0.0086) (pinteractionBMI×weight changes=0.0002). The continuous trend of weight gain on non-return to work was significant for overweight or obese patients (aOR for one-percent-unit difference, 1.03; 95% CI 1.01 to 1.06, p=0.030).ConclusionsExcess weight may be a barrier to return to work. Among overweight or obese BC survivors, weight loss was associated with higher rates of return to work, whereas further weight gain was associated with lower likelihood of return to work. Employment outcomes should be evaluated in randomised studies of weight management.

Background: More than two decades ago several trials have shown equivalent survival between breast conserving surgery (BCS) and MAST. Among a contemporary cohort of patients (pts) with Stage I BC who would be expected to be candidates for BCS; we examined the initial choice of surgery and factors associated with it. Pts and methods: Prospective cohort study including pts with clinical Stage I BC treated at a National Comprehensive Cancer Network center that participated in the BC outcomes database from 2000-09. Descriptive analyses were performed examining the proportion of pts who initially underwent MAST vs BCS. Factors associated with initial surgery were analyzed using multivariable logistic regression. Results: Of 10,249 pts with clinical Stage I BC, 2,361(23%) underwent MAST as the initial surgery and 7,888 (77%) BCS. Of those, 8% were ultimately converted to MAST. The median time from diagnosis to initial surgery was longer among the MAST group (4 vs. 6 weeks). Patient, tumor, care and institutional factors were associated with higher rates of initial MAST: 30% of pts with 30 kg/m2 (obese). There was significant institutional variation, with rates of initial MAST ranging from 14-30%. The use of preoperative magnetic resonance imaging (MRI) was associated with a higher rate of initial MAST (32% vs.22%). Differences by tumor subtype were observed, 38% of pts with HER2+/HR- tumors had initial MAST vs. 22-28% among other subtypes. In the multivariate model, age, BMI, comorbidity, income, center, stage, tumor subtype, grade, histology and preoperative MRI were associated with the choice of initial surgery. Multivariate logistic model to investigate factors associated with initial MAST MAST vs BCS OR95%CIPAge Conclusions: Among a cohort of pts with small node negative BC, 23% elected to have MAST with significant variation associated with choice of treatment, while some of this variation is likely appropriate and clinically indicated, further studies to assess pt understanding of the tradeoffs between BCS and MAST is warranted. These findings need to be considered in light of the increasing number of pts who are choosing MAST/bilateral MAST. Citation Format: Ines Vaz Luis, Melissa E Hughes, Angel Cronin, Hope S Rugo, Stephen B Edge, Beverly Moy, Richard Theriault, Michael J Hassett, Eric P Winer, Nancy U Lin. Variation in the use of mastectomy (MAST) in women with small node negative breast cancer (BC) treated at US academic institutions [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-03.

561 Background: Cognitive impairment has been reported among breast cancer (BC) patients (pts) after adjuvant chemotherapy. However, very few studies focused on cognitive function at diagnosis. Here we aimed to describe cognitive impairment among recently diagnosed BC before any treatment. Methods: A predefined sub-study of the French national prospective cohort of cancer and toxicities performed extensive objective and subjective cognitive assessment before any BC treatment (surgery or neo-adjuvant treatment). This study included a group of pts with newly diagnosed invasive Stage I-III BC and a group of healthy control (HC) women matched on age and education level. Episodic and working memory, executive functions, processing speed, attention, cognitive complaints (FACT-COG), anxiety and depression (HADS) and fatigue dimensions (FA12) were assessed with neuropsychological tests and the referred self-report questionnaires. Objective and cognitive impairment were defined according to International Cognition and Cancer Task Force recommendations. Results: 264 women (median age 54±11 years) recently diagnosed (average of 37 days after initial diagnosis) with invasive BC (stage I-II, 69%) and 132 matched HC participated in this study. Impaired working memory (20% vs 4%), information processing speed (36% vs 17%), attention (16% vs 1%) and executive function (21% vs 8%) were higher among pts than in HC (p < 0.001). In addition, 24% (n = 64) of pts reported cognitive complaints versus 12% of HC (n = 16, p < 0.01). Emotional and cognitive fatigue were higher in pts than HC (mean 24 vs 15 and 18 vs 11, p < 0.01). Similarly, higher levels of anxiety and depression were observed in patients when compared with HC (respectively in 41% and 3% of patients vs 10 and 1% for HC, p < 0.001). Objective cognitive impairment was not associated with cognitive complains. Both objective and subjective cognitive impairment were not associated with anxiety or depression. However cognitive complain was associated with fatigue (p < 0.001). Conclusions: In this large study, compared to HC, patients recently diagnosed with a localized BC reported more cognitive complains and objective cognitive impairment before surgery, without link with emotional status, but with fatigue. Further understanding of the biology and correlates of cognitive dysfunction at BC diagnosis is needed (CANTO-NCT01993498).

538 Background: Endocrine therapy resistance is a major cause of distant recurrence (DR) in HR+ breast cancer. Currently, no data exists evaluating differences in clinical behavior after DR between patients (pts) treated in the adjuvant setting with different endocrine therapy regimens. The aim of this study was to analyze post-DR survival of pts treated on BIG 1-98. Methods: BIG 1-98 compared 5 years of adjuvant treatment between 4 arms: tamoxifen (T), letrozole (L), T followed by L (TL) and L followed by T (LT). After 8.1 years median follow-up (follow-up through 2010), 911 (T n = 302, L n = 285, TL n = 170, LT n = 154) of 8010 pts had DR as site of first recurrence. Univariate and multivariable Cox analyses were performed to determine features associated with post-DR survival. With 661 total observed deaths, statistical power was 0.8 to detect a hazard ratio (HaR) > 1.24 at the 2-sided 0.05 level of significance. Results: Median follow up time after DR was 59 months (IQR: 29-88). Among all pts with DR, 38.1% were ≥ 65 years at study enrollment, 61.9% had tumor size > 2 cm, 69.7% were node positive. Neo/adjuvant chemotherapy was administered to 35.6% of pts. There was no difference in post-DR survival by treatment arm (median survival: T 20.8, L 17.9, TL 17.3, LT 20.8 months; p = 0.21). In multivariable analysis, older pts (HaR 1.36; p = 0.0002), tumors > 2cm (HaR 1.2; p = 0.04), ≥ 4 positive nodes (HaR 1.32; p = 0.05) and PR- tumors (HaR 1.28; p = 0.001) had significantly worse post-DR survival. Endocrine treatment arm, type of surgery, radiotherapy and neo/adjuvant chemotherapy were not associated with post-DR survival in the multivariate model. Conclusions: Treatment with adjuvant T, L or their sequence were not associated with differences in survival after DR. We observed significant differences in survival by primary tumor size, nodal and PR status, which suggest that traditional high-risk features remain prognostic in the metastatic setting. Clinical trial information: NCT00004205.

11566 Background: CANTO (CANcer TOxicities - NCT01993498) is a French multicenter prospective longitudinal study dedicated to the quantification and characterization of side effects after treatment for patients with stage I-III breast cancer, and to the development of predictors of toxicities. Methods: The CANTO study has included > 12,000 patients, assessed at diagnosis, and 3-6 months (T0), 15 months (T12), and year 3 and 5 after treatment completion. In the current report, we focus on key toxicities at T0 and T12 according to chemotherapy (CT) administration. For each side effect, 4 populations were defined according to its occurrence at T0 and/or T12 (no/no, no/yes, yes/no, yes/yes). Results: We analyzed 4684 patients with T0 and T12 consolidated data. Median age at diagnosis was 57y (22-89). Patients (pts) had HR+/HER2-, HER2+ or triple negative tumors in 78.9%, 12.4% and 8.7% of cases, respectively. Overall, 2516 pts (53.7%) received CT. Most CT pts (81%) received a sequential anthracyclines– taxanes schedule. As an example, a high proportion of patients presented neurological symptoms including cognitive symptoms, sensory or motor neuropathy, paresthesia, headache, etc (all grades) at either T0 or T12. Overall, CT was strongly associated with neurotoxicity at all times (OR = 2.27, p < 0.0001). However, proportions of patients with neurological side effects changed between T0 and T12. The table shows the proportions of the 4 categories of pts in the CT and no CT groups. Furthermore, at T12, neurological symptoms remained more frequent in the CT group, whether pts had symptoms at T0 (CT vs no CT, 81% vs 77%, p = 0.007) or not (CT vs no CT, 41% vs 36%, p = 0.03). Similar temporal trends were observed (with specific percentages for each considered side effect) for detailed neurological toxicities, pain and joint/bone toxicity (stratified on endocrine therapy), gastro-intestinal, pulmonary and cardiac toxicities. Conclusions: Overall, symptoms burden is extremely high at T0 and T12 after treatment, and much higher in pts receiving CT. A high temporal variability was observed in all subsets, including a clinically meaningful delayed onset of e.g. neurological side effects. Clinical trial information: NCT01993498. [Table: see text]

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]

11515 Background: Many BC survivors report fatigue. The relevant genomic correlates of fatigue after BC are not well understood. We applied a previously validated machine learning methodology (Oh 2017) to GWAS data to identify biological correlates of fatigue induced after tx. Methods: We analyzed 3825 BC pts with GWAS data (Illumina InfiniumExome24 v 1.1) from the CANTO study (NCT01993498). The outcome of this study was post-tx fatigue 1 year after the end of primary chemotherapy/radiotherapy/surgery using the EORTC C30 fatigue subscale (overall fatigue) and the EORTC FA 12 fatigue domains (physical/emotional/cognitive). For each domain, we limited the study group to those with zero baseline fatigue and defined severe fatigue change as score increase above the third quartile. We tested univariate correlations between severe fatigue in each domain and 496539 SNPs as well as relevant clinical variables. The machine learning prediction model based on preconditioning random forest regression (PRFR) (Oh et al., 2017), was then built using the SNPs with ancestry adjusted univariate p-value < 0.001 and clinical variables with Bonferroni adjusted p-value < 0.05. The model was validated in a holdout subset of the cohort. Gene set enrichment analysis (GSEA) was performed using MetaCore to identify key biological correlates relevant to tx-induced fatigue. Results: Distinct results were found by fatigue domain (table). GSEA showed that the cognitive fatigue model SNPs included biomarkers for cognitive disorders (p = 1.6 x 10-12) and glutamatergic synaptic transmission (p = 1.6 x 10-8). Conclusions: A SNP based model had differential performance by fatigue domain, with a potential genetic role on risk and biology for tx induced cognitive fatigue. Further research to explore biomarkers of tx induced fatigue are needed. [Table: see text]

11564 Background: The interplay between breast cancer (BC) late effects, psychosocial and work-related factors in return to work (RTW) is not well understood. Previous reports were retrospective and did not combine all these features. Methods: We used data of a French prospective cohort study (CANTO, NCT01993498) of stage I-III BC patients (pts) including detailed clinical data of 1,874 pts working at diagnosis (dx) and ≥5 years younger than legal retirement age. The outcome was non-RTW 2 years after dx. Multivariable regressions were conducted to identify correlates of non-RTW. First, we examined the independent effect of treatments, toxicities (Common Toxicity Criteria Adverse Events), and patient reported outcomes (EORTC BR23 and FA12; Hospital Anxiety and Depression Scale) collected shortly after end of primary treatment. Then, in a restricted sample of 1,003 pts with working conditions (WC) information available, we fitted models to account for detailed pre-dx WC including type of contract, working hours, strenuous postures, supportive environment, degree of autonomy and perception of work. All models were adjusted for age, stage, marital status, socioeconomic status and comorbidities. Results: Two years after dx, 21% of pts did not work. Adjusted odds of non-RTW were increased among pts treated with combinations of chemotherapy (CT) and trastuzumab (TR) (e.g. OR of CT-TR = 2.20 [95% CI 1.24-3.88] and OR of CT-TR-hormonotherapy (HT) = 1.72 [1.13-2.63] vs. treated only with CT-HT), who had severe arm morbidity (OR = 1.73 [1.27-2.36] vs. no), severe emotional fatigue (OR = 1.55 [1.03-2.32] vs. no), anxiety (OR = 1.51 [1.02-2.23] vs. no), or depression (OR = 2.23 [1.27-3.94] vs no). In addition, we also found that the odds of non-RTW were increased among pts who had shift working hours (OR = 2.23 [1.32-3.76] vs. no), who did not work in a supportive environment before dx (OR = 2.24 [1.44-3.50] vs. supportive) and who perceived their job as boring (OR = 3.57 [1.71-7.46] vs. not boring). Conclusions: More than 1/5 of pts did not RTW 2 years after dx, with treatment (trastuzumab), clinical, psychological and work-related factors being associated with job reintegration. Multidisciplinary strategies are needed to support BC survivors.

1004 Background: Studies of checkpoint inhibitor monotherapy show only modest activity in HR+ MBC. We report data from the first randomized study comparing E plus P versus E alone in HR+/HER2- MBC. Methods: Eligible patients (pts) had HR+/HER2- MBC, ≥2 lines of hormonal therapies and 0-2 lines of chemotherapy for MBC. Pts were randomized 1:1 to E 1.4mg/m2 intravenously (IV) on d1 and d8 with P 200 mg/m2 IV on d1 of a 21-day cycle (Arm A) or E alone (Arm B). At time of progression, pts in arm B could crossover and receive P alone. Primary endpoint was progression-free survival (PFS). Key secondary endpoints were: objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), neutrophil-lymphocyte ratio (NLR), tumor mutation burden (TMB), and genomic alterations by next generation sequencing on archival tissue. Results: 88 pts initiated protocol therapy; the median age was 58, median prior lines of chemotherapy 1, prior lines of hormonal therapy 2. Median follow-up was 6.3 months. Median PFS and ORR were not different between Arms A and B (PFS 4.1 vs 4.2 months p = 0.38; ORR 25% and 34% respectively (p = 0.49). 14 patients initiated crossover treatment with pembrolizumab; 1 patient experienced a PR (ORR 7%). All-cause AEs occurred in 100% of pts (G3-4, 54.6%) including 2 treatment related deaths on Arm A, both from known AEs attributed to both drugs. PD-L1 assay was performed in 65 pts: 24 (36.9%) had PD-L1 positive ( > 1% with 22C3, centrally tested) tumors. PD-L1 status, TILs, NLR, TMB, and genomic alterations were not associated with PFS (Table). Updated data, including OS and genomic results, will be presented. Conclusions: Among pts with HR+/HER2- MBC, the combination of E and P was not associated with longer PFS than E alone in the ITT or PD-L1+ population, though the PD-L1+ subgroup had very limited power to assess P benefit. Clinical trial information: NCT03051659. [Table: see text]

517 Background: Use of growth factors (GF) adds considerable expense and some toxicity to adjuvant breast cancer chemotherapy. We tested the feasibility and safety of omitting routine GF use during the T portion of DD AC-T. Methods: This is a prospective, single-arm study in which patients (pts) who completed 4 cycles of DD-AC proceeded to DD-T 175 mg/m2 every two weeks (wks) without routine GF (NCT02698891). Key inclusion: age≤ 65, ECOG PS≤1, absolute neutrophil count (ANC) ≥1500/mm3, and no febrile neutropenia (FN) during DD-AC. Criteria to treat for T included ANC ≥1000/mm3. Peg-F was given only if pts had FN in a prior cycle, or at investigator discretion if infection or treatment delay > 1 wk. Once Peg-F was given, pts received it in all future cycles. The primary endpoint was the rate of T completion ≤ 7 wks from cycle 1 day 1 (C1D1) to C4D1. Secondary endpoints included total use of Peg-F, rates of hematologic toxicity and FN, reasons for dose modification or hold. If ≥85% of pts completed T on time, the regimen would be considered feasible. If the true on-time completion rate is 75%, the chance the regimen would be declared infeasible is 91%, and if it is 85% the chance that the regimen is falsely declared infeasible is 10% (power = 0.899). ≥100/125 pts had to complete T on time for the regimen to be deemed successful. Results: Among 127 pts enrolled, 125 received ≥1 dose of protocol therapy and are included in the analysis. Median age at registration was 46 (range 21-65). Median C1D1 ANC was 7500/mm3 (range 1500-20500). 112 (90%) (95% CI 83-94%) pts completed DD-T ≤ 7 wks, and 3 (2%) completed within > 7 wks (2 due to neutropenia); 10 (8%) did not complete all cycles of T. Omission of Peg-F was not causally related to non-completion of T in any pts. The most common reasons for dose reduction or delays were non-hematologic. One pt had FN but was able to complete T on time. Eight (6.4%) pts received Peg-F during the trial. Conclusions: Omission of routine GF use during DD-T according to a pre-specified algorithm appears safe, feasible, and was associated with a 95.7% reduction in use of Peg-F, relative to the current standard of care. Additional analyses including cost implications are ongoing. Clinical trial information: NCT02698891.

11562 Background: Overweight and obesity are strongly linked to poorer BC-specific outcomes, quality of life and financial burden in cancer care. Weight loss interventions have the potential to improve such outcomes. Fewer data exist on whether excess weight and post-diagnosis weight changes impact the ability of BC survivors to return to work (RTW). Methods: CANTO (NCT01993498) is a multicenter prospective longitudinal study of 12000 patients (pts) with stage I-III BC that characterizes long-term toxicities of BC treatment. Of 5801 pts enrolled from 2012-2014 (last data lock), we identified 1874 pts who were professionally active at BC diagnosis, ≥5 years (yrs) younger than minimum legal retirement age (62 yrs) and with updated work status 2 yrs after diagnosis. Logistic regression models evaluated the impact of body mass index (BMI) at diagnosis and of weight changes over 2 yrs after diagnosis on odds of non-RTW, adjusting for age, education, income, BC treatment and recreational physical activity (PA). Results: 37% pts were overweight or obese at diagnosis (BMI ≥25 kg/m2): 34% of them gained ≥5% and 16% lost ≥5% weight after diagnosis. Rates of non-RTW at 2 yrs were significantly higher in overweight or obese vs under or normal weight pts (27% vs 18%, p≤.001; adjusted odds ratio 1.37, 95% Confidence Interval [CI] 1.04-1.80, p = .017). Overweight and obese pts who did not RTW experienced higher increments in weight (mean [95% CI]: +3.6% [+2.3, +4.9] vs +1.5% [+0.8, +2.2]) and reported more modest changes in PA (mean [95% CI]: +1.0 [-1.4, +3.5] vs +2.1 [+0.8, +3.3] MET-h/week) vs those who did RTW. Weight changes independently impacted odds of non-RTW in overweight and obese pts (p for interaction weight change*BMI ≤.001): a 5% weight gain was associated with 17% increase in adjusted odds of non-RTW (95% CI 2-35%, p = .024), whereas a loss ≥5% with 60% reduced odds of non-RTW vs weight gain (95% CI 18-82%, p = .013). Conclusions: Excess weight and weight changes are significantly associated with occupational reintegration after BC in overweight and obese pts. Randomized studies testing dedicated weight control interventions should also measure outcomes of social rehabilitation in this large subset of survivors. Clinical trial information: NCT01993498.

10073Background: At time of BC diagnosis, a large proportion of patients (pts) work. However, long term effects of BC and BC treatment are likely to impact employment status in follow up. Methods: ...

TPS10125 Background: Corresponding with improved survival among breast cancer patients an awareness of the long term effects of cancer treatments has increased. There is now a call for better coordination of care and management of these patients to focus on their survivorship. This study will identify factors associated with the development and persistence of long term toxicities in patients treated for Stage I-III breast cancer. In addition, it will characterize their incidence as well as, psychological, social and economic impacts. Methods: This is a prospective cohort study enrolling newly diagnosed invasive cT0-cT3, cN0-3, M0 breast cancer patients of 26 French comprehensive cancer centers. All patients will be followed for a minimum of 5 years. Patients will be assessed at diagnosis, 3-6 (M0), 12 (M12), 36 (M36), 48 (M48), 60 (M60), months after treatment completion. Treatment completion is defined as completion of primary surgery, chemotherapy or radiotherapy, whichever comes last. Adjuvant trastuzumab, endocrine therapy or participation in clinical trials can be ongoing. CANTO collects an extensive list of clinical, treatment, and toxicity data including validated patient reported outcomes questionnaires ( Hospital Anxiety and Depression scale [HADS], Scheier et Carver’s Questionnaire, Life Orientation Test-Revised [LOT-R], Beck Depression Inventory [BDI-SF], European Organization for Research and Treatment-QOL questionnaire for breast cancer [EORTC QLQC30-BR23], EORTC-FA13, 12 Item Short Form Survey [SF12], Global physical activity questionnaire [GPAQ]6, impact of cancer questionnaire [IOCv2], economic and social questionnaires). Blood collection is available for all patients at diagnosis, M0, M12, M36 and M60. Genotyping will be performed in all samples. Biologic substudies are ongoing (e.g, microbiotic and cognitive substudy). CANTO aggregates a multidisciplinary team of French investigators and created a dedicated national network. Enrolment started in 2012 and by December 2016, 10030 patients were already enrolled, with a goal of 12.000 patients. Clinical trial information: NCT01993498.

1034 Background: As a single agent, eribulin is an active agent among MBC pts. In the first-line setting, pertuzumab improves progression free and overall survival when added to trastuzumab and chemotherapy (CT); however there are limited data in the second line or beyond. The primary aim of this study was to evaluate the activity of eribulin in combination with trastuzumab and pertuzumab in pts with HER2+ MBC whose cancers are refractory to trastuzumab containing regimens. Safety and toxicity were examined and correlative studies are also planned. Methods: Single center, single-arm, phase II, 2 cohorts study planned to enroll up to 81 pts. The studied combination would be of clinical interest if the true overall response rate (ORR) was 40% among those without prior pertuzumab exposure (Cohort A) and 30% among those with prior pertuzumab exposure (Cohort B). The trial was stopped prematurely due to low accrual. Prior to the start of the phase II study, a run-in established dose of eribulin with standard dose of trastuzumab and pertuzumab (1.4mg/m2 days 1, 8 /21 days). Results: Of 32 pts enrolled, 6 were in the run-in, 19 in Cohort A and 7 in Cohort B. Most pts were heavily pre-treated (median [range] lines of CT for metastatic disease, run-in: 4[2-11], cohort A: 2.5 [0-7], cohort B: 3[1-8]). In cohort A, 5 pts had partial responses (ORR = 26% [95% CI 9-51%]), 1 (5%) experienced stable disease (SD) lasting ≥ 6 months and 11 (58%) had a SD lasting < 6 months. In cohort B, the ORR was 0% [95% CI 0-41%]), 1(14%) experienced SD lasting ≥ 6 months and 5 (75%) had a SD lasting < 6 months. The combination was well tolerated, most adverse events (AE) were mild to moderate. Hematologic toxicity was the most frequent grade 3-4 AE. Analyses looking at tissue genomic markers and cell free DNA will be presented. Conclusions: We observed modest activity of the treatment combination in those without prior pertuzumab exposure but limited activity in unselected pts with HER2+ MBC. The study was limited by small sample size. Correlative studies may help us to understand resistance and response to eribulin with anti-HER2 therapy and the interplay between CT and targeted therapy. Clinical trial information: NCT01912963.

10069 Background: A substantial proportion of breast, colo-rectal and prostate cancer patients (pts) can expect long term disease free survival after their primary treatment. Among those, fatigue commonly persists after diagnosis (dx) and can be debilitating. In this study, we evaluated the incidence of fatigue 2 years (y) after cancer dx and its association with health behaviors. Methods: We used a French population based cross-sectional study, which included a representative sample of pts from 12 cancer types (VICAN2). VICAN2 surveyed 4347 pts 2 y after dx. There is a 99% completion rate of fatigue related questions. For this study, we included 2017 pts with breast (1237), colo-rectal (348) and prostate (432) cancer without evidence of metastases at dx or relapse 2y after dx and with fatigue information. Severe fatigue was defined as average score of EORTC QLQC30 fatigue subscale ≥40 at 2y after dx. There were

Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P

e18224Background: The optimal strategies for utilization of imaging and TM, and how to integrate both among MBC pts are unclear. Methods: In aretrospective cohort study of pts with de novo MBC trea...

e18031Background: Many studies have identified shortcomings with the quality of care for early stage breast cancer, but there is minimal research examining the quality of care for MBC. Methods: We ...

1577 Background: Significant improvements in survival time have been achieved for patients (pts) with MBC. Nevertheless, some still die soon after diagnosis. Data regarding features associated with...

561 Background: In randomized trials, administration of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) with G-CSF support improved outcomes compared with every 3 w...

611 Background: While 50-70% of pts with HER2+ MBC treated with T respond to therapy, the vast majority eventually develop resistance, after a median duration of 1 year. In rare cases, pts have exc...

646 Background: To characterize trastuzumab utilization and survival by race/ethnicity in older women with de novo stage IV breast cancer who were treated with trastuzumab. Methods: We used Surveil...

522 Background: We examined time trends of CT used and associations with pts characteristics in Stage I BC. Methods: Prospective cohort studyincluding pts with Stage I BC treated at a National Comprehensive Cancer Network center from 2000-09. We examined the proportion of pts receiving intensive vs. non-intensive CT over time.We defined an intensive regimen as: a combination of anthracyclines and taxanes (e.g. ACT ± H) or a combination of carboplatin and docetaxel (e.g. TCH), and non-intensive as: anthracycline-based (e.g. AC), taxane-based (e.g. TC) or similar. We evaluated factors associated with type of CT using multivariable logistic regression. Analyses were stratified by HER2 receptor status. Results: Of 8,907 pts, 33% received adjuvant CT. There was a dramatic increase of intensive CT: among HER2+ pts from 31% in 2000-05 to 63% in 2008-09 (including an increase in the use of TCH) and among HER2- from 15% in 2000-05 to 41% in 2008-09. Among non-intensive regimens there was an increase in the use of ...

TPS668 Background: As a single agent, eribulin is associated with prolonged overall survival compared to treatment of physician’s choice in pts with heavily pre-treated metastatic breast cancer (MB...

1006 Background: The role of adjuvant CTX in women with small BC is controversial. Here we analyze time trends of CTX use and outcomes in women with T1N0 BC treated at NCCN cancer centers. Methods: 8917 women were identified who received surgery or systemic therapy at an NCCN center with T1a, T1b or T1c N0 M0 BC between 2000-09. Tumors were grouped by biologic subgroups by hormone receptor (HR) and HER2 status and T subgroups (T1a, T1b, T1c). Primary endpoints were receipt of adjuvant CTX (± trastuzumab) and BC specific survival (BCSS). Chi-square, Cochran Armitage trend, Kaplan Meier estimates, log-rank test and Cox hazard proportional regression were used for analysis. In this report we focus on T1a/b results (N=4113). Results: Median follow up time was 5.5 years (range, 0.7-12.7). CTX use differed according to biologic and T subgroups, with significant changes over time (Table). In 2009, more than 50% of patients (pts) with HER2+ and HR-2- T1a/b breast cancers received CTX (± trastuzumab). The table lists use of CTX by year and subset and the 5 year BCSS for pts treated and not treated with CTX. Conclusions: A high proportion of pts with HER2+ and HR-HER2- T1N0 breast cancers received adjuvant CTX, with a sharp increase in use of CTX among HER2+ over the past decade. Use of CTX is higher in T1b compared to T1a tumors. In this study, women with T1a and T1b tumors have an excellent prognosis without CTX at 5 Yr. Careful examination of cutoffs for absolute benefit sufficient to recommend CTX is warranted. [Table: see text]

6089 Background: Benefits of CT vary widely in MBC pts. We aimed to describe the impact of breast cancer TS and line of tx on the duration of CT. Methods: In a retrospective analysis, we identified 205 pts treated with CT for MBC at the Dana-Farber Cancer Institute between 2005-8. TS were classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (TN) (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). CT duration was defined as "time from start of one CT line to the start of the next CT." Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used. Results: Median follow-up was 54 months (m). Most pts had received adjuvant tx, though 23% had MBC at diagnosis. Almost all HER2+ pts had concurrent anti-HER2 tx. CT duration was longest in 1st line with consecutive stepwise decrease. The proportion of pts who received CT beyond the 3rd line varied by TS: 52% of HER2+ pts received > 4 CT lines, compared with 37% of HR+ and 29% of TN pts. Duration in later CT lines also differed by TS. Median CT duration in HER2+ pts was > 4 m in all 6 lines, but HR+ and TN pts had a median CT duration of 6m of CT in 5th and 6th line; by contrast, CT duration for TN pts were consistently brief in later CT lines. Conclusions: TS determines the likely duration and number of lines of CT for MBC. Among HR+ and HER2+ pts who receive CT beyond 3rd line, there are substantial rates of prolonged tx suggesting clinical benefit. For TN pts, the opportunity for additional lines and the CT duration declined more dramatically. The true role of advanced (> 3rd) CT lines for all MBC in improving quality of life, survival, and the predictors of such benefit, warrant further study. [Table: see text]

599 Background: According to gene expression profiling, HER2+ BC is heterogeneous and appears to diverge by HR status. Methods: We evaluated 3394 pts who presented to NCCN centers with stage I-III HER2+ BC between 2000-07. Pts were classified as HR+ (ER+ and/or PR+) and HR- (ER- and PR-). Chi-square, univariate logistic regression, log-rank test, and Cox hazard proportional regression were used for analysis. Results: Median follow-up was 51 months. 59% of patients had HR+ and 41% HR- disease respectively. Pts with HR- BC were more likely to be postmenopausal and to present with higher stage and high grade disease (p