Long-term behavioral symptom clusters among survivors of early-stage breast cancer. development and validation of a predictive model.

BACKGROUND: Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms (CRBS) that may persist years after early-stage breast cancer (BC), affecting quality of life. We aimed at generating a predictive model of long-term CRBS clusters among BC survivors four years post-diagnosis. METHODS: Patients with early-stage BC were included from the CANcer TOxicity (NCT01993498). Our outcome was the proportion of patients reporting CRBS clusters four years post-diagnosis (≥3 severe CRBS). Predictors, including clinical, behavioral, and treatment-related characteristics, Behavioral Symptoms Score (BSS; 1 point per severe CRBS at diagnosis) and a pro-inflammatory cytokine (IL-1b, IL-6, TNFα)-genetic risk score, were tested using multivariable logistic regression, implementing bootstrapped Augmented Backwards Elimination. A two-sided p-value < 0.05 defined statistical significance. RESULTS: In the development cohort (N = 3555), 642 patients (19.0%) reported a cluster of CRBS at diagnosis and 755 (21.2%) did so four years post-diagnosis. Younger age (adjusted Odds Ratio [aOR] for 1-year decrement: 1.012; 95% Confidence Interval [CI] 1.003-1.020); previous psychiatric disorders (aOR vs no: 1.27; 95% CI 1.01-1.60); and BSS (aOR ranged from 2.17 [1.66-2.85] for BSS = 1 vs 0 to 12.3 [7.33-20.87] for BSS = 5 vs 0) were predictors of reporting a cluster of CRBS (AUC 0.73 [95%CI 0.71-0.75]). Genetic risk score was not predictive of CRBS. Results were confirmed in the validation cohort (N = 1533). CONCLUSION: Younger patients with previous psychiatric disorders and higher baseline symptom burden have greater risk of long-term clusters of CRBS. Our model might be implemented in clinical pathways to improve management and test the effectiveness of risk mitigation interventions among breast cancer survivors.

Evaluating the Implementation of Integrated Proactive Supportive Care Pathways in Oncology: Master Protocol for a Cohort Study.

BACKGROUND: Supportive care (SC) refers to the prevention and management of complications of cancer and its treatment. While it has long been recognized as an important cancer care delivery component, a high proportion of patients face unaddressed SC needs, calling for innovative approaches to deliver SC. OBJECTIVE: The objective of this master protocol is to evaluate the implementation of different integrated proactive SC pathways across the cancer care continuum in our institution (Gustave Roussy, Villejuif, France). Pathways studied in this master protocol may occur shortly after diagnosis to prevent treatment-related burden; during treatment to monitor the onset of toxicities and provide timely symptom management; and after treatment to improve rehabilitation, self-management skills, and social reintegration. METHODS: This study is guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. The primary objective is to evaluate the impact of SC pathways on patients' distress and unmet needs after 12 weeks, measured by the National Comprehensive Cancer Network's Distress Thermometer and Problem List. Secondary objectives will focus on the pathways (macrolevel) and each SC intervention (microlevel), evaluating their reach (administrative data review of the absolute number and proportion of clinical and sociodemographic characteristics of patients included in the pathways); short-term and long-term efficacy through their impact on quality of life (EQ-5D-5L and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire) and symptom burden (MD Anderson Symptom Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, and 22-item European Organization for Research and Treatment of Cancer Sexual Health Questionnaire); adoption by patients and providers (administrative data review of SC referrals and attendance or use of SC strategies); barriers to and leverage for implementation (surveys and focus groups with patients, providers, and the hospital organization); and maintenance (cost-consequence analysis). Pilot evaluations with a minimum of 70 patients per pathway will be performed to generate mean Distress Thermometer scores and SDs informing the calculation of formal sample size needed for efficacy evaluation (cohorts will be enriched accordingly). RESULTS: The study was approved by the ethics committee, and as of February 2024, a total of 12 patients were enrolled. CONCLUSIONS: This study will contribute toward innovative models of SC delivery and will inform the implementation of integrated SC pathways of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT06479057; https://clinicaltrials.gov/study/NCT06479057. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52841.

Cognition and Return to Work Status 2 Years After Breast Cancer Diagnosis.

Importance: Return to work after breast cancer (BC) treatment depends on several factors, including treatment-related adverse effects. While cancer-related cognitive impairment is frequently reported by patients with BC, to date, no longitudinal studies have assessed its association with return to work. Objective: To examine whether cognition, assessed using objective and subjective scores, was associated with return to work 2 years after BC diagnosis. Design, Setting, and Participants: In a case series of the French Cancer Toxicities (CANTO) cohort, a study of patients with stage I to III BC investigated cognition from April 2014 to December 2018 (2 years' follow-up). Participants included women aged 58 years or younger at BC diagnosis who were employed or looking for a job. Main Outcomes and Measures: The outcome was return to work assessed 2 years after BC diagnosis. Objective cognitive functioning (tests), cognitive symptoms, anxiety, depression, and fatigue were prospectively assessed at diagnosis (baseline), 1 year after treatment completion, and 2 years after diagnosis. Multivariable logistic regression models were used to explain return to work status at year 2 according to each cognitive measure separately, adjusted for age, occupational class, stage at diagnosis, and chemotherapy. Results: The final sample included 178 women with BC (median age: 48.7 [range, 28-58] years), including 37 (20.8%) who did not return to work at year 2. Patients who returned to work had a higher (ie, professional) occupational class and were less likely to have had a mastectomy (24.1% vs 54.1%; P < .001). Return to work at year 2 was associated with lower overall cognitive impairment (1-point unit of increased odds ratio [1-pt OR], 0.32; 95% CI, 0.13-0.79; P = .01), higher working memory (1-pt OR, 2.06; 95% CI, 1.23-3.59; P = .008), higher processing speed (1-pt OR, 1.97; 95% CI, 1.20-3.36; P = .01) and higher attention performance (1-pt OR, 1.63; 95% CI, 1.04-2.64; P = .04), higher perceived cognitive abilities (1-pt OR, 1.12; 95% CI, 1.03-1.21; P = .007), and lower depression (1-pt OR, 0.83; 95% CI, 0.74-0.93; P = .001) at year 2 assessment. Return to work at year 2 was associated with several measures assessed at baseline and year 1: higher processing speed (1-pt OR, 2.38; 95% CI, 1.37-4.31; P = .003 and 1.95; 95% CI, 1.14-3.50; P = .02), higher executive performance (1-pt OR, 2.61; 95% CI, 1.28-5.75; P = .01, and 2.88; 95% CI, 1.36-6.28; P = .006), and lower physical fatigue (10-pt OR, 0.81; 95% CI, 0.69-0.95; P = .009 and 0.84; 95% CI, 0.71-0.98; P = .02). Conclusions and Relevance: In this case series study of patients with BC, return to work 2 years after diagnosis was associated with higher cognitive speed performance before and after BC treatment. Cognitive difficulties should be assessed before return to work to propose suitable management.

Metabolomic prediction of breast cancer treatment induced neurological and metabolic toxicities.

BACKGROUND: Long-term treatment-related toxicities, such as neurological and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities. METHODS: Untargeted high-resolution metabolomic profiles of 992 patients with ER+/HER2- breast cancer from the prospective CANTO cohort were acquired (n=1935 metabolites). A residual-based modeling strategy with a discovery and validation cohort was used to benchmark machine learning algorithms, taking into account confounding variables. RESULTS: Adaptive LASSO has a good predictive performance, has limited optimism bias, and allows the selection of metabolites of interest for future translational research. The addition of low-frequency metabolites and non-annotated metabolites increases the predictive power. Metabolomics adds extra performance to clinical variables to predict various neurological and metabolic toxicity profiles. CONCLUSIONS: Untargeted high-resolution metabolomics allows better toxicity prediction by considering environmental exposure, metabolites linked to microbiota, and low-frequency metabolites.

Dose/Exposure Relationship of Exercise and Distant Recurrence in Primary Breast Cancer.

PURPOSE: Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC. METHODS: Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task-hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs). RESULTS: For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor-/human epidermal growth factor receptor 2- (HR-/HER2-; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR-/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population. CONCLUSION: Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.

Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort.

PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial.

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Breast cancer survivors' opinion on personalizing endocrine therapy and developing informative tools.

Understanding breast cancer survivors' perspectives is critical to personalizing endocrine therapy (ET) in the adjuvant setting. A nationwide survey among breast cancer survivors was proposed in France, in collaboration with patient advocacy organizations, to assess their perspectives on personalizing ET and developing dedicated informative tools. This survey explored patients' preferences regarding ET intake schedule, formulation, presentation (color, taste, shape, size, design, and packaging), combination with agents targeting ET-related adverse events, and a mobile application to support them during ET. Of the 1103 individuals who started the survey, 939 (85.1%) were eligible for enrollment and completed the survey. The majority of the participants considered that a personalized ET should take into consideration the intake schedule (n = 974, 90.7%) and swallowable tablet formulation (n = 606, 64.5%), without a preference for ET presentation (n = 619; 65.9%). The majority of the participants expressed a willingness to participate in a potential clinical trial evaluating the combination of ET with agents targeting ET-related adverse events at the start of ET (n = 752, 80.1%) or in the case of major ET-related adverse events (n = 778, 82.8%). The primary considerations were to have an uncompromised ET efficacy and a guaranteed reduction of adverse events. Last, a dedicated mobile application was considered helpful by 665 participants (70.8%). Informative tools should focus on the recommendations for dealing with adverse events (n = 593, 63.2%), the impact on the patient's daily life (n = 515, 54.9%), benefits (n = 504, 53.7%), and adverse events (n = 494, 52.6%) of ET. This survey paves the way for multimodal strategies that can include a personalized ET (e.g., ET in combination with agents targeting ET-related adverse events) and dedicated mobile applications to ultimately improve adherence.

Inflammation at diagnosis and cognitive impairment two years later in breast cancer patients from the Canto-Cog study.

BACKGROUND: Inflammation could be related to cancer-related cognitive impairment (CRCI) and might be used as a predictive marker of long-term CRCI. We evaluated associations between inflammatory markers assessed at diagnosis of breast cancer and CRCI two years afterwards. METHODS: Newly diagnosed stage I-III patients with breast cancer from the French CANTO-Cog (Cognitive sub-study of CANTO, NCT01993498) were included at diagnosis (baseline). Serum inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, CRP) were assessed at baseline. Outcomes at year 2 post-baseline included overall cognitive impairment (≥ 2 impaired domains) and the following domains: episodic memory, working memory, attention, processing speed, and executive functions. Multivariable logistic regression models evaluated associations between markers and outcomes, controlling for age, education, and baseline cognitive impairment. RESULTS: Among 200 patients, the mean age was 54 ± 11 years, with 127 (64%) receiving chemotherapy. Fifty-three (27%) patients had overall cognitive impairment at both timepoints. Overall cognitive impairment at year 2 was associated with high (> 3 mg/L) baseline CRP (OR = 2.84, 95%CI: 1.06-7.64, p = 0.037). In addition, associations were found between high CRP and processing speed impairment (OR = 2.47, 95%CI:1.05-5.87, p = 0.039), and between high IL-6 and episodic memory impairment (OR = 5.50, 95%CI:1.43-36.6, p = 0.010). CONCLUSIONS: In this cohort, high levels of CRP and IL-6 assessed at diagnosis were associated with overall CRCI, processing speed and episodic memory impairments two years later. These findings suggest a potential inflammatory basis for long-term CRCI. CRP may represent an easily measurable marker in clinical settings and be potentially used to screen patients at greater risk of persistent CRCI.

Patient-Reported Quality of Life 6 Years After Breast Cancer.

This cohort study assesses quality-of-life trajectories up to 6 years after breast cancer diagnosis among individuals in France.

Chemotherapy-Related Amenorrhea and Quality of Life Among Premenopausal Women With Breast Cancer.

Importance: Younger survivors of breast cancer frequently report more treatment-related symptoms, mostly related to the menopausal transition. Objective: To assess factors associated with chemotherapy-related amenorrhea (CRA) and to evaluate its association with long-term quality of life (QOL). Design, Setting, and Participants: The prospective, longitudinal Cancer Toxicities Study, a multicenter French cohort study, includes women with a diagnosis of stage I to III breast cancer and collects data approximately yearly after diagnosis. The current study reports outcomes up to 4 years after diagnosis for participants enrolled from 2012 to 2017. Participants included premenopausal women younger than 50 years treated with chemotherapy and not receiving adjuvant ovarian function suppression. Data analysis was performed from September 2021 to June 2023. Exposures: Clinical, socioeconomic, tumor, and treatment characteristics assessed at diagnosis (for the analysis of factors associated with CRA) and persistent CRA (for the QOL analysis). Main Outcomes and Measures: The main outcome of interest was CRA at year 1 (Y1), year 2 (Y2), and year 4 (Y4) after diagnosis. Generalized estimating equations assessed associations of exposure variables with CRA. In the QOL analysis, QOL at Y4 (assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BR23) was the outcome of interest. Multivariable random-effect mixed models assessed the association of persistent CRA (ie, never recovering menses after treatment) with QOL. Results: Among 1636 women, the mean (SD) age at diagnosis was 42.2 (5.6) years. Overall, 1242 of 1497 women (83.0%) reported CRA at Y1, 959 of 1323 women (72.5%) reported it at Y2, and 599 of 906 women (66.1%) reported it at Y4. Older age vs 18 to 34 years (adjusted odds ratio [OR] for 35 to 39 years, 1.84 [95% CI, 1.32 to 2.56]; adjusted OR for 40 to 44 years, 5.90 [95% CI, 4.23 to 8.24]; and adjusted OR for ≥45 years, 21.29 [95% CI, 14.34 to 31.61]) and receipt of adjuvant tamoxifen (adjusted OR, 1.97 [95% CI, 1.53 to 2.53]) were associated with higher likelihood of CRA. In the QOL analysis, 416 of 729 women (57.1%) had persistent CRA. However, late menses recovery among women aged 18 to 34 years with no menses at Y2 were reported by 11 of 21 women (52.4%) between Y2 and Y4. Persistent CRA was associated with worse insomnia (mean difference vs recovery at any time, 9.9 points [95% CI, 3.2 to 16.5 points]; P = .004), systemic therapy-related adverse effects (mean difference, 3.0 points [95% CI, 0.2 to 5.8 points]; P = .04), and sexual functioning (mean difference, -9.2 points [95% CI, -14.3 to -4.1 points]; P < .001) at Y4. Conclusions and Relevance: In this cohort study of premenopausal women with breast cancer, persistent CRA was common, although some women recovered menses late, and was associated with worse long-term QOL. This study can help inform risk communication, personalized counseling, and early supportive care referrals for such patients.

Insights adjusting for non-adherence in randomized clinical trials: a reanalysis of an adjuvant trial of tamoxifen duration in early breast cancer.

BACKGROUND: Several randomized clinical trials provide evidence of the survival benefit of extended adjuvant tamoxifen in women with estrogen receptor (ER)-positive early breast cancer (BC). However, non-adherence may lead to underestimate treatment effects using intention to treat (ITT) methods. We reanalyzed a randomized trial using contemporary statistical methods adjusting for non-adherence. METHODS: The TAM01 study was a phase 3 trial including women with early BC, who had completed 2-3 years of adjuvant tamoxifen between 1986 and 1995. Participants were randomly assigned to continue tamoxifen up to 10 years or to discontinue the treatment at randomization. Invasive disease-free survival (iDFS) and overall survival (OS) were estimated using marginal structural models (MSM) and rank preserving structural failure time model (RPSFTM). RESULTS: Of 3830 patients enrolled, 2485 were randomized to extended tamoxifen, and 1345 to treatment discontinuation. The 10-year non-adherence rate in the extended group was 27.2%. Among women with ER-positive BC (n = 2402), extended tamoxifen was associated with a 45% and 21% relative improvement in iDFS by MSM and RPSFTM, respectively (Hazard Ratio (HR), 0.55; 95% Confidence Interval (CI), 0.48-0.64 and HR, 0.79; 95%CI, 0.67-0.95, respectively), a considerable greater benefit than in the ITT analysis (HR, 0.90; 95%CI, 0.81-0.99). The OS reanalysis revealed a substantial benefit of extended tamoxifen (MSM: HR, 0.70; 95%CI, 0.59-0.83; RPSFTM: HR, 0.85; 95%CI, 0.67-1.04), compared to the ITT analyses (HR, 0.94; 95%CI, 0.84-1.07). CONCLUSION: This analysis emphasizes both the importance of adherence to hormonotherapy in hormone-receptor positive early BC and the usefulness of more complex statistical analyses.

Sustainable return to work among breast cancer survivors.

PURPOSE: This study assessed sustainable return to work (SRTW) of breast cancer survivors (BCS). METHODS: We used data from the prospective French cohort, CANTO. We included 1811 stage I-III BCS who were <57 years old and employed at the moment of diagnosis and working 2 years after diagnosis. Using logistic regression, we investigated the role of clinical, health and socio-economic factors, and the work environment on SRTW 3 years after diagnosis. We compared having any sick leave with having worked continuously and being unemployed to having worked continuously between 2 and 3 years after diagnosis. RESULTS: Overall, 77% (n = 1395) worked continuously after return to work (RTW). Out of the other 416 BCS, 66% had any sick leave period, 33% had been unemployed, 4% had an early retirement, 2% a disability and 1% another status (multiple situations possible). Being on sick leave was associated with age > 50 (OR = 0.59; 95%CI = 0.43-0.82), stage III (2.56; 1.70-3.85), tumour subtype HR+/HER2+ (0.61; 0.39-0.95), severe fatigue (1.45; 1.06-1.98), workplace accommodations (1.63; 1.14-2.33) and life priorities (0.71; 0.53-0.95). Unemployment was associated with age > 50 (0.45; 0.29-0.72), working in the public sector (0.31; 0.19-0.51), for a small company (3.00; 1.74-5.20) and having a fixed-term contract (7.50; 4.74-11.86). CONCLUSIONS: A high number of BCS have periods of sick leave or unemployment after RTW. The determinants differ between sick leave and unemployment. IMPLICATIONS FOR CANCER SURVIVORS: BCS need to be supported even after RTW, which should be regarded as a process.

Adjuvant endocrine therapy uptake, toxicity, quality of life, and prediction of early discontinuation.

BACKGROUND: Many patients receiving adjuvant endocrine therapy (ET) for breast cancer experience side effects and reduced quality of life (QoL) and discontinue ET. We sought to describe these issues and develop a prediction model of early discontinuation of ET. METHODS: Among patients with hormone receptor-positive and HER2-negative stage I-III breast cancer of the Cancer Toxicities cohort (NCT01993498) who were prescribed adjuvant ET between 2012 and 2017, upon stratification by menopausal status, we evaluated adjuvant ET patterns including treatment change and patient-reported discontinuation and ET-associated toxicities and impact on QoL. Independent variables included clinical and demographic features, toxicities, and patient-reported outcomes. A machine-learning model to predict time to early discontinuation was trained and evaluated on a held-out validation set. RESULTS: Patient-reported discontinuation rate of the first prescribed ET at 4 years was 30% and 35% in 4122 postmenopausal and 2087 premenopausal patients, respectively. Switching to a new ET was associated with higher symptom burden, poorer QoL, and higher discontinuation rate. Early discontinuation rate of adjuvant ET before treatment completion was 13% in postmenopausal and 15% in premenopausal patients. The early discontinuation model obtained a C index of 0.62 in the held-out validation set. Many aspects of QoL, most importantly fatigue and insomnia (European Organization for Research and Treatment of Cancer QoL questionnaire 30), were associated with early discontinuation. CONCLUSION: Tolerability and adherence to ET remains a challenge for patients who switch to a second ET. An early discontinuation model using patient-reported outcomes identifies patients likely to discontinue their adjuvant ET. Improved management of toxicities and novel more tolerable adjuvant ETs are needed for maintaining patients on treatment.

Implementing a PROACTive Care Pathway to Empower and Support Survivors of Breast Cancer.

PURPOSE: Optimal comprehensive survivorship care is insufficiently delivered. To increase patient empowerment and maximize the uptake of multidisciplinary supportive care strategies to serve all survivorship needs, we implemented a proactive survivorship care pathway for patients with early breast cancer at the end of primary treatment phase. METHODS: Pathway components included (1) a personalized survivorship care plan (SCP), (2) face-to-face survivorship education seminars and personalized consultation for supportive care referrals (Transition Day), (3) a mobile app delivering personalized education and self-management advice, and (4) decision aids for physicians focused on supportive care needs. A mixed-methods process evaluation was performed according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework including administrative data review, pathway experience survey (patient, physician, and organization), and focus group. The primary objective was patient-perceived satisfaction with the pathway (predefined progression criteria for pathway continuation ≥70%). RESULTS: Over 6 months, 321 patients were eligible for the pathway and received a SCP and 98 (30%) attended the Transition Day. Among 126 patients surveyed, 77 (66.1%) responded. 70.1% received the SCP, 51.9% attended the Transition Day, and 59.7% accessed the mobile app. 96.1% of patients were very or completely satisfied with the overall pathway, whereas perceived usefulness was 64.8% for the SCP, 90% for the Transition Day, and 65.2% for the mobile app. Pathway implementation seemed to be positively experienced by physicians and the organization. CONCLUSION: Patients were satisfied with a proactive survivorship care pathway, and the majority reported that its components were useful in supporting their needs. This study can inform the implementation of survivorship care pathways in other centers.

Baseline quality of life and chemotherapy toxicities in patients with early breast cancer.

BACKGROUND: The authors used the French breast cancer Cancer and Toxicities (CANTO) cohort to study the associations between baseline quality of life and chemotherapy dose-reductions (CDRs) or postchemotherapy-toxicities (PCTs). METHODS: In total, 3079 patients with breast cancer who received chemotherapy were included in this analysis. The associations between baseline physical functioning (PF) and fatigue measured using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30, and two endpoints-CDRs during adjuvant or neoadjuvant chemotherapy; and selected PCTs were estimated with odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) using logistic regression models. RESULTS: Among the 3079 patients from the CANTO cohort who were included, 718 (33.0%) received chemotherapy in the neoadjuvant setting, and 2361 (67.0%) received chemotherapy as adjuvant treatment. The chemotherapy included taxanes in 94.2% of patients and anthracyclines in 90.5% of patients. Overall, 15.5% of patients experienced CDRs and, 31.0% developed PCTs. Women with low baseline PF scores (<83) had higher multivariate odds of developing CDRs compared with those who had PF scores ≥83 (OR, 1.54; 95% CI, 1.13-2.09). The corresponding OR for PCTs was 1.50 (95% CI, 1.13-2.00). Women with high baseline fatigue scores had higher odds of CDRs (OR, 1.43; 95% CI, 1.13-1.76) and PCTs (OR, 1.32; 95% CI, 1.10-1.59). CONCLUSIONS: By using the national CANTO cohort, baseline PF and fatigue were independently associated with CDRs and PCTs.

Change in the value of work after breast cancer: evidence from a prospective cohort.

BACKGROUND: Return to work (RTW) after cancer can be modulated by psychosocial factors, including a reordering of one's life values, with more emphasis on private life than work-life. This change in patients' outlook on work-life is however poorly understood. METHODS: We used data from a French cohort (CANTO, NCT01993498) of women diagnosed with stage I-III primary breast cancer (BC) prospectively assessing life priorities between work and private life at diagnosis and 2 years after diagnosis. We identified women who reported a shift in life values toward private life, and we investigated the clinical, demographic, work-related, and psychosocial determinants of this change using logistic regressions. RESULTS: Overall, 46% (N = 1097) of the women had reordered their life priorities toward private life 2 years after diagnosis. The factors positively associated with this shift included being diagnosed with stage III BC, perceiving one's job as not very interesting, being an employee/clerk (vs. executive occupation), perceiving no support from the supervisor at baseline, perceiving negative interferences of cancer in daily life, and perceiving a positive impact from experiencing cancer. Depressive symptoms were negatively associated with this shift. CONCLUSION: After BC, there seems to be an important reordering of life values, with more emphasis on private life. This change is influenced by clinical determinants, but also by work-related and psychosocial factors. IMPLICATIONS FOR CANCER SURVIVORS: Stakeholders should consider this change in a patient's outlook on work-life as much as the classical physical late effects when designing post-BC programs to support RTW.

Cognitive change in breast cancer patients up to 2 years after diagnosis.

BACKGROUND: Using the large nationwide French, national, multicenter, prospective cancer and toxicities (CANTO) cohort, we assessed cognitive functioning change after cancer treatments in a subgroup of breast cancer (BC) patients. METHODS: We included patients with newly diagnosed invasive stage I-III BC enrolled in the CANTO substudy focused on cognitive evaluation and healthy control women matched for age and education. Episodic and working memory, executive functions, processing speed, attention, self-report cognitive difficulties (SRCD), fatigue, anxiety and depression were assessed with neuropsychological tests and self-report questionnaires before treatment (baseline) and approximately 1 (year 1) and 2 years (year 2) after diagnosis. We used linear mixed models to study changes in cognition and tested the effect of adjuvant chemotherapy. RESULTS: We studied 276 localized BC patients (62% chemotherapy) compared with 135 healthy controls (HC). After adjustment, patients had lower baseline working memory, processing speed, and attention scores than HC (P ≤ .001), and the difference remained statistically significant over follow-up for working memory and processing speed. Executive function scores were similar between groups at baseline but decreased at year 1 among patients compared with HC (Pchange = .006). This decrease in chemotherapy patients was statistically significant compared with HC scores (Pchange < .001). After adjustment, SRCD were similar between BC patients and HC at baseline but increased in patients after treatment at year 1 (Pchange = .002). CONCLUSIONS: Cognitive difficulties are an important concern in BC patients, starting at diagnosis. Cancer treatments induce executive function decline and SRCD, which decrease over follow-up.