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.

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.

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.

Coffee and tea consumption, patient-reported, and clinical outcomes in a longitudinal study of patients with breast cancer.

BACKGROUND: Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient-reported outcomes (PROs) and clinical outcomes among survivors of BC. METHODS: The authors included survivors of stage I-III BC enrolled in the CANTO cohort (NCT01993498) that provided post-treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group-based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes. RESULTS: Among 3788 patients, the authors identified four stable patterns of consumption: "Low" (25.8%), "Moderate" (37.6%), "High" (25.3%), and "Very high" (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the "Very high" group (vs. "Low"), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups. CONCLUSIONS: Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes.

Association between physical activity and neoadjuvant chemotherapy completion and pathologic complete response in primary breast cancer: the CANTO study.

BACKGROUND: Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear. METHODS: Using a prospective design, 1075 breast cancer patients receiving neoadjuvant chemotherapy between March 2012 and February 2017 were studied. Physical activity was assessed using the Global Physical Activity Questionnaire [GPAQ-16], quantified in standardised MET-h/wk. Chemotherapy completion was defined as the proportion of patients completing planned treatment course, requiring dose reduction, or requiring dose delay. Response was evaluated by pathologic complete response (pCR). Associations between physical activity and primary outcomes were assessed using multivariable logistic regression models. RESULTS: There was no differences between any chemotherapy completion outcome on the basis of physical activity classification. The percent of patients not completing planned treatment was 5.7% for ≦0.33 MET-h/wk, compared with 6.8% for 0.34-16.65 MET-h/wk, and 4.6% for ≥16.6 MET-h/wk (p = 0.52). No significant relationships were observed between physical activity dose classification and pCR for the overall cohort or upon stratification by clinical subtype. CONCLUSION: Future studies are required to further investigate the relationship between pre-treatment levels of physical activity and function on treatment completion and response in breast and other cancer populations. CLINICAL TRIAL REGISTRATION: NCT01993498.

Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind-body techniques, whereas no data show benefit for homeopathy or naturopathy. METHODS: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I-III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. RESULTS: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71-0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05-1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10-1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17-1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23-1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63-0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06-1.79; P=.017). CONCLUSIONS: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.

Informing the development of multidisciplinary interventions to help breast cancer patients return to work: a qualitative study.

PURPOSE: Return to work (RTW) after breast cancer (BC) can be a major challenge for patients. Multidisciplinary interventions seem to be effective but the role of digital solutions is under-developed and therefore not evaluated. We explored the preferences, needs, and barriers regarding RTW interventions, including opinions about the use of digital approaches to deliver such interventions. METHODS: We conducted a qualitative study based on interviews with 30 patients with BC and 18 healthcare providers in four French regions. Emergent themes were identified using thematic content analysis. RESULTS: Most providers declared that they did not proactively address RTW with patients, mainly due to having other priorities and a lack of knowledge. The following themes emerged: several development and deployment barriers regarding RTW interventions exist, multidisciplinary interventions are preferred, and there is a need to maintain contact between the patient and workplace during sick leave, including pathways and interlocutors that can facilitate RTW. Participants had mostly positive representations of using digital tools to facilitate RTW; however, fear of loss of human contact and the exacerbation of inequalities were identified as possible risks associated with the development of digital-only interventions. CONCLUSIONS: Interventions blending the needs and preferences of patients with BC and the healthcare system are warranted. A personalized multimodal approach with mixed digital and in-person features has surfaced as a possible solution to address the weaknesses of existing interventions. IMPLICATIONS FOR CANCER SURVIVORS: Since most women work at the time of diagnosis, it is of particular relevance to build interventions promoting RTW.

BEAUTY and the breast: is adjuvant chemotherapy the right time for a beauty boost? Lessons learned from a large randomized controlled trial.

PURPOSE: Beauty care (BTC) is offered at many cancer hospitals having a great uptake among patients. Nevertheless, its benefits in the Quality of life (QoL) of cancer survivors have not been assessed so far. METHODS: Our study aims to determine whether BTC improves patients' QoL related to their body image measured by the BRBI scale of the QLQ-BR23 questionnaire at the end of adjuvant chemotherapy, after breast cancer (BC) surgery. The BEAUTY study is a prospective, randomized, controlled intervention trial. The following patient-reported outcomes were filled before initiation of chemotherapy (T1) and after their last cycle (T2): EORTC QLQ-C30, QLQ-BR23, and Body Image Scale (BIS). Primary objective was improvement in the BIS of BR23 (BRBI). A qualitative assessment of patients' experience was performed at each cycle through a relevant questionnaire. RESULTS: In total, 269 (67%) patients filled BRBI at T1 and T2. Mean BRBI scores substantially decreased between T1 and T2 and were not different with or without BTC (p = 0.88). Qualitative assessment suggests impact of BTC in physical well-being and avoids thoughts related to the disease. CONCLUSION: A substantial proportion of patients have a poor body image and chemotherapy induced a substantial degradation of BRBI scores. Although BTC does not seem to impact BRBI scores, the qualitative assessment suggests some benefit of BTC in other domains. Our study highlights the need to assess patients-perceived body image and build tailored interventions at this critical phase of their disease and generates hypothesis for the impact of BTC among BC patients. Clinical trial registration The study is registered at ClinicalTrials.gov under the NCT01459003 number since October 25, 2011.

Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.

Clinical behavior of recurrent hormone receptor-positive breast cancer by adjuvant endocrine therapy within the Breast International Group 1-98 clinical trial.

BACKGROUND: Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor-positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1-98 trial. METHODS: BIG 1-98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow-up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post-DR survival. RESULTS: The median follow-up time after DR was 59 months (interquartile range, 29-88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post-DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P = .21). In multivariate analysis, older patients (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.15-1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00-1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05-1.64), progesterone receptor (PR)-negative tumors (HR, 1.25; 95% CI, 1.02-1.52), or shorter disease-free survival (DFS) had significantly worse post-DR survival. CONCLUSIONS: Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high-risk features remain prognostic in the metastatic setting.

Unhealthy behaviors after breast cancer: Capitalizing on a teachable moment to promote lifestyle improvements.

BACKGROUND: This study assessed the prevalence and risk factors of unhealthy behaviors among survivors of early-stage breast cancer. METHODS: Women (n = 9556) from the CANcer TOxicity cohort (NCT01993498) were included. Physical activity (PA), tobacco and alcohol consumption, and body mass index were assessed at diagnosis and at years 1 and 2 after diagnosis. A behavior was defined as unhealthy if patients failed to meet PA recommendations (≥10 metabolic equivalent task hours per week), reduce/quit tobacco, or decrease alcohol consumption to less than daily, or if they gained substantial weight over time. Multivariable-adjusted generalized estimating equations explored associations with unhealthy behaviors. RESULTS: At diagnosis, 41.7% of patients were inactive, 18.2% currently used tobacco, 14.6% consumed alcohol daily, and 48.9% were overweight or obese. At years 1 and 2, unhealthy PA behavior was reported among 37.0% and 35.6% of patients, respectively, unhealthy tobacco use behavior was reported among 11.4% and 9.5%, respectively, and unhealthy alcohol behavior was reported among 13.1% and 12.6%, respectively. In comparison with the previous assessment, 9.4% and 5.9% of underweight and normal-weight patients had transitioned to the overweight or obese category at years 1 and 2, respectively, and 15.4% and 16.2% of overweight and obese patients had gained ≥5% of their weight at years 1 and 2, respectively. One in 3 current tobacco smokers and 1 in 10 daily alcohol users reported improved behaviors after diagnosis. Older women (5-year increment) were more likely to be inactive (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 1.01-1.05) and report unhealthy alcohol behavior (aOR, 1.28; 95% CI, 1.23-1.33) but were less likely to engage in unhealthy tobacco use (aOR, 0.81; 95% CI, 0.78-0.85). Being at risk for depression (vs not being at risk for depression) was associated with reduced odds of unhealthy tobacco use (aOR, 0.67; 95% CI, 0.46-0.97) and with a higher likelihood of unhealthy alcohol behavior (aOR, 1.58; 95% CI, 1.14-2.19). Women with a college education (vs a primary school education) less frequently reported an unhealthy PA behavior (aOR, 0.61; 95% CI, 0.51-0.73) and were more likely to report unhealthy alcohol behavior (aOR, 1.85; 95% CI, 1.37-2.49). Receipt of chemotherapy (vs not receiving chemotherapy) was associated with higher odds of gaining weight (aOR, 1.51; 95% CI, 1.23-1.87) among those who were overweight or obese at diagnosis. CONCLUSIONS: The majority of women were adherent to healthy lifestyle behaviors at the time of their breast cancer diagnosis, but a significant subset was nonadherent. Unhealthy behaviors tended to persist after the breast cancer diagnosis, having varying clinical, psychological, sociodemographic, and treatment-related determinants. This study will inform more targeted interventions to promote optimal health.

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer.

BACKGROUND: In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)-paclitaxel regimen. PATIENTS, MATERIALS, AND METHODS: In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I-III breast cancer received paclitaxel 175 mg/m2 every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3-4 HSRs. RESULTS: Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%-20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%-6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%-5.0%), 6.5% (3.3%-11.3%), 7.4% (3.9%-12.5%), and 2.6% (0.7%-6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%-2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%-6.8%) and 0.9% (1/109; 0.05%-4.3%) of patients in cycle 3 and 4, respectively. CONCLUSION: Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2. IMPLICATIONS FOR PRACTICE: Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer.

PURPOSE: There are limited data on trastuzumab-pertuzumab (HP)-based treatments beyond the first-line, HER2+ metastatic breast cancer (MBC) setting. We conducted a phase II study of eribulin mesylate, which extends survival in MBC, with HP in patients with previously treated HER2+ MBC to evaluate efficacy, toxicity, and genomic alterations driving therapeutic response. METHODS: After a run-in phase for eribulin dosing, two cohorts were enrolled (Cohort A-no prior pertuzumab; Cohort B-prior pertuzumab). All patients received eribulin 1.4 mg/m2 on days 1, 8 with standard-dose HP on day 1 (21-day cycles). The primary endpoint was objective response rate (ORR). Genomic characterization via whole exome sequencing (WES) was completed on tumor DNA and matched germline DNA from 19 patients. RESULTS: The six-patient run-in established a dose of eribulin 1.4 mg/m2 with HP. Cohorts A and B enrolled 17 and 7 patients, respectively. Accrual stopped early due to an evolving treatment landscape and slow enrollment. The ORR was 26.3% (95% Confidence Interval [CI] 9.2-51.2%) in Cohort A and 0% in Cohort B (95% CI 0-41.0%). WES revealed more frequent alterations in TP53 (p < 0.05, q > 0.05) in patients without clinical benefit (disease control for < 24 weeks) which was not significant after multiple hypothesis correction. CONCLUSION: Eribulin-HP had manageable toxicity and modest clinical activity in patients without prior pertuzumab exposure. This study provides a preliminary landscape of somatic alterations in this patient cohort. Our data add to the literature on how genomic alterations may predict for therapy response/resistance, as we work to individualize choices in a quickly evolving HER2+ MBC treatment landscape. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT01912963. Registered 24 July 2013.

Determinants of use of oral complementary-alternative medicine among women with early breast cancer: a focus on cancer-related fatigue.

BACKGROUND: Despite the questionable effectiveness of oral complementary and alternative medicine (OCAM) in relieving cancer-related symptoms, including fatigue (CRF), many patients use it aiming to improve their quality of life. We assessed factors associated with OCAM use, focusing on CRF. METHODS: Women with stage I-III breast cancer (BC) were included from CANTO (NCT01993498). OCAM use was defined as taking homeopathy, vitamins/minerals, or herbal/dietary supplements. Multivariable multinomial logistic regressions evaluated associations of CRF (EORTC QLQ-C30), patient, and treatment characteristics with OCAM use. RESULTS: Among 5237 women, 23.0% reported OCAM use overall (49.3% at diagnosis, 50.7% starting post-diagnosis), mostly homeopathy (65.4%). Mean (SD) CRF score was 27.6 (24.0) at diagnosis and 35.1 (25.3) at post-diagnosis. More intense CRF was consistently associated with OCAM use at diagnosis and post-diagnosis [adjusted odds ratio (aOR) for 10-point increase 1.05 (95% Confidence interval 1.01-1.09) and 1.04 (1.01-1.09) vs. never use, respectively]. Odds of using OCAM at diagnosis were higher among older [for 5-year increase, 1.09 (1.04-1.14)] and more educated patients [college vs. primary 1.80 (1.27-2.55)]. Women with income > 3000 [vs. < 1500 euros/month, 1.44 (1.02-2.03)], anxiety [vs. not, 1.25 (1.01-1.54)], and those receiving chemotherapy [vs. not, 1.32 (1.04-1.68)] had higher odds of using OCAM post-diagnosis. CONCLUSION: One-in-four patients reported use of OCAM. More severe CRF was consistently associated with its use. Moreover, older, better educated, wealthier, more anxious women, and those receiving chemotherapy seemed more prone to use OCAM. Characterizing profiles of BC patients more frequently resorting to OCAM may help deliver targeted information about its benefits and potential risks.

Lifestyle and quality of life in patients with early-stage breast cancer receiving adjuvant endocrine therapy.

PURPOSE OF REVIEW: A comprehensive approach to survivorship care for women with early-stage, hormone-receptor positive breast cancer should systematically include the proactive assessment and adequate management of endocrine therapy-associated symptoms, in order to assure optimal balance between preserving quality of life (QOL) and maximizing treatment adherence. We reviewed the recent literature focused on lifestyle factors, including physical activity, diet and nutrition, weight management, smoke, and alcohol behavior, and their link with symptomatology and QOL among women receiving adjuvant endocrine therapy. RECENT FINDINGS: Recent studies confirm the safety, feasibility, and effectiveness of lifestyle interventions in mitigating several common endocrine therapy-related effects, including musculoskeletal pain, fatigue, and insomnia, and in improving physical and emotional wellbeing as well as overall health-related QOL among women with early-stage breast cancer. SUMMARY: Healthy lifestyle behaviors have the potential to modulate the downstream impact of endocrine therapy and improve QOL among women with early-stage breast cancer. Considerations for real-world clinical care implementation emerged, including a need to evaluate the long-term uptake of healthy behaviors and facilitate the postintervention maintenance of an improved lifestyle. Some facilitators to health promotion in breast cancer survivors were also suggested, such as individualized and one-to-one supervised programs, and digital solutions providing real-time feedback, building on personalized, direct patient engagement.

Differentiation of groups of patients with cognitive complaints at breast cancer diagnosis: Results from a sub-study of the French CANTO cohort.

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.

QualFatigue study: which factors influence the use of specific interventions for breast cancer survivors with fatigue? A cross-sectional exploratory study.

PURPOSE: International guidelines recommend specific interventions to reduce cancer-related fatigue (CRF). Evidence suggests underutilization of these interventions among breast cancer survivors. The QualFatigue study aimed to explore the potential factors influencing the use of specific interventions, for relief, in patients with CRF through qualitative analyses. METHODS: Patients with stage I-III breast cancer, and CRF ≥4 on a 10-point numerical scale were recruited within 6-24 months at the end of their primary treatment. Semi-structured interviews were performed. Emergent themes were identified using a stepped content analysis (QDA Miner software). RESULTS: Data saturation was achieved with 15 interviews. Four main themes emerged as potential sources of influence in the participants' use of specific interventions: (1) expectations regarding the management of CRF, (2) representations of the benefits provided by the interventions, (3) individual physical and psychological conditions, and (4) social and environmental situations. Six key levers came out transversally to optimize the use of specific interventions to relieve CRF: (1) listening and recognition of the individual difficulties and needs; (2) individual and global health assessments; (3) information and advice on how to manage CRF; (4) discussion groups focused on the management of CRF; (5) group activities; and (6) professional and personalized guidance. CONCLUSION: This study calls for multi-level action to address many persistent barriers and exploit levers in the management of CRF.

A qualitative evaluation of the use of interventions to treat fatigue among cancer survivors: A healthcare provider's view.

OBJECTIVE: Cancer-related fatigue (CRF) is among the most common and distressing side effects of cancer treatment. Different types of interventions, including physical activity (PA), psychosocial and mind-body interventions, have been shown to reduce CRF. We aimed to explore HCPs' practices and barriers to refer patients towards interventions to reduce CRF. METHODS: We performed a qualitative study using key informant interviews among a sample of 20 HCPs including medical, surgical and radiation oncologists, pain specialists, nurses, psychologists, psychiatrists and physiotherapists recruited from breast, prostate and colorectal cancer disease groups from a comprehensive cancer centre. RESULTS: Most interviewees reported not to address CRF spontaneously during consultations. When the topic of CRF was brought up by patients, all interviewees acknowledged to recommend PA, whereas few would recommend psychosocial or mind-body interventions. Barriers to recommend interventions to manage CRF included: lack of knowledge about CRF and its treatment, lack of time and complexity of the referral due to their accessibility and cost. CONCLUSION: In a diverse sample of HCPs, most acknowledged not to address CRF proactively with their patients, but identified several actionable barriers. Specific training on screening and management of CRF and improving the referral network dedicated to interventions need to be implemented.

Association of body mass index and cardiotoxicity related to anthracyclines and trastuzumab in early breast cancer: French CANTO cohort study.

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.