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.
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.
In BC patients, obesity appears to be associated with an important increase in risk-related cardiotoxicity (CANTO, ClinicalTrials.gov registry ID: NCT01993498).
ClinicalTrials.gov NCT01993498.
We assessed long-term associations of Granulocyte-Colony Stimulating Factors (G-CSF) use with patient-reported outcomes (PROs) and hematologic toxicity among chemotherapy-treated, early-stage breast ...cancer patients in CANTO (NCT01993498).
Among 2920 patients longitudinally followed-up until year-4 after diagnosis, 49% used G-CSF. In multivariable-adjusted mixed-models, EORTC QLQ-C30 pain and summary score were not substantially different between groups (overall adjusted mean difference, use vs no-use 95%CI: +1.27 -0.33 to +2.87 and −1.01 -1.98 to −0.04, respectively). PROs were slightly worse at year-4 among patients receiving G-CSF, although differences were of trivial clinical significance. No major differences were observed in leukocyte or platelet count over time.
•Studies on long-term side effects of G-CSF, including on quality of life, are lacking.•We evaluated PROs and hematological values until year-4 after diagnosis among women with early breast cancer receiving G-CSF.•49% women treated with adjuvant chemotherapy in CANTO (N = 2920) used G-CSF.•Long-term PROs and hematological values were not substantially different in women using G-CSF or not.•There were slightly worse outcomes at year-4 in patients using G-CSF, although of trivial clinical significance.
Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and ...quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology.
Patients (N = 220) with stage I-III breast cancer and BMI ≥ 25 kg/m
, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500-1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225-300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40.
MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care.
ClinicalTrials.gov NCT04304924.
Despite proven survival benefits after breast cancer, long-trem compliance with adjuvant hormone therapy remains a major issue, partly due to the side effects of treatment. In young women treated for ...breast cancer, these treatments include tamoxifen, anti-aromatase and LH-RH analogues, with even more side effects when these treatments are combined, especially for younger patients with more aggressive disease. The management of the potential side effects requires first of all detailed and precise information at initiation of treatment, and preventive measures including patient education. Once the treatment has been initiated, clinicians should be able to propose to their patients appropriate measures to alleviate the potential of the side effects, which can be of various types: biological (dyslipidemia), physical (weight gain, hot flushes, vaginal dryness, sexual disorders with low libido, musculoskeletal symptoms…) or psychosocial (anxio-depressive disorders, poor body image, difficulties of professional reintegration). Management of these effects can combine various modalities: drugs (switching hormone therapy, anti-depressants, hormonal treatments of vaginal dryness in some cases, gabapentin), physical treatments (CO2 laser for vulvovaginal atrophy) or psycho-physical techniques (physical activity, mindfulness, acupuncture…). Eventually, the lenghth of these adjuvant hormonal treatments requires supportive measures to help young patients engage in new lifestyle measures, in particular in term of physical activity and diet. This will help them mitigate the symptoms related to these side-effects while reducing the long-term risks related to their disease and treatments.
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.
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.
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
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
no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR
no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR
no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR
no, 2.29; 95% CI, 1.34 to 3.91).
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.
Nonadherence to long-term treatments is often under-recognized by physicians and there is no gold standard for its assessment. In breast cancer, nonadherence to tamoxifen therapy after surgery ...constitutes a major obstacle to optimal outcomes. We sought to evaluate the rate of biochemical nonadherence to adjuvant tamoxifen using serum assessment and to examine its effects on short-term, distant disease-free survival (DDFS).
We studied 1,177 premenopausal women enrolled in a large prospective study (CANTO/NCT01993498). Definition of biochemical nonadherence was based on a tamoxifen serum level < 60 ng/mL, assessed 1 year after prescription. Self-reported nonadherence to tamoxifen therapy was collected at the same time through semistructured interviews. Survival analyses were conducted using an inverse probability weighted Cox proportional hazards model, using a propensity score based on age, staging, surgery, chemotherapy, and center size.
Serum assessment of tamoxifen identified 16.0% of patients (n = 188) below the set adherence threshold. Patient-reported rate of nonadherence was lower (12.3%). Of 188 patients who did not adhere to the tamoxifen prescription, 55% self-reported adherence to tamoxifen. After a median follow-up of 24.2 months since tamoxifen serum assessment, patients who were biochemically nonadherent had significantly shorter DDFS (for distant recurrence or death, adjusted hazard ratio, 2.31; 95% CI, 1.05 to 5.06;
= .036), with 89.5% of patients alive without distant recurrence at 3 years in the nonadherent cohort versus 95.4% in the adherent cohort.
Therapeutic drug monitoring may be a useful method to promptly identify patients who do not take adjuvant tamoxifen as prescribed and are at risk for poorer outcomes. Targeted interventions facilitating patient adherence are needed and have the potential to improve short-term breast cancer outcomes.
Adjuvant endocrine therapy is highly effective and appropriate for all breast cancer patients with hormone receptor positive tumors, pre and post menopausal women. It's an oral daily pill for many ...years, after primary treatment. Although this medication dramatically reduces reccurrence rates and risk of death, many breast cancer survivors either fail to take pills with prescribed frequency (adherence) or discontinue therapy (persistence) or even never begin to take it. It's difficult to know exactly the prevalence of adherence and persistence but women age younger than 40 years had the highest risk of discontinuation. Medical literature of the last 15 years in this area has been carefully reviewed considering initiation treatment background, specificity of premenopausal young women population, healthcare provider and patient communication and respective views. It's highlighted that dedicated care, at first and after in follow up, is an essential part for better adherence. Guidelines processing are more and more complicated, expert medical assesment is required, shared decision must be provide. Patients need enhanced knowledge about mode of action, benefits but also potential side effects, and optimized patient provider relationship for empathy and better comprehension. Providers must believe in treatment relevance and convey their convictions.
Regular physical activity is associated with improved symptom control in patients with breast cancer but its association with chemotherapy completion or response is unclear.
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.
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.
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.
NCT01993498.
Breast cancer of young women has medico-psychological issues, particularly in the perspective of "after cancer" period. The objective of the study was to analyze the changes in management, in a ...decade including the publication of Cancer Plans I and II.
This retrospective unicentric study involved two populations of women aged 40 and treated at the "Institut de cancérologie de Lorraine" in 2002-2004 (P1) and 2012-2014 (P2). Epidemiological-demographic, histological, diagnostic and therapeutic sequences were analyzed.
216 patients were included. The mean age was 35.7 years (range 22-40), with no significant epidemiological difference, except for an increased rate of obesity in P2. Preoperative biopsies became almost systematic and the pre-therapeutic care plan rate increased over the decade from 3.8% to 8% (p < 0.001). The rate of breast-conserving treatment remained stable. The sentinel lymph node rate increased from 4.4% in P1 to 31.9% in P2 (p < 0.001), while the rate of lymph node dissection decreased (p < 0.001) between the two periods. Resort to breast nurses, psycho-oncologists, fertility experts and oncogenetic consultations has also increased.
There is an improvement in the care and management of young women under 40 because of the first Cancer Plans. A study about the impact on the prognosis and a reflection to improve the experience of illness for these women are to lead.
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