Changes in body composition as a result of chemotherapy : Comparing women with and without breast cancer

Because of the improved survival rate, both short term and long term adverse effects of breast cancer treatment have become increasingly important. Body weight and body composition before, during, and after chemotherapy may influence side effects during treatment and survival. The aims of this thesis were to assess among stage I-IIIB breast cancer patients: 1) the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy, 2) potential changes in body weight and body composition during and after chemotherapy compared to changes in age-matched women without cancer in the same time period, and 3) dietary intake during chemotherapy compared to age-matched women without cancer in the same time period. Chapter 2 describes the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy. Data from 172 breast cancer patients who participated in the COBRA-study were analysed. Body composition was measured using a total body Dual Energy X-ray Absorption (DEXA) scan. Information regarding dose-limiting toxicities was abstracted from medical records. A higher BMI (kg/m2) and a higher fat mass (kg and percentage) were associated with an increased risk of dose-limiting toxicity, while lean body mass (kg) was not associated with risk of toxicities. Chapter 3 presents the findings of a meta-analysis on changes in body weight during chemotherapy in breast cancer patients. The meta-analysis showed an overall gain in body weight of 2.7 kg (95% CI: 2.0-3.3) during chemotherapy, with a high degree of heterogeneity (I2= 94.2%). Weight gain in breast cancer patients was more pronounced in papers published before 2000 and studies including cyclophosphamide, methotrexate and 5-fluorouracil as chemotherapy regime. Chapter 4 describes changes in body weight and body composition during and after chemotherapy. Data from 145 patients and 121 women of an age-matched comparison group, participating in the COBRA-study were analysed. Body composition was measured using DEXA-scan at three time points during the study period. For the patient group, these tie points were: before start of chemotherapy, shortly after chemotherapy, and 6 months after chemotherapy. For the comparison group these measurements were conducted over a similar time frame: baseline, 6 months after baseline, and 12 months after baseline. In addition, we identified determinants of changes in body weight and body composition. Shortly after chemotherapy, patients had a significantly higher body weight, BMI, and lean body mass than women in the comparison group, while fat mass was similar. Six months after chemotherapy no differences in body weight or body composition were observed between the patient and comparison group. A younger age, better appetite during chemotherapy, and an ER-receptor negative tumour were associated with greater changes in body weight over time. A younger age and better appetite during chemotherapy were associated with greater changes in fat mass over time, while the only determinant associated with greater changes in lean body mass over time was a better appetite during chemotherapy. Chapter 5 describes the dietary intake and food groups before and during chemotherapy of breast cancer patients compared with women without cancer. In addition we assessed the association between symptoms and energy intake. Data from 117 breast cancer patients and 88 women without breast cancer who participated in the COBRA-study were used. Habitual dietary intake before chemotherapy was assessed using a food frequency questionnaire. Two 24-hr dietary recalls were used to assess actual dietary intake during chemotherapy for patients and within 6 months for the comparison group. Shortly after the 24-hr dietary recall, participants filled out questionnaires about symptoms. Before chemotherapy, dietary intake was similar for both groups. During chemotherapy, breast cancer patients reported significantly lower total energy, total fat, total protein, and alcohol intake than women without cancer, which could be explained by a lower intake of specific food groups. Overall results from this thesis suggest that pre-treatment fat mass is associated with dose-limiting toxicities during chemotherapy. Weight gain during chemotherapy appeared to be more modest than we expected based on literature and changes in body composition during chemotherapy consist mainly of an increase in lean body mass, which is only temporary and returned to baseline within 6 months after chemotherapy. A higher appetite during chemotherapy was associated with changes in body weight and body composition. A younger age at diagnosis was associated with greater changes in body weight and fat mass, but not with changes in lean body mass. In addition, an ER-receptor negative tumour was associated with greater changes in body weight, but not with changes in fat mass or lean body mass. During chemotherapy women with breast cancer have a lower intake of energy, fat, protein and alcohol compared to age-matched women without cancer, which was expressed in a lower intake of specific food groups. The results of this thesis do not suggest that dietary intake is associated with weight gain during chemotherapy.</p

Exploring changes in dietary intake, physical activity and body weight during chemotherapy in women with breast cancer : A Mixed-Methods Study

Background: The present study aimed (i) to assess changes in dietary intake (DI), physical activity (PA) and body weight (BW) in breast cancer patients during chemotherapy; (ii) to describe how women explained, experienced and dealt with these potential changes; and (iii) to eventually develop lifestyle intervention strategies tailored to the women's personal needs during chemotherapy. Methods: A longitudinal parallel mixed-method design was used with quantitative assessment of changes in dietary intake (24-h recall, Appetite, Hunger, Sensory Perception questionnaire), physical activity (Short Questionnaire to Assess Health-enhancing physical activity, Multidimensional Fatigue Inventory) and BW (dual-energy X-ray absorptiometry), in addition to qualitative interviews with 25 women about these potential changes during chemotherapy. Results: Most women who perceived eating less healthily with low energy intake (EI) and being less active before diagnosis continued to do so during chemotherapy, according to quantitative measurements. They struggled to maintain sufficient energy intake. Despite a lower than average reported EI, they unexpectedly gained weight and explained that fatigue made them even more inactive during chemotherapy. Active women usually managed to stay active because exercise was very important to them and made them feel good, although they also suffered from the side-effects of chemotherapy. They found more ways to deal with taste, smell and appetite problems than women with a lower energy intake. Conclusions: The combination of the quantitative and qualitative data provided more insight into the changes in dietary intake, physical activity and BW during chemotherapy. The women's explanations showed why some women remain active and others need support to deal with changes in lifestyle factors such as healthy nutrition and fatigue.</p

Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy

Cancer treatments, toxicities and their effects on lifestyle, may impact levels of vitamin D. The aim of this study was to determine serum 25-hydroxyvitamin D3 (25(OH)D3) levels before, directly after and 6 months after chemotherapy in breast cancer patients (n = 95), and a comparison group of women (n = 52) not diagnosed with cancer. Changes in 25(OH)D3 levels over time were compared using linear mixed models adjusted for age and season of blood sampling. Before start of chemotherapy, 25(OH)D3 levels were lower in patients (estimated marginal mean 55.8 nmol/L, 95% confidence interval (95%CI) 51.2–60.4) compared to the comparison group (67.2 nmol/L, 95%CI 61.1–73.3, P = 0.003). Directly after chemotherapy, 25(OH)D3 levels were slightly decreased (–5.1 nmol/L, 95%CI –10.7–0.5, P = 0.082), but ended up higher 6 months after chemotherapy (10.9 nmol/L, 95%CI 5.5–16.4, P 3 levels remained stable throughout the study. Use of dietary supplements did not explain recovery of 25(OH)D3 levels after chemotherapy. We reported lower 25(OH)D3 levels in breast cancer patients, which decreased during chemotherapy, but recovered to levels observed in women without cancer within 6 months after chemotherapy. Suboptimal 25(OH)D3 levels in the majority of the participants highlight the relevance of monitoring in this vulnerable population.</p

Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I–IIIB breast cancer receiving chemotherapy

Purpose: Initial dose of chemotherapy is planned based on body surface area, which does not take body composition into account. We studied the association between fat mass (kg and relative to total body weight) as well as lean mass (kg and relative to total body weight) and toxicity-induced modifications of treatment in breast cancer patients receiving chemotherapy. Methods: In an observational study among 172 breast cancer patients (stage I–IIIB) in the Netherlands, we assessed body composition using dual-energy X-ray scans. Information on toxicity-induced modifications of treatment, defined as dose reductions, cycle delays, regimen switches, or premature termination of chemotherapy, was abstracted from medical records. Adjusted hazard ratios and 95% confidence intervals (95% CI) were calculated to assess associations between body composition and the risk of toxicity-induced modifications of treatment. Results: In total, 95 out of 172 (55%) patients experienced toxicity-induced modifications of treatment. Higher absolute and relative fat mass were associated with higher risk of these modifications (HR 1.14 per 5 kg; 95% CI 1.04–1.25 and HR 1.21 per 5%; 95% CI 1.05–1.38, respectively). A higher relative lean mass was associated with a lower risk of modifications (HR 0.83 per 5%; 95% CI 0.72–0.96). There was no association between absolute lean mass and risk of toxicity-induced modifications of treatment. Conclusions: A higher absolute and a higher relative fat mass was associated with an increased risk of toxicity-induced modifications of treatment. Absolute lean mass was not associated with risk of these treatment modifications, while higher relative lean mass associated with lower risk of modifications. These data suggest that total fat mass importantly determines the risk of toxicities during chemotherapy in breast cancer patients.</p