ONC: Chemotherapy (2007)


Harvie MN, Campbell IT, Baildam A, Howell A. Energy balance in early breast cancer patients receiving adjuvant chemotherapy. Breast Cancer Research and Treatment. 2004;83:201-210.

Study Design:
Time Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To determine the reasons for weight gain in women with early breast cancer receiving adjuvant chemotherapy by assessing changes in body composition and energy balance (REE, physical activity, energy intake) during chemotherapy and in the 6 months after chemotherapy.
Inclusion Criteria:
  • Women with newly diagnosed invasive breast cancer
  • Breast surgery (mastectomy or wide local excision)
  • No endocrine abnormalities (diabetes mellitus, hyper/hypothyroidism)
  • No psychiatric morbidity
Exclusion Criteria:
Not discussed
Description of Study Protocol:


  • Over the course of a year, 44 patients were recruited by telephone within 3 weeks of breast surgery (mastectomy or wide local excision) and immediately prior to commencing adjuvant chemotherapy. 
  • Subjects were assigned to groups depending on their desire to undergo metabolic measurements.


Design Time series, concurrent comparison group


 Blinding used  None



  • Medical intervention
    • All women received adjuvant chemotherapy following mastectomy or wide local excision
    • Those undergoing wide excision also received 3 weeks of radiotherapy following chemotherapy
    • Chemotherapy regimens
      • 5-FU, epirubicin, cyclophosphamide: 6 x 28 day cycles
      • Cyclophosphamide, methotrexate, 5-FU: 6 x 28 day cycles
    • Ondansetron was used as an antiemetic rather than the usual 2-3 days of steroids
  • Groups
    • Non-monitored control group
      • No metabolic testing performed
      • Weight change over the year was documented to control for the intensive metabolic monitoring in the intervention group which might depress energy intake and attenuate weight gain.
    • Study group
      • Assessed every 3 months throughout the year from the commencement of chemotherapy
      • Measurements included:
        • anthropometry, body mass and composition determination
        • Total body potassium
        • Bioelectrical impedance
        • Energy (dietary) intake assessment
        • Energy expenditure
        • Physical activity assessment
    • Healthy volunteers
      • 21 women matched for age (± 2 yr) and weight (± 5 kg) were recruited from hospital staff as controls for the REE measurement
  • Nutrition education
    • No nutritional counseling was given other than general healthy eating advice.


Statistical Analysis

  • The independent t-test was used to compare change in weight over the year between adjuvant patients in the study and in the non-monitored control group.
  • REE in adjuvant patients was compared with 21 healthy women matched for age and weight using the independent t-test.
  • Significance was accepted at 0.05 level of probability.
  • Changes over time in the adjuvant group were determined from paired t-tests between baseline and the end of chemotherapy, and baseline and 1 year. Bonferroni adjustments were made to allow for the multiple testing.
  • No statistical analyses were performed on measurements taken at mid chemotherapy and 3 months postchemotherapy.


Data Collection Summary:

Timing of Measurements

  Baseline Prior to 3rd chemotherapy cycle 1 mo after final chemotherapy 9 mo from start of chemotherapy 12 mo from start of chemotherapy
Height x        
Weight x x x x x
BMI x x x x x
Waist circumference x x x x x
Hip circumference x x x x x
Skinfolds x x x x x
Total body potassium x x     x
Bioelectric impedance x x x x x
Dietary intake x x x x x
REE x x x x x
Physical activity x x x x x

 Also at baseline:

  • Weight change over the 6 months prior to diagnosis of breast cancer and weight change from diagnosis, were estimated from recalled weights.

Dependent Variables

  • Primary
    • Weight
      • Measured using a beam balance/stadiometer to the nearest 0.1 kg
    • Total body fat
      • Determined from body weight and skin fold measurements using the equations by Durnin and Womersly.
      • Skinfolds were measured at the biceps, triceps, subscapular, supra-iliac and abdominal sites with Harpenden calipers by a single investigator. Each measurement was repeated 3 times and the mean value was calculated.
      • Coefficient of variation for the determination of fat by skinfold measurements on different occasions was 1.1%.
    • Fat free mass (FFM)
      • Determined from body weight and skin fold measurements using the equations by Durnin and Womersly.
      • Coefficient of variation for the determination of FFM by skinfold measurements on different occasions was 0.08%.
    • Waist circumference
      • Measured by a single investigator with a tape measure to the nearest 1.0 mm.
    • Hip circumference
      • Measured by a single investigator with a tape measure to the nearest 1.0 mm.
    • Abdominal skinfold (see measurement description under total body fat)
    • REE
      • Determined by indirect calorimetry using a calibrated open circuit ventilated hood system (Deltatrac Metabolic Monitor MBM 100).
      • Manufactured maintained the instrument and periodic alcohol burns gave results all within 1% of predicted.
      • Measured under controlled conditions: following an overnight fast; abstention from caffeine for previous 12 hr, smoking for previous 24 hr; measurements were made a minimum of 15 min once steady state was reached; energy expenditure calculated with Weir equatio
    • Energy intake
      • Determined from 4 day weighed diaries completed before each assessment, in the week prior to the next chemotherapy cycle to avoid the acute effects of the treatment on dietary intake.
      • Records were reviewed with subjects to check for completeness and to determine unspecified portion sizes
    • Physical activity index (PAI)
      • During the week prior to each assessment, physical activity was quantified using the self-reported patient questionnaire of the Framingham study with records the numbers of hours spent asleep, at rest, work, and leisure.
      • Clarified questionnaire with subject and checked for completeness at each visit.
      • Hours at each level of activity were weighted by relative enrgy expenditure for activities and were summed to give a PAI.
  • Secondary
    • Bioelectrical impedance
      • Measure of total body water, FFM and fat mass
      • Measurement conditions: apyrexial, fasted for 12 hr, and supine for 10 min prior to measurement
    • Total body potassium (TBK)
      • Measure of lean body mass
      • Relative changes in 40K were determined.
      • Sensitivity of the detectors and instrumental stability were determined after each measurement by performing a static count of potassium standard.
      • The measured values were corrected for changes in sensitivity of the scanner and any change in body size of the patient between measurements using a correction factor.
      • Precision of the measurement was 2% (coefficient of variation).


Independent Variables


Control Variables


Description of Actual Data Sample:


Initial N:

  • Study group: 21
  • Non-monitored controls: 23  

Attrition (final N):

  • Study group: 17
    • 3 withdrew because of work and family commitments
    • 1 developed metastatic disease and die
  • Non-monitored controls: 21
    • 1 developed metastatic disease and withdrew
    • 1 received follow up at a different hospital

Subject Characteristeristics


Study Group (N=17)

Controls (N=21)
Age (yr) 46.1 (9.5)* 45.0 (7.4)*
Smoker 21% 27%
Premenopausal 76% 86%
Chemotherapy induced menopause 70% 63%
Change in wt in the 2-4 wks since diagnosis (kg)





Change in wt in the 6 months prior to diagnosis





Weight (kg) 70.3 (11.3)* 67.0 (12.2)*
Height (m) 1.60 (0.07)* 1.62 (0.08)*
BMI 27.1 (4.1)* 25.3 (3.7)*

Tumor size <5 cm:>5 cm

16:1 19.3
WLE:mastectomy 9:8 14:8
grade of tumor 2:3 7:10 8:14
Chemotherapy regimen

12 FECb

15 FEC
  5 CMFa 7 CMF

* Mean (SD)

** Median (range)

aCMF 6 x 28 day cycles; CMF administered day 1 and 8 of each cycle

bFEC 6 x 28 day cycles; FEC administered day 1, F & C only administered day 8

C=cyclophosphamide; M=methotrexate; F=fluouracil; E=epirubicin

WLE=wide local excision

Age: see table

Ethnicity: not discussed

Other relevant demographics: see table

Anthropometrics see table

Location: South Manchester University Hospitals NHS Trust, Manchester, UK



Summary of Results:



Study Group

Mean ± SD

Non-Monitored Control group

Mean ± SD

Statistical Significance of Group Difference

Weight change over the year (kg)




  1.  Refutes a priori hypothesis that intensive metabolic investigations would limit weight gain in the study group.

Prechemotherapy and change in body mass and indices of body composition over the year in women receiving adjuvant chemotherapy



Mean (SD)

Immediately Postchemotherapy

Mean (95% CI)

1 year

Mean (95% CI

Weight (kg) 70.3 (11.3) 3.3 (1.4-5.3)* 5.0 (3.0-6.9)**
Body fat (%) 35.9 (5.8) 3.6 (2.2-4.9)** 6.2 (4.9-7.4)**
Total fat (kg) 25.8 (7.6) 4.0 (2.3-5.8)** 7.1 (4.8-9.5)**
FFM (kg) 44.5 (4.6) -0.5 (-1.6-0.6) -1.7 (-0.4 to -3.0)*
Total body K counts 908 (114) 47 (-12-111) 108 (21-196)
Bioelectrical impedance 567 (61) -14 (-32 to -3)

-27 (-8 to -47)

Abdominal skinfold (mm) 38.0 (15) 11 (6-17)** 16 (11-22)**
Waist (cm) 84.8 (10.5) 3.5 (1.4-5.6)* 5.1 (2.8-7.4)**
Hip (cm) 104.8 (8.7) 2.9 (-0.7-5.0) 3.8 (1.1-6.5)

*Significant differences from prechemotherapy; P<0.05 with Bonferroni adjustment

**Significant differences from prechemotherapy; P<0.01 with Bonferroni adjustment

  1. Weight increased 3.3 kg from baseline weight during adjuvant chemotherapy (P<0.05) and continued to increase in the 6 months postchemotherapy so that at 1 year subjects had gained 5.0 kg from baseline (P<0.001).
  2. There was a significant increased in body fat during adjuvant chemotherapy (4.0 kg; P<0.01) and in the 6 months postchemotherapy so that at 1 year subjects had gained 7.1 kg of body fat (P<0.01).
  3. Abdominal fat stores continued to increase in the postchemotherapy period so that at 1 year subjects had experienced significant increased in both waist (5.1 cm; P<0.01) and abdominal skinfold (16 mm; P<0.01).
  4. There appeared to be an increase in hip circumference both during and in the 6 months postadjuvant treatment, but these changes were not statistically significant.
  5. There was not significant change in FFM (determined from skinfolds) over the course of chemotherapy (P=0.89), but there was a decline in FFM in the 6 months posttreatment; 1.72±2.5 (P<0.05).
  6. There was no significant change in total body potassium over the course of chemotherapy (P=0.93) or in the 6 months posttreatment (P=0.34)
  7. There was no consistent pattern of change of impedance over the study. None of the changes were statistically significant.


Prechemotherapy and change in energy balance over the year in women receiving adjuvant chemotherapy



Mean (SD)

Immediately Post-chemotherapy

Mean (95% CI)

1 year

Mean (95% CI)

REE (kJ)  5893 (504)


-363 to -60



REE/kg FFM (kJ/kg)  134.0 (13.7) -1.8 (-7.2-3.5)



Energy intake (kJ)  8091 (1628)





PAI  30.7 (2.6)





Energy cost of physical activity (kJ)  1606 (844)





 *Significant differences from prechemotherapy P<0.05 with Bonferroni adjustment

  1. Subjects who were to receive adjuvant chemotherapy had a significantly greater REE than the healthy age and weight matched control subjects. Mean (SD) REE in the adjuvant group was 100.5±8.0% Harris Benedict compared to 94.5±8.4% Harris Benedict in the 21 age and weight matched volunteers (P=0.05).
  2. REE was 151 kJ lower at the end of chemotherapy (p<0.05) and returned to prechemotherapy values at 1 year (P=0.94).
  3. There was no difference in REE/kg FFM at the end of chemotherapy (p=0.49) or at 1 year (P=0.15).
  4. There appeared to be a decrease in energy intake at 1 year (P=0.3).
  5. The PAI appeared to be lower by the end of chemotherapy (P=0.47) and to increase by the end fo the year (P=0.23).
  6. The energy cost of physical activity appeared to decrease at the end of chemotherapy (P=0.58), but was significantly higher at the end of the year (P<0.05). The increase at 1 year was a function of a slight increase in activity level from baseline, but mainly reflected the increased energy cost of exercise at the higher body weight.

Other Findings


Author Conclusion:
Treatment with adjuvant chemotherapy causes gain of body fat because of reduced energy expenditure, and the failure of women to reduce thier energy intake to compensate for the decline in energy requirement during and in the 6 months posttreatment.
Funding Source:
Scientific Hospital Supplies
Reviewer Comments:

Whether subjects entered the study or non-monitored control groups depended largely on proximity to the hospital and the ability to attend regularly. Are the groups comparable?

Investigators didn't discuss how weight measurements were obtained throughout the year for the non-monitored control group.

Small sample size with no sample size calculation.

This study mainly compared changes in the adjuvant chemotherapy group before chemotherapy and during the first year. The other groups (non-monitored control group and the healthy volunteers) played a limited role in the study.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? No
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes