Breast cancer is the most prevalent cancer in American women with 246,660 new cases and 40,890 deaths projected in 2016 (30). Despite the improved 5-yr survival rate in the past several years, breast cancer survivors (BCS) struggle with adverse side effects as a result of cancer and its treatment (24). Cancer therapy negatively affects body composition by decreasing lean mass (LM) and increasing fat mass (FM) (10). These alterations in body composition may lead to phenotypes known as sarcopenia (low muscle/LM) and sarcopenic obesity (combined sarcopenia with excess body weight). These conditions will ultimately have a negative effect on the quality of life and physical function of BCS (33). In a study of 471 women with stages I–III breast cancer, sarcopenia was evident in 16% of the women, and was an independent predictor of shorter survival (25,36). Therefore, implementing appropriate interventions to counteract the loss of LM and the gain of FM in BCS is imperative. Moreover, interventions that increase LM could potentially increase the basal metabolic rate of the BCS and offset the gains in FM. Two intervention programs that may be promising for BCS include resistance training (RT) and protein supplementation.
Intervention programs using RT at intensities between 60% and 100% of one-repetition maximum (1-RM) have been shown to increase LM and strength in healthy adults (6,12). Although RT interventions in BCS posttreatment have shown improvements in muscular strength (31,39), only one has reported a significant accretion of LM (29), whereas other studies have found maintenances in LM (19,39). These different findings may be due to the differences in exercise volumes and intensities. Exercise intensity is a determining factor for providing a stimulus sufficient enough to illicit changes in LM in healthy adults and perhaps BCS. However, higher intensities may not be possible for the BCS because clinical practice in the past has advised BCS with or at risk of developing lymphedema to refrain from lifting heavy objects with the upper body limbs on the same side affected by breast cancer, believing that this weight would exacerbate the lymphedema. However, evidence suggests the contrary, as moderate-intensity exercise has been shown not to cause or exacerbate lymphedema (1). Another stimulus, in addition to RT, for accretion of LM in BCS may be the addition of amino acids as protein supplementation has been beneficial in increasing LM in aging adults (8).
Healthy aging adults have a blunted postabsorptive muscle protein synthetic rate in response to amino acid feeding (14,17). Recently, it has been recommended that older adults increase protein intake from the recommended daily allowance of 0.8 to 1.4–1.6 g·kg−1·d−1 (7). In a randomized, double-blind, placebo-controlled study with two groups, increasing protein intake in frail elderly adults (78 ± 1 yr) using a 15-g protein supplement twice a day in combination with RT increased LM (+1.3 ± 0.4 kg; P = 0.006) compared with the group consuming a placebo (34). Thus, a combined RT and protein supplementation intervention may provide the necessary stimulus to increase LM in BCS.
Therefore, the purpose of the present study was to examine the effects of RT or RT and protein supplementation (RT + protein) on muscular strength, body composition (LM and FM), and biomarkers of muscle and fat metabolism and inflammation in postmenopausal BCS. We hypothesized that BCS participating in RT + protein will demonstrate greater improvements in strength and body composition, blood biomarkers of muscle (insulin-like growth factor 1 [IGF-1]), and fat (adiponectin) metabolism and decreases in the biomarker of inflammation, human C-reactive protein (CRP), compared with BCS participating in only RT.
Female BCS were recruited by flyers posted in cancer centers, radio announcements, through the local newspaper, health fairs, and word of mouth. A total of 57 BCS called to inquire about the study. Of these, 10 declined to participate and 13 did not meet the eligibility requirements as outlined in Figure 1. Therefore, 33 postmenopausal BCS (stages 0–III), ages 40–75 yr, having completed treatment (at least 2 months posttreatment) were assigned into one of the two intervention groups: 1) RT or 2) RT + protein. Women currently taking hormone suppressant therapies were eligible to participate. The rationale for accepting women currently taking hormone suppressant therapies was these therapies are often prescribed for 5 to 10 yr after initial treatments are completed in estrogen receptor positive breast cancer. Thus, the exclusion of these BCS would have significantly reduced the number of women that would be eligible. Women diagnosed with active or stage IV breast cancer, uncontrolled hypertension (≥160/100 mm Hg), uncontrolled diabetes (blood glucose >250 mg·dL−1), allergies to milk protein, participating in a regular exercise program (RT >1 d·wk−1 or aerobic exercise >2 d·wk−1), and/or taking pharmacological doses of vitamin D (≥6000 IU·d−1) were not eligible to participate. Pharmacological doses of vitamin D are equivalent to approximately greater than 6000 IU daily or 50,000 IU once per week (15). The Florida State University Human Subjects Institutional Review Board approved this study. Written informed participant and physician's consents and medical histories were completed before participation.
Participants were scheduled for two baseline visits separated by 1 wk. All baseline measurements were repeated at the end of the 12-wk intervention. Posttesting was completed 36–48 h after the final RT session and within 24–48 h after consuming the last serving of the protein supplement.
Blood collection and analysis
Before all laboratory testing, the participants were asked to refrain from alcohol and exercise for 24 h. During the first visit, participants came to the laboratory during the hours of 0600 and 1000 after an overnight fast (>8 h). Venous blood samples (20 mL) were collected from the antecubital space to measure IGF-1, adiponectin, and CRP. All blood samples were analyzed at the conclusion of the study using commercially available ELISA kits according to the manufacturer's instructions (R&D Systems®). All assays were run in duplicate, and the intra-assay coefficients of variation (CV) for IGF-1, adiponectin, and CRP were 10.8%, 4.6%, and 2.8%, respectively. Only samples with a CV less than 20% were analyzed. The interassay CV for IGF-1, adiponectin, and CRP were 15.7%, 6.7% and 3.3%, respectively.
Anthropometrics and body composition
After the blood draw, height (m) and weight (kg) were assessed using a wall-mounted stadiometer and digital scale (Seca Corporation, Hanover, MD) to calculate body mass index. Waist circumference was measured a minimum of two times and averaged if measurements were within 5 mm using a Gulick fiberglass measuring tape with a tension handle (Creative Health Products, Inc.; Ann Arbor, MI). Body composition was assessed via dual-energy x-ray absorptiometry (model DPX-IQ; GE Healthcare Inc., Madison, WI) to measure total body LM, FM, LM to FM ratio (LM/FM), and percent body fat. Testing and analyses were completed according to the manufacturer's instructions and specifications.
Handgrip (HG) strength was measured using an HG dynamometer (Creative Health Products, Inc., Ann Arbor, MI). Handgrip measurements were taken three times on each arm, and the highest measurements from each arm were added together. Upper and lower body strength measures were assessed using chest press and leg extension machines (MedXTM, Ocala, FL). After a warm-up, participants were progressed toward the maximum weight that they could lift one time (1-RM) through a full range of motion. All measurements were recorded, with the goal of achieving a 1-RM within 3 to 5 attempts.
The participants in both groups were asked to maintain their normal dietary habits for the duration of the study. Three-day food records (two weekdays and one weekend day) were assigned at baseline, 6, and 12 wk. All food records were analyzed at the end of the study (U.S. Department of Agriculture; choosemyplate.gov). Protein change, which is the change in habitual protein intake (g·kg−1·d−1) of each group, and protein spread, which is the percent difference in protein intake during the study between experimental (RT + protein) and control (RT) group, were determined according to the calculations of Bosse and Dixon (4) as follows:
Upon completion of baseline testing, each participant was stratified by age, LM, stage of cancer, and treatment as well as calcium and vitamin D intake to one of two intervention groups: 1) RT or 2) RT + protein. Both groups were given a pedometer and physical activity log at baseline to record daily number of steps for 1 wk (randomly selected) out of the first, second, and third month of the study. All participants were asked to maintain their normal calcium and vitamin D intake and to record their intake in log books. Participants in both groups who were not taking a minimum of the recommended dietary intake for calcium (1200 mg) and vitamin D (800 IU) were asked to take a daily calcium and vitamin D supplement (Member's Mark ™) that was provided to them for the duration of the study. The RT + protein group also consumed two servings of a blended whey and casein protein supplement daily (whey protein concentrate, milk protein isolate, whey protein isolate, micellar casein blend; 585.8 kJ, 1.0 g fat, 12.0 g carbohydrate, 20 g protein; Supreme Protein®, Dymatize Enterprises, LLC, Dallas, TX). The participants consumed the first 20 g of protein within 30 min of completing their RT on training days and in the morning before breakfast on nontraining days. They consumed the second 20 g of protein as the last meal within 30 min of going to bed on all days of the week. The rationale for choosing this moderate dose of protein is that it is well tolerated by participants on a daily basis and has been shown to positively influence body composition in nonmalignant overweight middle-age to older adults (2).
Training was completed under the supervision of exercise instructors on two nonconsecutive days each week. Exercise machines included the MedXTM chest press, leg press, leg extension, biceps curl, triceps press down, overhead military press, seated row, leg curl, abdominal crunch, and lower back extension. Exercises were performed in a superset design in which participants performed a set on an upper body machine followed by a set on a lower body machine until three sets on each machine were completed before continuing to the next pairing of upper and lower body exercises. Intensity began at 65% of 1-RM and progressed throughout the 12 wk. Weight on each exercise was increased at the beginning of each week based on the number of repetitions performed during the third set to fatigue on the last training session of the previous week. Thus, for every two repetitions performed past 10 repetitions in the third set, the weight was increased by 1.81 kg (4 lb). The weight was also increased by 1.81 kg if the participants were only able to complete 10 repetitions in the third set. The weight was maintained on the exercises where less than 10 repetitions were completed. The total training volume for the study was calculated by multiplying the weight lifted by the number of repetitions performed for each set for each week (weight lifted × repetitions × sets). The average training volumes for upper body (chest press, biceps curl, triceps press down, overhead military press, seated row, abdominal crunch, and lower back extension) and lower body (leg press, leg extension, and leg curl) exercises were calculated for weeks 1–6 and 7–12.
Descriptive statistics, mean, and SD were calculated for all variables. Dependent variables at baseline were analyzed by one-way ANOVA, and when group differences in baseline variables were observed, an ANCOVA was performed with the baseline variable as the covariate. A 2 × 2 (group–time) repeated-measures ANOVA was used to analyze variables of strength, body composition, and blood biomarkers. A 2 × 3 (group–time) repeated-measures ANOVA was used to analyze dietary intake. When interactions were significant, ANOVA were used to compare between group values. Effect sizes (ES; eta-squared) were also used to determine the meaningfulness of the significant findings. An intention-to-treat analysis was used to evaluate pre- and posttest scores to address the effects of the interventions on all randomized participants regardless of whether they completed the study or not. Using the principle of last observation carried forward, missing posttest scores was filled using the test scores that were collected closest to the time of dropout. All analyses were performed using the SPSS (version 21) statistical package (IBM®, Armonk, NY). All significance was accepted at P ≤ 0.05.
Baseline characteristics as well as breast cancer history are displayed in Table 1. There were no significant differences between groups in baseline measures of dependent variables except lower body strength. Thirty-two of the participants were Caucasian and one was African American. On the basis of physical activity levels, the participants were considered low active (35), with 33% (n = 11) being classified as overweight and 27% (n = 9) being classified as obese.
RT intensity, volume, and adherence
The overall exercise intensity began at 65% ± 2% and 64% ± 2% of each participant's baseline 1-RM for the chest press and leg extension machines. The total body and the lower body training volume were similar between the groups for the 12 wk; however, the training volume for the upper body exercises was slightly greater in RT + protein and was approaching a significant difference between the groups (F1,31 = 3.492, P = 0.071). Exercise intensity was not different between groups. The exercise adherence for all the participants in both groups including those who did not complete the intervention was 89.7% ± 19.7% and was not different between groups. Training and adherence data are presented in Table 2.
One participant in RT did not complete any of her 3-d dietary logs. Therefore, only 32 logs were analyzed (Table 3). All values in Table 3 for RT + protein include the total dietary intake as well as the two servings of the daily protein supplement (585.8 kJ, 1.0 g fat, 12.0 g carbohydrate, and 20 g protein).
Dietary recall: baseline to 12 wk
There were no significant group–time or time effects from baseline to 12 wk for changes in energy, carbohydrate, fat, protein, and protein by body weight intake. Only protein (P = 0.083) and protein by body weight (P = 0.056) intake were approaching significance for a group–time interaction from baseline to 12 wk within which the RT had a drop in protein of 1.5 ± 39.7 g·d−1, whereas RT + protein increased by 17.6 ± 12.3 g·d−1.
From baseline to 12 wk, there was a significant group–time interaction (F1,30 = 30.366, P < 0.001, ES = 0.50) for dietary calcium. Calcium intake significantly increased in RT + protein by 560.4 ± 366.5 mg·d−1, whereas RT decreased by 180.5 ± 406.8 mg·d−1. A significant group–time interaction (F1,30 = 13.317, P = 0.001, ES = 0.31) from baseline to 12 wk was also observed for dietary vitamin D with RT + protein increasing vitamin D intake by 289.4 ± 266.3 IU·d−1 compared with RT decreasing intake by 69.3 ± 299.4 IU·d−1.
Because the present study was the first to investigate the addition of a protein supplement to an RT intervention in BCS, we decided to explore the potential effect that the provision of a dietary supplement would have on the dietary habits of the BCS. To determine whether any variation in dietary habits occurred, we performed additional analyses of the dietary logs from baseline to 6 wk, and from 6 to 12 wk.
Dietary recall: baseline to 6 wk
Analyses of dietary logs reveal that from baseline to 6 wk, there were no group–time interactions for energy, carbohydrate, fat, protein, and protein by body weight (g·kg−1·d−1) intake between the two groups. Significant time effects were observed for changes from baseline to 6 wk as intake of energy (F1,30 = 4.593, P = 0.04, ES = 0.13), carbohydrate (F1,30 = 7.584, P = 0.01, ES = 0.20), and fat (F1,30 = 7.449, P = 0.011, ES = 0.20) decreased in both groups, whereas protein (F1,30 = 6.594, P = 0.015, ES = 0.18) and protein by body weight (F1,30 = 6.865, P = 0.014, ES = 0.19) increased in both groups. There was a significant group–time interaction (F1,30 = 8.075, P = 0.008, ES = 0.21) for dietary calcium intake (mg·d−1) from baseline to 6 wk with RT + protein increasing calcium intake by 425.8 ± 509.7 mg·d−1 compared with RT (+101.7 ± 556.4 mg·d−1). A significant group–time interaction (F1,30 = 8.598, P = 0.006, ES = 0.22) was observed for dietary vitamin D intake (IU·d−1) from baseline to 6 wk. Vitamin D intake significantly increased in RT + protein by 195.3 ± 243.2 IU·d−1, whereas RT decreased by 21.3 ± 165.1 IU·d−1.
Dietary recall: 6 to 12 wk
There were no significant group–time interactions or time effects in any of the dietary variables from 6 to 12 wk. RT nonsignificantly decreased protein intake by 8.3 ± 26.8 g·d−1, and the RT + protein nonsignificantly decreased their protein intake by 1.8 ± 23.9 g·d−1.
Dietary recall: protein change and spread
The protein change (change in habitual protein intake) of the RT + protein and RT was 27.3% ± 34.5% and 5.2% ± 45.3% and was not significantly different between the groups. The protein spread (percent difference in protein intake between the groups) at 12 wk was 29.4%. Adherence to the protein supplement was 91% ± 9%. The average adherence of calcium and vitamin D supplementation was significantly greater in the RT + protein compared with RT (94% ± 6% vs 84% ± 19%; F1,24 = 4.259, P ≤ 0.05).
Values of muscular strength and physical activity levels from baseline to 12 wk are presented in Table 4. One participant in the RT + protein was not able to successfully perform the baseline 1-RM leg extension because of pain in the anterior portion of her lower leg from peripheral neuropathy. Baseline leg extension strength was significantly greater in RT + Protein compared with the RT (F1,30 = 4.103, P = 0.052). Although this difference was detected at a significance of P = 0.052, to be conservative, we decided to perform an ANCOVA as we cannot say with certainty that the difference is not different because our power is not very high. When the baseline leg extension was normalized at 96.8 kg, there was no significant interaction in the adjusted means values at 12 wk (RT + protein, 118.6 ± 3.1, vs RT, 111.9 ± 3.1 kg; P = 0.480). There were no group–time interactions for chest press and HG strength. Significant time effects were observed for all measures of muscular strength with both groups increasing HG (F1,31 = 20.772, P < 0.001, ES = 0.40), chest press (F1,31 = 93.496, P < 0.001, ES = 0.75), and leg extension (F1,30 = 87.205, P < 0.001, ES = 0.74) for the 12 wk. There were no significant group–time or time effects observed in physical activity levels during the study.
Body composition measures are also presented in Table 4. There were no group–time interactions in measures of body composition. Significant time effects were observed for reductions in waist circumference (F1,31 = 17.436, P < 0.001, ES = 0.36). There were significant time effects observed for increases in total body LM (F1,31 = 27.416, P < 0.001, ES = 0.47) and LM/FM ratio (F1,31 = 17.856, P < 0.001, ES = 0.37) as well as for decreases in FM (F1,31 = 6.012, P ≤ 0.05, ES = 0.16) and total body fat percentage (F1,31 = 23.366, P < 0.001, ES = 0.43).
Table 5 presents the serum samples that were analyzed. One sample from IGF-1 had a CV of 28% and was excluded. Measurements of CRP for the RT + protein were significantly greater than RT, and these differences remained at 12 wk. There were no group–time interactions nor time effects in any of the blood biomarkers except a significant time effect observed in IGF-1 (F1,25 = 5.631, P = 0.019, ES = 0.18).
To our knowledge, this is the first study to include a protein supplement as part of an RT intervention for BCS and one of only two studies that have found significant increases in LM in BCS. The present study demonstrated that 12 wk of RT (2 d·wk−1) at moderate to high intensity (65%–81% 1-RM) significantly increased muscular strength, LM, and decreased FM in female BCS without increasing IGF-1 beyond normal ranges. The improvements in muscular strength in the present study are similar to other RT studies in BCS (32,38); however, the RT did not affect adiponectin and CRP. The protein supplementation did not have an added benefit; however, consumption of 40 g·d−1 of a whey and casein blend protein beverage was well tolerated and adhered to. The 40-g·d−1 of supplemental protein did not induce a change in any variable; however, based on food logs, reductions in total calories and dietary protein intake from whole foods resulted in only a net protein increase of 17 g·d−1 for RT + protein. Therefore, we reject our hypotheses that greater changes in muscular strength, body composition, and blood biomarkers would be seen in BCS who consumed a protein supplement combined with RT compared with BCS who only performed RT.
Previous studies (32,39) that have used RT to modulate LM and FM in BCS have found significant differences between the RT and the nonexercising control groups due to the control groups decreasing LM and RT groups maintaining or having slight increases in LM. Only one other study has found a significant increase in LM (29), and none has found significant decreases in FM. The present study observed significant changes over time, with the BCS increasing LM by 2% (+0.88 kg) and LM/FM ratio by 5% while decreasing FM by 2% (−0.51 kg) and body fat percentage by 1%. Similar to our findings, a 6-month RT intervention by Schmitz et al. (29) found LM to significantly increase by 0.88 ± 0.23 kg and body fat percentage to decrease (−1.15% ± 0.45%). It is important to note that the changes in the study by Schmitz et al. (29) occurred after 6 months of RT, whereas the improvements in body composition in the present study were observed after only 12 wk of RT performed twice a week. The training volume and intensity utilized in the present study used a superset design, and most importantly had the women perform their third set of each exercise to fatigue, thereby often exceeding the 12 repetitions used in previous studies (32,39) providing a greater stimulus for improvements in body composition (23). The RT sessions were well tolerated with an adherence rate of 90% and no reported injuries. The RT intervention did not elicit any adverse effects on arm swelling nor caused lymphedema in our BCS.
This is also one of the first studies to include a protein supplement as part of an intervention in BCS and thus provides direction for future studies. Initial analyses of baseline to 12-wk 3-d food logs revealed that by the end of the 12 wk, the BCS in RT + protein consumed a significantly greater amount of protein in their diet than RT as they increased from 1.00 ± 0.24 g·kg−1·d−1 (16% of total energy coming from protein) to 1.24 ± 0.30 g·kg−1·d−1 (21% of total energy coming from protein). The participants in RT maintained their protein intake from 0.99 ± 0.39 g·kg−1·d−1 (16% of total energy coming from protein) at baseline to 0.96 ± 0.41 g·kg−1·d−1 (17% of total energy coming from protein). However, changes in protein intake from baseline to 6 wk were not significantly different between the two groups, neither were changes from baseline to the average of the combined 6- and 12-wk food logs. Therefore, because of the variation in the 3-d logs at 6 and 12 wk, we cannot say for certain that RT + protein consumed significantly more protein than RT during the entire 12-wk intervention.
The protein supplement may have had some benefits for upper body strength, as the training volume of the upper body exercises was somewhat higher (P = 0.07) than RT. However, the absence of any group differences in changes in the measures of body composition between the RT + protein and the RT may be due to inadequate protein change and spread. Although the participants took the prescribed 40 g of added protein, they reduced their dietary protein so the net increase of 17 to 19 g·d−1 may not have created an adequate protein change to elicit a group–time effect. In their review, Bosse and Dixon (23) reported that an average protein change of at least +59.5% is needed to observe group differences in interventions using protein and RT. The protein change for the RT + protein group in the present study was only +27.3% ± 34.5% and, therefore, was probably not sufficient to stimulate an additional benefit of protein. Although the participants were asked to maintain their regular dietary intake throughout the study duration, the protein change of the participants in the RT + protein ranged from −2.8% to 143.1%. When an analysis for group differences was performed in changes in LM with only those participants in RT + protein who had a protein change greater than 20% (n = 8), a group–time effect that was approaching significance was observed (P = 0.079) for total body LM (RT + protein, +1.47 kg, vs RT, +0.68 kg; P = 0.079). Future studies need to standardize the diet of their participants or collect more frequent dietary logs to continuously ensure dietary habits are actually being maintained, and thus the protein beverage is indeed supplementing the diet of the experimental group. Bosse and Dixon (23) also reported that a protein spread of at least 66.1% has been observed in those studies that report group differences in LM between groups consuming and not consuming protein during RT interventions. The protein spread observed in the present study between the two groups was 29.4%. It is important to note that the studies reviewed by Bosse and Dixon to determine the recommendations for protein change and spread were in noncancer populations, and thus the requirements may be different for BCS. Because most studies are completed in healthy populations, more studies are needed to determine whether there is an optimal dose of protein needed to augment benefits in BCS. In addition, the absence of an effect of the protein supplement may be due to our decision to split the 40-g protein dose into two separate 20-g doses. As this was the first study to add a protein supplement to an exercise intervention for BCS, we were not sure whether a single dose of 40 g of the protein supplement would be well tolerated. Thus, we determined it prudent to split the dose into separate servings. Further, Tieland et al. (34) observed a significant treatment–time interaction for LM in older participants performing RT (twice a week, for 24 wk) and a protein supplement (30 g·d−1). The protein group consumed a 15-g protein supplement twice a day (15 g × 2) and had significant increases in LM (+1.3 kg) compared with a placebo (−0.3 kg). Thus, considering the anabolic resistance to amino acid feeding previously discussed, the present study chose to increase the protein dose moderately to 40 g·d−1, split into two 20-g servings. Our findings determined that 40 g of daily protein supplement, split into 20-g doses, was well tolerated by the BCS. Future studies should consider serving the 40-g in a single dose and possibly consider increasing the dose from 40 to 60 g to achieve an adequate protein change as discussed earlier. The decrease of 492 to 558 kJ·d−1 and 631 to 811 kJ·d−1 in energy intake in the RT + protein and RT groups, respectively, with only a net increase of 17–19 g·d−1 for RT + protein may have contributed to the lack of body composition differences between groups. It seems that it is the combination of the RT intervention and the caloric deficit that contributed to the decrements in FM, and the exercise intensity of the RT program that lead to the increases in LM that are not often observed in female BCS.
The BCS in both groups were asked to maintain their regular calcium and vitamin D intake throughout the study; however, there were significant group–time changes in dietary calcium and vitamin D intake. RT + protein increased average dietary calcium intake by +74% and vitamin D intake by +161% compared with a −20% and a −31% decrease in dietary calcium and vitamin D intake in RT. The group differences in dietary calcium and vitamin D intake is explained by the extra calcium (600 mg) and vitamin D (320 IU) provided by the daily protein supplement that was consumed by RT + protein. As there were no significant differences between the groups in any of the primary outcome variables, it is unlikely that the differences in calcium and vitamin D influenced these measures. It is also not clear what the role of calcium and vitamin D intake plays in muscle and fat metabolism during an RT intervention in BCS.
Contrary to our hypothesis, the women in RT + protein did not increase serum levels of IGF-1 and adiponectin, nor did they decrease levels of CRP to a greater extent than RT. IGF-1, a marker of muscle metabolism, increased significantly from baseline to 12 wk, thereby elucidating a potential mechanism for the increase in LM that IGF may be involved. However, the changes were small and other biomarkers and local signaling factors such as mechano-growth factor must be considered. Normal levels of IGF-1 range from 40 to 258 ng·mL−1 (3) and decrease with aging, which contributes to the loss of LM in older adults (21,28). As IGF-1 is a growth factor, a paradox exists as IGF-1 at levels above normal (40–258 ng·mL−1) can increase the development of estrogen-mediated breast carcinogenesis (18) via IGF-1's role in stimulating estrogen from adipose tissue. Thus, the concern for BCS is the risk of cancer reoccurrence by increasing IGF-1 levels to above normal levels of women 45 yr and older (11). The values of IGF-1 ranged from 46.9 to 202.5 ng·mL−1 by the end of the intervention. These findings are encouraging as they demonstrate that RT + protein of 40 g in BCS does not contribute to an increase in IGF-1 above healthy ranges.
In contrast to our hypothesis and to the small reduction in body fat observed in the present study, serum levels of adiponectin did not increase, nor were they different between groups. Although adiponectin is secreted by adipose tissue, secretion of adiponectin is actually inhibited by elevated body fat levels largely because of obesity related inflammation (5,22). Adiponectin has been shown to increase after weight loss (16,20). The BCS in the present study maintained their weight and were well within the normal ranges of adiponectin (0.865–21.4 mg·L−1). The lack of change in adiponectin is in agreement with previous RT (9) and aerobic training (13,27) interventions in healthy postmenopausal women. CRP also did not change during the intervention and, therefore, may have attenuated any changes in adiponectin.
The small changes in FM may have also limited our ability to see changes in CRP. It is also likely that our RT did not change CRP because values were already near optimal (26).
Limitations to the present study include not having a nonexercising control group. However, previous studies that do include a control group have reported significant differences between the exercising intervention groups and the nonexercising control groups in similar variables measured in the present study. Therefore, we believe the findings of the current study make a valuable contribution to the literature investigating the efficacy of RT to improve strength and body composition in BCS. Second, post hoc analysis using the ES of the group–time interaction for our main outcome variable, LM (ES = 0.055), with an α of 0.05 and acceptable power level of 0.8, revealed that a total sample size of 174 BCS (87 per group) would have been required to detect significant interactions for several of our variables. Given the novel nature of the study and the intensity level of the RT intervention, recruiting 174 BCS to participate in a 12-wk exercise intervention would present some challenges. Lastly, our participants changed their dietary intake of food across the 12 wk. Future studies need to carefully educate participants about their food intake and perhaps use dietary food logs more frequently and then analyze the logs immediately to give participants feedback on whether they are adhering to dietary recommendations. More objective methods such as asking participants to take photographs of their meals and mobile phone applications that allow participants to scan the bar codes on the foods they consume may provide a more accurate representation of dietary habits. Because protein is more satiating than carbohydrates and fats (37), perhaps counseling participants on macronutrient types and choices may provide more accurate reporting of dietary habits. Because this is one of the first studies to investigate the use of a protein supplement in combination with RT in BCS, we believe this study can provide a basis for prescribing greater amounts of protein in future studies to improve body composition in both aging adults and the cancer populations. The 40 g·d−1 of protein given in the present study did not increase the levels of IGF-1 to a greater extent than the RT, but this could have been due to the drop in dietary protein. However, neither group had IGF-1 levels increase above normal ranges. The extra protein also did not cause any weight or FM gain.
This is one of only a few studies to demonstrate a significant training effect from RT (2 d·wk−1) on LM gains in female BCS. The observed improvements in LM translated to significant improvements in muscular strength in postmenopausal BCS. Although protein supplementation did not have an added benefit, consumption of 40 g·d−1 in the form of a whey and casein blend protein beverage was well tolerated and adhered to and did not cause weight gain nor did it increase IGF-1 levels above normal. The only exception was a slightly higher upper body training volume (P = 0.07) in the RT + protein group. However, the participants in the RT + protein group reduced their total calories and dietary intake of protein from whole foods, therefore making the difference in the protein intake from baseline to 12 wk 17 g·d−1 and not the 40 g·d−1, which may have influenced the results.
Regardless, a moderate to vigorous training intensity (65%–81%) and volume of RT were safe and provided a sufficient training stimulus to elicit significant improvements in muscular strength and body composition. The efficacy of RT to increase levels of adiponectin and decrease CRP in BCS is yet to be determined.
The authors thank Dymatize® Nutrition for providing the protein supplement and the National Strength and Conditioning Association and Florida State University College of Human Sciences for funding the project. The authors also sincerely thank the breast cancer survivors for their participation in the study. T. A. M., L. B. P., and M. J. O. conceived and designed the study and secured funding for the project. T. A. M. conducted all participant recruitment and data collection and assisted with manuscript preparation. E. A. S. assisted with data collection. L. B. P. helped with the study design and provided oversight of data collection, analysis, and manuscript preparation. M. J. O. and R. J. M. helped with the study design and manuscript preparation. All authors read and approved the final manuscript. The results of the present study do not constitute endorsement by the American College of Sports Medicine.
M. J. O. serves on the scientific advisory board for Dymatize® Nutrition. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.
1. Ahmed RL, Thomas W, Yee D, Schmitz KH. Randomized controlled trial of weight training and lymphedema in breast cancer survivors. J Clin Oncol
2. Arciero PJ, Gentile CL, Pressman R, et al. Moderate protein intake improves total and regional body composition and insulin sensitivity in overweight adults. Metabolism
3. Bayes-Genis A, Conover CA, Schwartz RS. The insulin-like growth factor axis: a review of atherosclerosis and restenosis. Circ Res
4. Bosse JD, Dixon BM. Dietary protein in weight management: a review proposing protein spread and change theories. Nutr Metab (Lond)
5. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab
6. Candow DG, Chilibeck PD, Abeysekara S, Zello GA. Short-term heavy resistance training eliminates age-related deficits in muscle mass and strength in healthy older males. J Strength Cond Res
7. Churchward-Venne TA, Breen L, Phillips SM. Alterations in human muscle protein metabolism with aging: protein and exercise as countermeasures to offset sarcopenia. Biofactors
8. Churchward-Venne TA, Holwerda AM, Phillips SM, van Loon LJ. What is the optimal amount of protein to support post-exercise skeletal muscle reconditioning in the older adult? Sports Med
9. Figueroa A, Vicil F, Sanchez-Gonzalez MA, et al. Effects of diet and/or low-intensity resistance exercise training on arterial stiffness, adiposity, and lean mass in obese postmenopausal women. Am J Hypertens
10. Freedman RJ, Aziz N, Albanes D, et al. Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer. J Clin Endocrinol Metab
11. Friedrich N, Krebs A, Nauck M, Wallaschofski H. Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the Immulite 2500: results of the Study of Health in Pomerania (SHIP). Clin Chem Lab Med
12. Frontera WR, Meredith CN, O'Reilly KP, Knuttgen HG, Evans WJ. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol
13. Giannopoulou I, Fernhall B, Carhart R, et al. Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes. Metabolism
14. Guillet C, Prod'homme M, Balage M, et al. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J
15. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab
16. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol
17. Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr
18. Khan S, Shukla S, Sinha S, Meeran SM. Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets. Cytokine Growth Factor Rev
19. Ligibel JA, Campbell N, Partridge A, et al. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol
20. Matsuzawa Y. Adiponectin: identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler Suppl
21. McIntire KL, Hoffman AR. The endocrine system and sarcopenia: potential therapeutic benefits. Curr Aging Sci
22. Nicklas BJ, You T, Pahor M. Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. CMAJ
23. Ormsbee MJ, Choi MD, Medlin JK, et al. Regulation of fat metabolism during resistance exercise in sedentary lean and obese men. J Appl Physiol (1985)
24. Prado CM, Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr Opin Clin Nutr Metab Care
25. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol
26. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med
27. Ryan AS, Nicklas BJ, Berman DM, Elahi D. Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women. Int J Obes Relat Metab Disord
28. Sakuma K, Yamaguchi A. Sarcopenia and age-related endocrine function. Int J Endocrinol
29. Schmitz KH, Ahmed RL, Hannan PJ, Yee D. Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol Biomarkers Prev
30. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin
31. Simonavice E, Kim JS, Panton L. Effects of resistance exercise in women with or at risk for breast cancer-related lymphedema. Support Care Cancer
32. Simonavice E, Liu PY, Ilich JZ, Kim JS, Arjmandi B, Panton LB. The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors. Appl Physiol Nutr Metab
33. Sweeney C, Schmitz KH, Lazovich D, Virnig BA, Wallace RB, Folsom AR. Functional limitations in elderly female cancer survivors. J Natl Cancer Inst
34. Tieland M, Dirks ML, van der Zwaluw N, et al. Protein supplementation increases muscle mass gain during prolonged resistance-type exercise training in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc
35. Tudor-Locke C, Bassett DR Jr. How many steps/day are enough? Preliminary pedometer indices for public health. Sports Med
36. Villaseñor A, Ballard-Barbash R, Baumgartner K, et al. Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL study. J Cancer Surviv
37. Westerterp-Plantenga MS, Nieuwenhuizen A, Tomé D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr
38. Winters-Stone KM, Dobek J, Bennett JA, Nail LM, Leo MC, Schwartz A. The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv
39. Winters-Stone KM, Dobek J, Nail L, et al. Strength training stops bone loss and builds muscle in postmenopausal breast cancer survivors: a randomized, controlled trial. Breast Cancer Res Treat