The purpose of a scoping review is to map existing literature on a certain topic that may be of complex or heterogeneous nature and describe the volume, nature, and characteristics of the primary research.1 Thus, a scoping review aims to present an overview of a potentially large and diverse body of literature. This scoping review focuses on weight changes during and after antineoplastic treatment for breast cancer (BC). This are of concern because of the association between fat tissue, BC development, and the increased risk of both recurrence and early death found among breast cancer stricken women with relative weight variations of 5%.2
Weight changes in women with BC have been investigated for decades.2–10 Studies have found that women in current adjuvant chemotherapy (CT) for BC on average gain 2.0 kg during and after adjuvant treatment, and weight gain up to 10.0 kg is not uncommon.5 A main contributor to weight gain is suggested to be the duration of CT.6–8,10,11 However, with current antineoplastic agents, for example, anthracycline-based CT (anthracy-CT), weight changes may be overestimated.12 Nevertheless, Makari-Judson et al13 found weight gain ranging from 1.6 kg at 1 year to 6.0 kg at 2 years. Adjuvant cancer treatment involves radiotherapy, as well as CT, and endocrine treatment (ET).14 Some researchers point at ET and menopause status as a contributing factor. For example, Goodwin et al4 and Ganz11 found onset of menopause and CT contributed to weight gain. Yet, findings are inconclusive as some studies suggest premenopausal status to be a predictor,3,8,9 whereas others claim that menopausal status does not influence weight gain.5,15,16 Recently, a review identified the effect of ET on weight gain including studies that compared estrogen receptor antagonist (ERA), aromatase inhibitors (AIs), and placebo.17 Although there was no significant difference between the groups, the authors pointed at inconsistent results and the need for further investigations.
Despite investigations for years, findings on weight changes during and after adjuvant treatment for BC are diverse. Thus, the aims of this scoping review was to investigate changes in weight associated with contemporary anticancer medication and examine factors that might influence the assessment and diversity of the findings.
Materials and Methods
This scoping review was conducted by a research team consisting of health professionals with clinical and research experience. With inspiration from the original framework by Arksey and O'Malley,1 the review consisted of 5 steps: identify the research question; find relevant studies; select the studies relevant for the study; chart the data; and collate, summarize, and report the results.
The Research Question
Our research question was: What is known from the existing literature about the extent and patterns of changes in weight among women during and after current adjuvant standard antineoplastic treatment for BC?
Find and Select Relevant Studies
The literature search was conducted in collaboration with a librarian from a university hospital. Although scoping reviews tend to comprehensively search all unpublished and published studies, we selected only published studies sought by means of databases. The literature search was conducted in PubMed, CINAHL, and EMBASE using MeSH terms, CINAHL terms, and Emtree, as well as free text not to exclude relevant literature in the databases search (Table 1). The search in PubMed provided most articles, and the search string from PubMed is shown in Table 2. The titles were initially screened and included for further investigation if they seemed to be relevant to the topic. Review articles and articles without abstract were excluded. During further screenings of abstracts and full-text readings, primary research focusing on women with BC receiving antineoplastic treatment with anthracy-CT and/or endocrine therapy and weight changes was included.
Weight changes have been described in different terms. Thus, we included studies that reported relative weight changes (percent), absolute changes (in kilograms) and body mass index, and body composition terms (fat mass, fat-free mass, and total body water). A flowchart illustrates the selection process of the included studies investigating the associations between weight changes and treatment with anthracy-CT ± ET or ET as a standalone treatment (Figure).
Chart the Data, Collate, and Summarize
A matrix charting detailing information of data was developed and consulted with the research team. The first author, who was familiar with the data in its entirety, extracted and categorized the data. Study design, aim, sample size, treatment, measure points, technique, and cutoff are charted in Table 3 and briefly reported narratively in the text. Subsequently, the specific findings were collated and summarized narratively using a thematic construction regarding weight changes divided into 4 follow-up periods: short-term, after 1 year, after 18 months/2 years, and after more than 2 years (Table 4). Scoping reviews have recently been methodologically developed to also contain a step for “synthesizing findings.”33,34 As such, the findings are continuously synthesized. The optional consultation exercise described by Arksey and O'Malley1 was not conducted. However, 2 members of the research team, who are considered clinical experts, verified the relevance of the findings. In accordance with the purpose of scoping reviews, we did not appraise the quality of data extracted before inclusion.
The review reports findings from 19 studies published from 2004 to 2017 (Table 3). Assessing studies published from 2004 and onward, 2 studies report changes in weight associated with ET as the main focus.20,30 Four studies report findings on CT,19,23–25 and 13 studies, reporting findings on CT, included the effect of ET.6,7,10,12,18,21,22,26–29,31,32
Characteristics of Study Design and Data Collection
The studies were conducted almost worldwide displaying findings from Europe (5), North and South America (6 and 2), and Asia (6).
The majority of the studies had a retrospective design6,10,23–32 and examined BC stages I to III.6,10,23,24,28 Most of the studies included between 100 and 350 participants, and 2 included more than 3000 women.6,27 In several studies, the methods used to estimate weight changes were not described10,24,26,29,31,32 or did not specify the exact CT regimens.27,32 If the regimens were specified, the women received various regimens,6,10,23–26,28,29,31 and the descriptions of ET differed. In most studies, ET followed CT. However, in addition to the retrospective study focusing on ET,30 ET was also given as a standalone treatment and reported separately in 3 studies.6,10,31 Cutoff points for assessing weight changes were either missing23,28,30 or defined as absolute weight changes ranging from 1.0 to 2.5 kg,24,27,30–32 relative weight changes of ±5%,6,25,29,31 or as the difference between measurements.10,31
Of 7 studies with a prospective design,7,12,18–22 5 included women with BC in stages I to III,18–22 and 2 included women in stages I to II.7,12 The samples consisted of 20 to 272 women, and follow-up time varied from completed CT (approximately 4–6 months) and up to 2 years. Most studies ended measurement after 1 year.7,18–20 Chemotherapy regimens were specified in 6 studies,7,12,18–22 and one study reported findings from ET alone.20 If cutoff points for assessing weight changes were described, they were defined as absolute weight changes of ±2.5 kg12 and relative changes of ±2.4%21 or ±5%.19 One study applying a retrospective and prospective design included approximately 6000 women, but attrition was 2000 women at the 3-year follow-up.32
Reviewing and Synthesizing Findings in a Time Perspective
Reviewing the articles and synthesizing findings from baseline until 10 months after baseline showed that 13 of the studies reported weight changes short term.10,12,18–25,28,29,32 The changes in weight and body composition were mainly related to CT except in the study of Francini et al.20 In addition, ET was reported as a standalone treatment in the studies of Pedersen et al21 and Basaran et al.10 In the last case, there were only 5 persons in this group; thus, these findings are omitted from this review.
Francini et al20 evaluated the changes in body composition among postmenopausal women that changed treatment from ERA to AI. They found decreasing weight and fat mass in the AI group and decreasing weight and stable fat mass in the ERA group. The differences were not statistically significant from baseline. However, the changes reported by Pedersen et al21 among mainly postmenopausal receiving AI displayed no changes in weight or fat mass. Thus, studies reporting short-term follow-up on ET seem not to provide a common direction.
Changes related to CT showed a mean or median weight gain ranging from 1.0 kg to 4.2 kg12,19,21,22,25,29,32 or a relative weight gain ranging from 2.2% to 7.4%.10,22,32 Although all included studies applied anthracy-CT, the CT regimens could vary in lengths and numbers of drugs, and some reported findings in a mixed group including non–anthracy-CT.
The unclear findings associated with short-term ET are also manifest with respect to changes in weight and body composition after CT. For example, Han et al28 reported stable weight but without body composition data. These details were shown in Freedman and colleagues'18 study, which found a minimally increased weight of 0.27 ± 4.6 kg (P = .85) at 10 months, but a statistically significant (P = .03) decrease in fat-free mass. Fluctuation in body composition may thus appear despite stable weight. On the contrary, Ingram and Brown12 and Pedersen et al21 found a larger mean weight gain (1.4 and 1.6 kg, respectively) with an increase in fat-free mass among women given AC (adriamycin, cyclophosphamide)12 or AC-T (adriamycin, cyclophosphamide, taxanes) (P < .0001)21 apparently caused by water retention. In the last case, the women were mainly premenopausal. On the other hand, increasing fat mass was found in a mixed group given CEF (cyclophosphamide, epirubicin, fluorouracil) or CMF (cyclophosphamide, methotrexate, fluorouracil),12 which was suggested to be caused by the longer duration of treatment with CEF and CMF.12
AC treatment has a shorter duration than CEF, CMF, or AC-T, and the duration of CT as a main factor for weight gain is supported by the study of Ricci et al.23 They found that specifically AC-T regimens had the highest risk of weight gain 1 month after completing CT compared with other regimens. The body mass index changes from 27.4 kg/m2 to 28.3 kg/m2 (P < .001). The women in the AC-T group were younger (54.2 ± 11 years) than women in the other regimens (59.3 ± 11.2 years) (P = .007).23 In this case, it is unknown whether the changes consist of increased body water.
As opposed to Ricci et al,23 Vargas-Meza et al25 found no differences in weight whether the regimens were anthracycline based or not. In their study of 200 women, 155 women gained weight, of whom 41 gained between 6% and 10%, and 19 gained more than 10%.25 Thus, 60 women had serious weight gain of concern for survival and recurrence. Although the weight did not differ between premenopausal and postmenopausal women, a higher percent of premenopausal women gained weight. Finally, Wang et al24 found an even distribution in stable weight, weight gain, and weight loss. They point at young age at diagnosis (P = .028) and the duration of CT (P = .037) as contributing factors for weight gain, whereas there was no correlation between menopause and weight.
Synthesizing these short-term findings, weight gain after CT is common and may exceed 5% relative weight gain of concern for recurrence and survival. As few studies report body composition changes, it is difficult to provide a common picture of the pattern of the changes in the short term. However, weight gain may be associated with increased fat-free mass due to water retention or increased fat mass due to longer duration of CT. Treatment with ET alone seems to point in different directions showing decreasing weight and fat mass in postmenopausal women given AI or no changes among primarily postmenopausal women given AI.
Nine studies reported findings at 1-year follow-up.7,10,19–21,26,28,29,31 The pattern of the changes was centered on weight gain as the main result during and after CT.7,10,19,21,26,31 The mean weight gain ranged from 0.9 to 3.9 kg,19,21,31 and relative weight gain ranged from 0.39% to 5.9%.10,19,26 In some studies, the amount of women gaining weight increased compared with short-term measurement. Basaran et al10 reported an increase from 67% to 72%. Similarly, Tredan et al19 showed a difference from 52.1% to 59.7% in a cohort of 272 women, of whom 233 were given anthracy-CT. Forty percent of those who gained weight increased their weight by more than 5% in the short term, increasing to 45% at 1 year. Although Chaudhary et al26 report a minimal mean weight gain of 0.39%, they found a statistically significant difference when they investigated associations between menopause status and tumor stages.
Body composition changes showed a tendency toward increasing fat mass and decreasing fat-free mass.7,21 Gordon et al7 found increased fat mass, especially in the trunk in their study of 43 premenopausal women in different treatment regimens. The data were unified and calculated for the whole group. Thus, the analysis does not account for changes in women given anthracy-CT, who provided only one-third of the data.
Heideman et al31 calculated weight changes in groups receiving no treatment, CT alone, CT ± ET, or ET alone. They found weight gain in all groups with the highest gain when receiving CT ± ET. This is contradictory to the findings of Jeon et al29 and Han et al,28 who reported stable weight at 12 months. In addition, Han et al28 found weight loss of 1.17 kg among women who did not receive ET. These findings suggest that treatment with ET impacts weight development but ambiguously. For example, weight increased among women given ET alone,31 whereas changes in weight and fat mass associated with ET alone was found stable at 1 year in another study.21 Investigating the difference between ERA and AI, weight among women receiving ERA remained stable, whereas weight and fat mass decreased in the group receiving AI.20
Synthesizing findings at 1 year, weight tended to increase from baseline among women given CT partly as increasing fat mass. The effect of CT still seems essential as CT alone or followed by ET may lead to increasing weight. However, the findings lack unequivocalness as weight was found to be stable or decreased when CT was given alone. Thus, the effect of ET on weight at 1-year follow-up seems ambiguous pointing at weight gain, stable weight, and weight loss.
Eighteen-Month to 2-Year Follow-up
Seven studies reported findings in the time span from 18 to 24 months.21,22,27–30,32 Weight gain as the main result during and after CT ranged from 0.7 to 2.6 kg.21,22,32 According to Pedersen et al,21 the women had an average gain of 1.4 kg consisting of increased fat mass (P = .007). Chen et al27 reported a mean weight gain of 1.7 kg, and with a cutoff of 2 kilos, 61% gained weight, 14% lost weight, and 25% had no weight change. In the weight gain group, 37% gained 5% or greater, and 17% gained more than 10%. These findings were associated with young age and being premenopausal.27 In support of these findings, Gu et al32 demonstrated a median weight gain of 2.0 kg showing that 33% had weight gain of 5% or greater. Gu et al32 and Chen et al27 reported findings from anthracy-CT, whereas Liu et al22 reported relative weight changes divided into anthracy-CT and non–anthracy-CT. They found that anthracy-CT regimens showed a slower and milder increase compared with other chemotherapeutic regimens and the highest changes among women in non–anthracy-CT (mean, 2.6 kg [4.7%]) compared with anthracy-CT (mean, 0.7 kg; 1.2%).
Although Heideman et al31 claimed that a majority of women receiving CT ± ET displayed weight gain, stable weight was present in the studies of Han et al28 and Jeon et al.29 Weight also remained stable at 18 months among the women receiving ET (majority AI) alone in the study of Pedersen et al.21 However, Nyrop et al30 illustrated that weight changes at 24 months after initial CT involve almost an equal division in weight gain, stable weight, and weight loss. Weight gain in the 39% women was especially noted among women given CT and was not associated with the kind of ET given.
Synthesizing the findings in the time span 18 to 24 months from diagnosis, weight gain appeared commonly and in some cases reported to exceed 5% relative weight gain among a majority of women. The difference between anthracy-CT and non–anthracy-CT with or without ET is not clear. More studies reported stable weight or approximately the same amount of weight gain among women in anthracy-CT than in women receiving non–anthracy-CT. No changes appeared when ET was given alone, and a possible weight gain was associated only with CT and not the kind of ET.
Long-term Follow-up—More Than 2 Years
Three studies reported findings in the time span more than 2 years.6,31,32 Examining the association between different CT regimens, ERA use, and weight gain, Saquib et al6 found significant weight gain ≥ 5%. All types of CT were significantly associated with weight gain (odds ratio, 1.65; 95% confidence interval, 1.12–2.43) as opposed to ERA (odds ratio, 1.03; 95% confidence interval, 0.71–1.51).
Heideman et al31 found a mean weight gain of 2.4 kg in the total group. Weight in the no-treatment group appeared stable. A minimal increase in ET-only group (mean, 0.9 kg) was found, and the highest weight gain among women given CT or CT + ET of 2.9 and 4.7 kg, respectively. The last group displayed the largest weight gain at 5 years as 46.9% gained more than 5% mean 4.7kg (SD 6.3; P<.05). No significant changes were found among women receiving ET alone. Although Gu et al32 at this time span found decreasing median weight gain equivalent to 1.0 kg compared with 18 months' measurement, 33% of the women still had weight gain of 5% or greater that was associated with being younger, being premenopausal, and receiving CT.
Synthesizing long-term findings shows how women, initially treated with CT, suffer from persistent serious weight gain in the long term compared with baseline. Endocrine therapy induces none or minimal long-term weight.
REVIEWING AND SYNTHESIZING OTHER CONTRIBUTING FACTORS FOR WEIGHT GAIN THAN TREATMENT
In this review, contributing factors for especially weight gain were reported and discussed. A central topic was menopause status, and especially premenopause seems to be an essential topic for further investigation.23 Although menopause status was suggested not to influence weight,25 this review showed that independent of time span, being premenopausal seems to induce weight gain.10,21,26,27,31,32 In addition, premature menopause needs to be observed as a contributing factor that may influence body composition changes.7 Related to this, age, especially being young, may be a crucial factor.10,21,27,32 Besides this dominant topic, other contributing factors for weight changes such as comorbidity,10,27 daily caloric intake,25 lifestyle,27,28 prediagnostic weight,27,32 and disease stage were found.26,27,30
This scoping review reports findings from 19 articles identified through a systematic literature search. The review demonstrated a diversity of studies regarding changes in weight that might influence the possibility of making synthesis and thus providing useful recommendation for practitioners. In addition, the article has shed light over factors that might influence the assessment and diversity of the findings.
The review shows that several studies have investigated changes in weight, while fewer included body composition measurements.7,12,18,20,21 In general, the studies display different treatment modalities, the sample sizes in the retrospective studies suffer from dropout, and the prospective studies from small samples. In addition, weight may be self-reported and on different scales if mentioned at all. Although the studies selected for review investigated modern/third-generation chemotherapeutic agents, the specific modalities were not described in all cases. Thus, due to differences regarding study designs, sample sizes, treatment regimens, measure points, and techniques, the option for a clear picture of the changes is troublesome. The same limitations appear in a review on weight changes during adjuvant ET (alone) conducted by Nyrop et al.30 Investigating 38 studies, they reported that most studies showed no significant difference whether ET was compared with placebo or AI was compared with ERA. However, because of methodological issues, they were not able to draw a firm conclusion, and they recommend further studies.
Research has focused on weight gain as a contributing factor to recurrence and decreased survival among women treated for BC.5–8,10 Thivat et al2 point at a weight variation of more than 5% from diagnosis to completed CT as having a negative impact on recurrence and survival assessed during a 20-year follow-up. Furthermore, a relative weight loss of 2.4% may have influenced the survival rate among a mixed group of cancer patients, including women with BC.35 In both studies, women with stages I to IV BC participated. Stage IV BC is characterized by distant metastases and a severe prognosis that may have influenced the findings. Although some studies in this present review apply a 5% cutoff,6,19,25,29,32 it may be difficult to evaluate whether the changes in general are more or less than the serious relative changes crucial for recurrence and survival, when most studies apply no cutoff or use factual kilos as cutoff values.7,10,12,18,20–24,26–28,30,31
In assessing the studies across, it seems that anthracy-CT regimens given in combination with other chemotherapeutic agents are essential for weight gain due to the duration of the treatment.12,21,23 Whether the women received ET as follow-up treatment seems not to influence these findings.6,30 The duration of CT as a main factor and the lack of influence from ET correspond with the findings of Vance et al.8 In this review, they included studies from 1997 up to 2009 and did not describe the specific CT regimens. Thus, an unknown amount of studies may report findings from former regimens and not anthracy-CT. However, the risk of weight gain needs attention as recently the Danish Breast Cancer Group14 recommended additional series of taxanes in BC treatment, which may increase the risk of weight gain in the future due to prolonged duration.
In addition, it appears that most studies agree about the risk for weight gain among younger premenopausal women.7,21,23–27 Although the average weight gain and the association with being young and premenopausal are supported in other studies,8 the samples consist of women in different stages: I to II,7 I to III, and21,23,24 0 to IV,26,27 which may influence the findings.
Weight changes after completing CT up to 1 year seem critical,6,10,12,19,21,22,28,29,31 as more studies reported statistically significant weight gain at this measure point.21,26,29 Still, after completed CT, weight gain may consist of water retention that disappears over time.12,21 Nevertheless, some studies demonstrate no changes at 1 year,28,29 while others claim persistent weight gain.10,19,31 In some studies, the weight continues to rise or does not return to baseline weight,6,21,22,31 whereas others conclude no changes at the 2-year follow-up.28,29 Sheean et al36 also described this diversity of findings. In contrast to the 2 studies in the present scoping review showing increased weight and decreased fat mass due to increased body water short term, they point at stable or increased fat mass after completed CT. The tendency of increasing fat mass appeared also at later measure points such as 1-, 2-, and 3-y follow-up. However, in this review, there was no description of the specific CT regimens.
Only studies from database searching in English or Nordic language were included in this review. Although these limits may have excluded potential relevant literature, we anticipated that this specific topic regarding changes in weight during and after current standard adjuvant antineoplastic treatment for BC would be covered in scientific databases. We were inspired by Arksey and O'Malley's1 original framework for scoping reviews and followed their recommendations and additionally included synthesizing, as there is an increasing attention on synthesizing and using scoping review for clinical recommendations.33,34 Despite this, our scoping review must be used with caution due of the diversity in study designs and findings.
This scoping review illustrates how findings in weight and body composition changes fluctuate over time and vary dependent on measure points. In addition, the studies apply different cutoffs, which make it difficult to evaluate the changes in relation to the serious relative changes crucial for recurrence and survival. The diversity impacts the synthetization of findings and the possibility to provide clinicians with evidence-based knowledge to use when providing information to women with BC.
Despite these difficulties, synthesizing findings over time illustrates the need for attention on younger premenopausal women given CT. To gain more knowledge about the exact changes in weight and body composition, monitoring these variables for at least 2 years may be essential as short-term changes may be caused by increased body water, whilst long-term changes seem to be related with increased fat mass.
Based on this review, we recommend further investigations applying long-term prospective designs, measurements at certain time points, and assessing weight and body composition changes via the same kind of device. For example, bioelectrical impedance analysis that is cheap and easy to use could help to standardize measurement. In addition, to show the patterns of weight loss, stable weight, and weight gain requires inclusion of women given the same antineoplastic treatment in relevant numbers for statistical analysis and using the same cutoff, for example, 5%.
Given the association between weight gain and risk for recurrence and increased mortality,2,37 developing evidence-based knowledge on weight changes during antineoplastic treatment for BC is important. Moreover, weight changes may influence the women's perception of their bodies38 and quality of life, although mean weight gain may be assessed as modest.39 Thus, future research may focus on changes in body weight including body composition among women treated for BC as well as the women's experiences of the changes.
The authors acknowledge the Clinic for Surgery and Oncology, Aalborg University Hospital, and Clinical Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark, for supporting this work.
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