Cancer is a critical global health concern since it is the world's most common non-communicable disease and the second major cause of death (Afolabi et al., 2022b; Meneses-Echávez et al., 2015). More specifically, breast cancer (BC) is the most frequent type of cancer in women, and 25% of BC cases are due to excessive weight and sedentary lifestyle risk factors (Siegel et al., 2020). Thus, obesity affects one out of every three BC survivors (Greenlee et al., 2016), raising the chance of cancer recurrence, comorbidity, and mortality (Feliciano et al., 2019; Hwangbo et al., 2018; Lohmann et al., 2021; Petrelli et al., 2021). Given that fat tissue is an endocrine organ that secretes various inflammatory factors and adipokines (Afolabi et al., 2022a), a significant association between BC and numerous impaired cardiometabolic health-related indices has been documented in women (Chowdhury et al., 2021; Guo et al., 2013; Wu et al., 2009). BC survivors are at a high risk of developing comorbidities, such as hyperlipidemia, sarcopenia, and osteoporosis (Ording et al., 2013), which affect individuals' quality of life (QoL), cardiorespiratory fitness, physical function, and bone health while increasing cancer-related pain and fatigue (Al-Mhanna et al., 2022; Ganz, 2006; Stanton, 2006). Also, excess adiposity is linked to early recurrence on breast cancer survivors after treatment, showing that the management of obesity may be a critical health factor for this cohort (Acevedo et al., 2022; Elreda et al., 2022).

Regular exercise has been reported as a vital tool for reducing the most common and impairing symptoms in BC patients before, during, and after treatment (Mortimer et al., 2010; Mutalub et al., 2022). In BC patients and survivors, exercise is considered an effective non-pharmacologic method for lowering pro-inflammatory biomarkers and cardiovascular disease (CVD) risk factors as well as mental health, and physical function (Campbell et al., 2019; Speck et al., 2010; Van Alsten et al., 2020). However, exercise oncology has not been yet established as an emerging trend among practitioners in the health and fitness community (Newsome et al., 2024). In terms of the mechanism behind the positive role of exercise in BC, exercise-induced reductions in hyperlipidemia and chronic inflammation are believed to inhibit tumor growth by lowering serum cholesterol levels and reducing the exposure of tumor cells to cholesterol, increasing anti-tumor immunity, and regulating tumor vasculature (Betof et al., 2013). In addition, exercise can reduce blood lipid levels by improving skeletal muscle's ability to use lipids instead of glycogen or increasing lecithin-cholesterol acyltransferase and lipoprotein lipase activity (Al-Mhanna et al., 2024a; Al-Mhanna et al., 2024b; Mann et al., 2014). Also, exercise may counteract the pro-tumor impact of hyperlipidemia by reducing chronic inflammation, lowering serum lipids, improving the immune system's ability to identify and destroy tumor cells, and stabilizing the tumor's vascular network (Gonzalo-Encabo et al., 2022).

Although many trials show that exercise may improve body composition in BC patients (Almstedt et al., 2016; Dieli-Conwright and Orozco 2015), there is a lack of evidence synthesis and pooled outcomes via meta-analysis that evaluated the effectiveness of combined aerobic and resistance training (CART) among BC patients with overweight/obesity (Dieli-Conwright et al., 2022; Jones and Courneya, 2002; Milne et al., 2008a). Furthermore, the long-term implications of CART in women with BC remain unclear (de Paulo et al., 2018), indicating that more research is required, aiming to investigate the effects of CART on body composition and several cardiometabolic health aspects as previously reported (de Paulo et al., 2018).. Thus, the present review aimed to assess the effects of CART on anthropometrics, body composition, lipid metabolism, inflammation, adipokines, QoL, sleep quality, and fatigue among women with BC and overweight/obesity.

This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines (Page et al., 2021). The study protocol was registered in the International Prospective Register of Systematic Reviews (ID: CRD42022308214).

Articles were retrieved from PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar after a systematic electronic search. Four authors (S.A., B.K., A.B., and H.A.) employed a combination of keywords and Boolean operators, specifically "OR" and "AND" in conducting an electronic search of literature up to January 8, 2024. The keywords utilized were ("Breast Cancer" OR "Breast Neoplasm") AND "(Overweight" OR "Obese") AND "(Exercise" OR "Training") to retrieve pertinent material (Table S1). The PICOS was used to formulate the research questions for systematic reviews and meta-analyses as follows: (P) Population: BC patients with overweight or obesity; (I) Intervention: CART; (C) Comparator: standard treatment (ST) (patients who did not perform any exercise); (O) Outcomes: [primary: body weight (BW), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), body fat (BF), fat mass (FM), fat-free mass (FFM); secondary: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), C–reactive protein (CRP), Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-6 (IL-8), natural killer (NK) cells, adiponectin (ADPN), leptin (LEP), cancer-related fatigue (FA), sleep quality (SQ), and QoL]; and (S) Study type: randomized controlled trials (RCTs). The reference lists of included articles were searched for articles that met the inclusion criteria as well as the reference lists of all relevant systematic reviews.

Studies were considered eligible for inclusion if the following criteria were met: (i) participants were BC patients with overweight (BMI 25-29.9 kg/m²) or obesity (BMI ≥30 kg/m²); (ii) no specified age limit for participants; (iii) the intervention used in the studies was CART; (iv) articles provided full-text accessibility and were published in a refereed journal from inception up to 8 January 2024; (v) no language restrictions; and (vi) studies were RCTs. The following were excluded: (i) studies involving a mixed sample of individuals (e.g., underweight or normoweight BC patients or overweight/obese people without BC); (ii) articles where the effects of CART cannot be isolated because exercise training was involved as part of a multicomponent intervention (e.g., diet and exercise intervention); (iii) studies where the control group performed exercise; (iv) articles that did not assess the outcome measures of interest; (v) studies that used an acute exercise intervention (e.g., single bout or duration ≤2 weeks); and (vi) review articles, case reports, studies lacking a control group, and ambiguous or unclear data.

The screening process was conducted collaboratively among four authors (S.B.A.L., B.K., A.B., and H.A.), who independently evaluated publications based on titles, abstracts, and full texts (in instances of uncertainty). In cases of conflicts or uncertainties, a fifth author (A.A.I.) was involved in the resolution. While the screening was not conducted in duplicate, it involved thorough evaluation by Multiple authors to ensure robust inclusion and exclusion criteria were applied consistently. Additionally, literature management software (EndNote X9, Clarivate Analytics, Philadelphia, PA, USA) was utilized to manage the records of the literature search.

Two authors (S.B.A.L. and A.A.I.) independently sampled and extracted data from the relevant studies after reading the full text. The included investigations generated a significant amount of data that was retrieved and published, consisting of the first author, population, publication year, gender, sample size, and exercise intervention details (frequency, intensity, time, and type), study duration, and outcome measures.

Two authors (S.B.A.L. and A.B.) independently assessed the risk of bias from individual studies according to the Cochrane Handbook for Systematic Reviews of Interventions [35]. The overall risk of bias assessment for each eligible study was judged considering the following factors: (i) random sequence generation; (ii) allocation concealment; (iii) blinding of participants and personnel; (iv) blinding of outcome assessors; (v) completeness of outcome data; (vi) selectivity of outcome reporting; and (vii) other biases as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Table S2). Eligible studies were classified into three levels of risk of bias (e.g., high, some concerns, and low) by the number of factors for which high, unclear, or low risk of bias potentially existed.

We performed the meta-analyses using Review Manager 5.4 software (Cochrane Collaboration, https://revman.cochrane.org/info) and reported the results of the random-effects model. Thresholds for the interpretation of the I² statistic can be misleading since the importance of inconsistency depends on several factors. We used the guide to the interpretation of heterogeneity as outlined: 0–40% might not be important; 30-60% may represent moderate heterogeneity; 50-90% may represent substantial heterogeneity; and 75-100% would be considerable heterogeneity (Higgins and Green, 2008). Mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CI) were applied to calculate the effect size. MD was used when the outcome measures were comparable across studies and were measured on the same scale, while SMD was used when the outcome measures were measured on different scales or were using different units across studies. The preference between MD and SMD was dependent on the nature of the outcome measure and the heterogeneity of the included studies.

The choice between fixed effects and random effects models depends on the assumption about the homogeneity of the study populations and protocols. The fixed effects model assumes one study population and protocol, generalizable to them; while the random effects model assumes various populations and protocols, generalizable to the entire universe of studies. In this study, we did not use the fixed effects model because it includes studies from various populations, making the results generalizable to the entire universe of studies. A two-sided p < 0.05 was considered to indicate statistical significance.

Two authors (S.B.A.L. and A.B.) independently assessed the quality of evidence for primary and secondary outcomes according to GRADE methodology (GRADEpro, 2014) for risk of bias, inconsistency, indirectness, imprecision, and publication bias; classified as very low, low, moderate, or high. In cases of conflicts or uncertainties, a third author (N.H.A.) was involved in the resolution. Evidence may be upgraded based on factors such as large effect size, dose-response gradient, or when all plausible confounding would reduce a demonstrated effect or suggest a spurious effect when results show no effect. Downgrading factors may include risk of bias, inconsistency of results, indirectness of evidence, imprecision, and publication bias (Table 2).

We conducted a subgroup analysis when the I² statistic was more than 50%. Subgroup analysis was done on the duration of the intervention on the studies investigated the effect of CART on BMI, whether the studies were conducted for ≤16 weeks or >16 weeks.

We performed a sensitivity analysis to investigate the impact of the risk of bias for performance bias and detection bias.

From the specified databases, PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar (Figure 1), a total of 21,751 studies were obtained. After removing duplicate articles, the number of studies eligible for further evaluation was reduced to 20,684. Through a review of the titles and abstracts based on predetermined inclusion and exclusion criteria, 20,643 studies were excluded. Subsequently, the full text of the remaining 41 articles was carefully examined, excluding 18 articles with reasons (Table S3). Therefore, 23 records were included in this study. However, six records were subsequent studies of eligible trials included in this review (Table S4). Hence, 17 studies (RCTs) were finally included in this review, and data were extracted from 1,148 patients who met the eligibility criteria.

Sixteen out of the 17 RCTs were from high-income countries (Battaglini et al., 2007; Brown et al., 2021; Dieli-Conwright et al., 2018; Dieli-Conwright et al., 2022; Dieli-Conwright et al., 2019; Hutnick et al., 2005; Jones et al., 2020; Lee et al., 2019; Ligibel et al., 2008; Ligibel et al., 2019; Mutrie et al., 2007; Nieman et al., 1995; Rogers et al., 2013; Rogers et al., 2014; Saxton et al., 2014; Scott et al., 2013), and one trial from upper-middle income country (Ergun et al., 2013). Thirteen out of the 17 trials recruited their respondents from hospital settings (Battaglini et al., 2007; Dieli-Conwright et al., 2018; Dieli-Conwright et al., 2022; Dieli-Conwright et al., 2019; Ergun et al., 2013; Lee et al., 2019; Ligibel et al., 2008; Ligibel et al., 2019; Mutrie et al., 2007; Rogers et al., 2013; Rogers et al., 2014; Saxton et al., 2014; Scott et al., 2013). Participants in one trial were recruited using a variety of active and passive outreach methods (Brown et al., 2021). In two trials, participants were recruited through advertisements placed in local newspapers (Hutnick et al., 2005; Jones et al., 2020). Meanwhile, in one trial, information regarding the recruitment of participants was not provided (Nieman et al., 1995). Eight out of the 17 trials performed the exercise intervention at health care sites (Battaglini et al., 2007; Dieli-Conwright et al., 2018; Dieli-Conwright et al., 2019; Ergun et al., 2013; Jones et al., 2020; Lee et al., 2019; Saxton et al., 2014; Scott et al., 2013), while nine trials conducted the exercise intervention at both a healthcare site and participants' home (Brown et al., 2021; Dieli-Conwright et al., 2022; Hutnick et al., 2005; Ligibel et al., 2008; Ligibel et al., 2019; Mutrie et al., 2007; Nieman et al., 1995; Rogers et al., 2013; Rogers et al., 2014). The length of the exercise intervention ranged from 8 to 52 weeks (8–12 weeks: 35%; 16–52 weeks: 65%). Table 1 shows the characteristics of the included trials.

The summary of the risk of bias assessment is shown in Figure 2. Details of the risk of bias judgment per domain for each study are provided in Figure S1. In the majority of the trials across most domains, the risk of bias was low or unclear. There was no indication of selective reporting bias. The lack of sufficient random sequence generation in the original study might cause treatment effect bias in both the original studies and the following review findings. The risk of performance bias was presented in seven trials, which was unclear in three trials owing to a lack of details concerning the blinding of the participants, while in four trials the participants were not blinded and hence considered as a high-performance bias. Table S2 details the risk of bias assessment.

The certainty of findings for the outcomes ranged from very low to low, with the downgrading of evidence primarily due to several factors. These included small sample sizes in both control and intervention groups across the included studies, a high risk of bias, as well as moderate, considerable, and substantial heterogeneities. Table 2 details the summary of quality assessment findings.

BW and BMI were reported in five and six trials involving 455 and 429 participants, respectively. No difference was found in BW between CART and ST (Figure S2 and Table 2), while CART reduced BMI (SMD -0.57 kg/m², 95% CI -1.12 to -0.02; I² = 84%; p = 0.04) compared to ST, showing very low certainty. A subgroup analysis showed that short- [≤16 weeks; (four studies, n = 368); SMD -0.21 kg/m², 95% CI -0.42 to -0.00; I² = 0%; p = 0.04], but not long-term [>16 weeks; (two studies, n = 61)] interventions exhibited more favorable effects on BMI than ST (Figure S3 and Table 2). Subgroup analysis is done for BMI. The substantial heterogeneity could not be explained by subgroup analysis according to the duration of the intervention. WC and HC were reported in two trials involving 191 patients. CART induced a significant improvement in HC (Figure S4 and Table 2), demonstrating low certainty (MD -3.14 cm, 95% CI -4.77 to -1.52; I² = 0%; p = 0.02), but not in WC (Figure S5). WHR was reported in (two studies, n = 122) with no meaningful changes between CART and ST (Figure S6). There were no significant changes in the effect estimate after the sensitivity analysis for Mutrie et al. (2007) was done on the BW, BMI, FA, and QoL parameters. There were no significant changes in the effect estimate after the sensitivity analysis for Hutnick et al. (2005) was done on BW, BMI, BF, and IL-6. However, Sensitivity analysis for WHR outcome in Ligibel et al. (2008) shows changes in the effect estimate (MD - 1.10, 95% CI -0.16 to -0.04, I² statistics = 0%, p = 0.02).

BF, FM, and FFM were assessed in (six studies, n=305), (four studies, n = 347), and (two studies, n = 111) trials, respectively. CART induced favorable reductions in BF (SMD -0.50%, 95% CI -0.93 to -0.07; I² = 68%; p = 0.02; very low certainty) (Figure S7 and Table 2) and FM (SMD -0.63 kg, 95% CI -1.23 to -0.04; I²=83%; p = 0.04; low certainty) compared to ST (Figure S8 and Table 2). In FFM, ST showed a greater increase (SMD 1.03 kg, 95% CI 0.63 to 1.43; I² = 0%; p < 0.001; low certainty) than CART (Figure S9 and Table 2). There were no significant changes in the effect estimate after the sensitivity analysis for Battaglini et al. (2007) was done on FFM.

TC, HDL-C, LDL-C, and TG were evaluated in (two studies, n = 170), (three studies, n = 261), (two studies, n = 111), and (one study, n = 91) trials, respectively. CART exhibited significant improvements in TC (SMD -0.95 mmol/L, 95% CI -1.37 to -0.52; I² = 43%; P < 0.01; moderate certainty), HDL-C (MD -0.05 mmol/L, 95% CI -0.15 to 0.04; I² = 99%; p = 0.008; very low certainty) (Figure S10 and Table 2) and TG (MD -81.90 mg/dL, 95% CI -91.21 to -72.59; p < 0.01; very low certainty ) (Figure S11 and Table 2), but not in LDL-C (Figure S12 and Table 2).

IL-6, IL-8, TNF-α, and CRP were investigated in (six studies, n = 340), (three studies, n = 171), (four, n = 256), and (three, n = 218) trials, respectively. No significant changes were found in IL-6, IL-8, and CRP between CART and ST, but CART showed a greater reduction in TNF-α (SMD -0.89 pg/mL, 95% CI -1.70 to -0.08; I² = 89%; p = 0.03; low certainty) than ST (Figures S13, Figures S14, Figures S15, Figures S16 and Table 2). There were no significant changes in the effect estimate after the sensitivity analysis for Ergun et al. (2013) was done on IL-6, IL-8, and TNF-α. There were no significant changes in the effect estimate after the sensitivity analysis for Ligibel et al. (2008) was done on IL-6, IL-8, TNF-α, CRP, WC, BF,HC, BW and LEP.

ADPN and LEP were reported in (two studies, n = 120) and (four studies, n=236) trials, respectively. CART induced beneficial alterations in LEP (SMD -0.63 ng/mL, 95% CI -1.20 to -0.06; I² = 74%; p = 0.03; low certainty), but not in ADPN compared to ST (Figures S17, Figures S18 and Table 2). There were no significant changes in the effect estimate after the sensitivity analysis for Dieli-Conwright et al. (2022) was done on LEP.

NK cells, FA, SQ, and QoL were assessed in (two studies, n = 97), (four studies, n = 348), (four studies, n = 348) and (four studies, n = 356), respectively. CART more favorable changes in NK cells (SMD 0.42%, 95% CI 0.01 to 0.82; I² = 0%; p = 0.04; moderate certainty). Also, beneficial alterations were found in FA (SMD -0.98, 95% CI -1.85 to -0.11; I² = 92%; p = 0.03; very low certainty), SQ (SMD -1.40, 95% CI -2.50 to -0.30; I² = 87%; p = 0.01; low certainty), and QoL (SMD 2.94, 95% CI 0.46 to 5.41; I² = 98%; p = 0.02; very low certainty) scores compared to ST (Figure S19, Figure S20, Figure S21, Figure S22 and Table 2).

In the present review, for the first time to the best of our knowledge, evidence about the efficacy of CART on cardiometabolic risk factors and cancer-related indicators is provided. The main findings reveal that CART induces beneficial alterations in anthropometric characteristics, body composition, lipid metabolism, inflammation, adipokines, and cancer-related outcomes, such as fatigue, sleep, and quality of life in BC patients with overweight/obesity. Given that aerobic and resistance training alone have been documented as effective exercise modalities for provoking positive results in cardiometabolic health-related outcomes among people with excessive weight (Batrakoulis et al., 2022) and/or cancer (Kudiarasu et al., 2023; Yang et al., 2023), our findings suggest that CART may be considered as an effective exercise solution for women with BC and concurrent overweight/obesity commonly present with impaired cardiometabolic health (Simon et al., 2021). However, the present results should be taken into account with caution due to the small number of studies with small participant numbers and low-GRADE ratings included in the current meta-analysis.

The present meta-analysis provides insights into the positive role of CART on specific anthropometric characteristics, such as BMI and HC, but not BM, WC, and WHR in women with BC and concurrent overweight/obesity. However, visceral fat was not assessed and this also is an important category of variables that should be examined further in the future, given that this type of fat adversely affects metabolic health and promotes comorbidity among BC patients and survivors with excessive weight (Anwar et al., 2021). Interestingly, CART as a component of a multimodal lifestyle intervention promotes weight loss in BC survivors (Lake et al., 2022), which is not aligned with our results, given that no meaningful change was reported in BM. However, since women with BC and concurrent excess weight prone to have abdominal obesity linked to glucose metabolism dysregulation (Moore and Shah, 2020), further investigation is needed in this area to determine whether CART alone can induce a significant reduction in BM.

Our results also show considerable improvements in critical body composition markers, such as BF, FM, and FFM, which are in line with CART-induced adaptations reported in people with obesity, but without cancer (Batrakoulis et al., 2022). This is a vital outcome, considering the key role of the obesity epidemic in BC recurrence among those who successfully completed treatment (Acevedo et al., 2022). Likewise, previous research showed similar effects of CART on various anthropometric and body composition indices among BC patients and survivors (Joaquim et al., 2022). Ultimately, exercise training is more beneficial than usual care for increasing FFM in women with BC, both during and after treatment (Fraser et al., 2022). Taking this into account, the present findings corroborate the current evidence underlining the vital role of regular exercise training, with particular emphasis on muscle strengthening activities, regarding the physiological and functional importance of FFM in this cohort (Fraser et al., 2022). However, further high-quality trials are warranted to identify whether CART can elicit favorable changes in visceral adiposity that is associated with lower morbidity and mortality risks (Mulligan et al., 2019).

BC patients and survivors with concurrent overweight/obesity tend to demonstrate lipid metabolism impairments, enhancing the risk of developing CVD (Raychaudhuri et al., 2022). Thus, the relationship between lipid profile and obesity among BC survivors has been widely investigated (de Jesus et al., 2022; Okekunle et al., 2022; Vasseur and Guillaumond, 2022). According to the American Cancer Society guidelines, it is vital for cancer prevention and treatment to maintain a normal lipid profile, aiming to lower the likelihood of comorbidities (Rock et al., 2020). Importantly, the key role of lipid metabolism in promoting BC growth and progression has been documented, showing the strong relationship between obesity and BC (Blucher and Stadler, 2017). In this meta-analysis, CART elicited significant improvements in TC, HDL-C, and TG, but not in LDL-C. The present results support the current findings regarding the beneficial role of CART in improving blood lipids in BC patients (Kong and Gao, 2022). Such a remark cannot be explained here; however, the occurrence of obesity in conjunction with cancer may play some role in the simultaneous management of glucose and lipid homeostasis due to the presence of systemic inflammation (Roxburgh and McMillan, 2014). Noticeably, CART seems to be the optimal exercise solution for inducing favorable effects in lipid metabolism among people with BC and obesity (Kong and Gao, 2022), or obesity alone (Batrakoulis et al., 2022). Also, various traditional and alternative exercise modes appear effective for improving blood lipids in populations with impaired metabolic health and concurrent overweight/obesity (Al-Mhanna et al., 2023; Batrakoulis, 2022a; Batrakoulis, 2022b; Batrakoulis et al., 2021); however, additional studies examining these outcome measures among BC patients and survivors with overweight/obesity are necessary.

Obesity is associated with BC due to chronic adipose tissue inflammation, and thus BC patients with excess weight are likely to demonstrate high inflammatory markers (Kolb and Zhang, 2020). Interestingly, CART has been reported as an effective exercise training modality for improving the inflammatory profile in BC survivors (de Jesus Leite et al., 2018). In the present study, we detected significant CART-induced improvements in TNF-α, but not in IL-6, IL-8, and CRP. Such a substantial reduction in TNF-α is important, given that BC patients and survivors with overweight/obesity commonly present with several cardiometabolic health impairments linked to raised oxidative stress, diminished antioxidant capacity, and insulin dysregulation due to inflamed adipose tissue, altering the immune system (Roxburgh and McMillan, 2014; Simon et al., 2021). However, other inflammatory markers included in this meta-analysis did not exhibit significant changes following CART among BC patients and survivors with overweight/obesity. Hence, our results cannot provide clear evidence regarding the impact of CART on chronic inflammation in this cohort, and therefore further research in this area would be beneficial. Collectively, exercise training appears as a powerful non-pharmacological intervention for lowering circulating cytokines and inhibiting cancer recurrence in BC survivors (Zhou et al., 2022).

Considering that high circulating LEP levels increase the risk of tumor progression in cancer patients, while LEP resistance is common among individuals with obesity, exercise-induced reductions in LEP may be beneficial for BC patients and survivors with obesity (Perego et al., 2021). According to our results, CART showed a substantial reduction in LEP compared to ST. In general, data regarding the effects of CART on LEP among people with cancer and obesity are currently limited. However, a 6-month CART intervention improved various cardiometabolic health-related markers, including adipokines such as LEP and ADPN in middle-aged men with obesity (Brunelli et al., 2015). As for other exercise modes and their impact on LEP, conflicting results are present in the current literature regarding the effectiveness of long-term aerobic exercise. More specifically, aerobic exercise suggests dose-response favorable effects on LEP in premenopausal women at risk for BC (Sturgeon et al., 2016), but a 6-month aerobic-based training protocol did not exhibit a meaningful reduction in LEP among postmenopausal women at risk for BC (Khosravi et al., 2018). In summary, LEP has been documented as a vital mediator for the linkage between obesity and BC, promoting tumor initiation, development growth, and metastasis. That being said, future research on the potential role of CART interventions in circulating LEP levels may be necessary, since LEP is considered a key player in the novel therapeutic strategies for BC treatment (Atoum et al., 2020).

Given that ADPN is involved in glucose and energy homeostasis while being inversely associated with FM, individuals with obesity are commonly presented with low ADPN levels (Kadowaki and Yamauchi, 2005). Taking this into consideration, significant exercise-induced increases in ADPN levels may be critical for BC patients and survivors with a high BMI, since such favorable changes may improve body composition, affecting the risk of developing metastases (Perego et al., 2021). In this meta-analysis, CART did not suggest advantageous changes in ADPN relative to usual care. To date, relevant RCTs examining the role of ADPN in women with BC and obesity are scarce. However, a 4-week CART-like protocol showed positive alterations in ADPN among women with obesity, but without BC (Rejeki et al., 2023). Also, long-term aerobic exercise alone evokes a favorable elevation in ADPN levels while reducing BF in premenopausal women at risk for BC. Noticeably, these beneficial aerobic exercise-induced increases in ADPN were dependent on BF changes in this cohort (Sturgeon et al., 2016). Ultimately, ADPN is vital in both obesity and cancer, and thus exercise interventions suggesting significant increases in ADPN may considered as an important component of a multimodal treatment approach for BC patients and survivors with obesity (Perego et al., 2021).

Cancer-related FA has been reported as a very common side effect of BC caused by treatment affecting hormones related to fatigue and pain. Therefore, BC patients and survivors demonstrate a likelihood of developing various major mental health complications, such as anxiety, depression, and distress, resulting in reduced sleep and QoL (Cho and Hwang, 2021). Generally, there is a relationship among cancer-related FA, SQ, and QoL among BC patients and survivors. Interestingly, six in 10 of BC patients demonstrate major sleep problems linked to significant reductions in QoL and mood (Fortner et al., 2002). On the other hand, regular involvement in physical activity and exercise may help individuals with obesity improve all these health-related indicators (Bardwell and Ancoli-Israel, 2008; Mendelson et al., 2016). In the present review, CART exhibited significant improvements in cancer-related FA, SQ, and QoL relative to usual care, indicating that such a training modality may be a valuable adjunct therapy option in women with BC and excessive weight. Such beneficial alterations in critical cancer-related indices may also play an important role in adherence and behavioral regulation to exercise during and after treatment, since supervised exercise delivered in a real-world clinical setting should be a priority for patients, clinicians, and practitioners (Kirkham et al., 2018). However, it has been well documented that people with obesity are very likely to show mental health impairments due to body dissatisfaction (Gilyana et al., 2023) linked to sedentarism (Chekroud et al., 2018), resulting in high dropout rates when participating in regular structured exercise (Burgess et al., 2017). Collectively, exercise training seems to be a powerful weapon against poor QoL among BC patients and survivors, and therefore exercise prescription to this particular cohort may be effective for lowering FA, improving SQ, and increasing QoL (Chen et al., 2023). Given that both cancer and obesity adversely affect SQ (Chang and Chang, 2020) and QoL (Heidary et al., 2023; Taylor et al., 2013), the effectiveness of various exercise modes, including CART, is vital for women with BC and excess weight, since CART-induced adaptations and responses may mitigate potential depressive and anxiety symptoms, as well as sleep disturbances frequently present in this cohort before, during, and after treatment without reducing compliance rates compared to usual care. (Wang et al., 2023).

Considering that the combination of aerobic-based and muscle-strengthening activities is highly recommended for cancer patients and survivors (Campbell et al., 2019) as well as individuals with overweight/obesity (American College of Sports Medicine et al., 2021), further studies are urgently needed to investigate the optimal amount and intensity of CART for this cohort. Future trials should focus on the mechanisms behind the effectiveness of CART on cardiometabolic health and cancer-related indices as well as the association between CART and tumor growth. Also, studies examining the effects of CART on additional cardiovascular disease risk factors (e.g., glucose metabolism, blood pressure, and functional aerobic capacity) and mental health indicators (e.g., depression, anxiety, psychological distress, and mood) would support the current evidence. Furthermore, CART-like protocols should be investigated not only through supervised interventions conducted in a lab-based environment but also under real-world conditions, aiming to evaluate the practicability of CART among BC patients and survivors with overweight/obesity. Lastly, the potential role of CART in immunity among BC cancer patients and survivors also needs to be studied. Such a future approach may comprehend the relationship between CART and immune function as well as the connection between these immunological indicators and clinical benefits in this cohort.

The present review has several limitations and thus the findings should be taken into consideration with caution. Eligible studies exhibited inconsistency with regard to the training parameters implemented during the CART interventions, resulting in significant heterogeneity among the included trials. Our study demonstrates that beneficial CART-induced adaptations are existent principally among middle-aged (mean age: 54.0 ± 3.4 years) women. Hence, current outcomes cannot be generalized to men, other age and BMI groups among BC patients and survivors. Considering the outcome measures included in the present study, the role of CART in a wide spectrum of cardiometabolic health still remains unclear due to the lack of data in terms of glucose homeostasis, resting cardiovascular function, oxidative stress, and physical function. Moreover, we discovered substantial heterogeneity in some outcomes in our analysis, but we were unable to explain this due to limited trials. Despite conducting a sensitivity analysis to explore the influence of performance bias and detection bias on the outcomes, in the majority of cases, there were no changes in the estimated effects. This may be attributed to inadequate sample size and biases associated with performance and detection.

The present systematic review and meta-analysis delivers critical outcomes regarding the implementation of CART for BC patients and survivors with concurrent overweight/obesity as an adjunct component of a comprehensive therapy plan. The findings reveal clear evidence that CART has a favorable effect on cardiometabolic health and cancer-related indicators, such as anthropometric characteristics, body composition, lipid homeostasis, inflammation, adipokines, fatigue, sleep, and QoL in BC patients and survivors with concurrent overweight/obesity during and after treatment. More trials with robust methodological design are needed to investigate the dose-response relationship, training parameters configuration, and mechanisms behind these beneficial alterations. This meta-analysis also highlights the rationale for further high-quality RCTs to examine additional outcome measures related to cardiometabolic and mental health, aiming to support the present CART-induced effects for BC patients and survivors with concurrent overweight/obesity.