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Effects of lifestyle modification after breast cancer treatment: a systematic review protocol

  • Maicon Falavigna1, 2, 3,
  • Karine Margarites Lima1, 3,
  • Juliana Giacomazzi4,
  • Diego d’Avila Paskulin3, 4,
  • Luciano Serpa Hammes1,
  • Rodrigo Antonini Ribeiro1, 3 and
  • Daniela Dornelles Rosa1, 5Email author
Systematic Reviews20143:72

DOI: 10.1186/2046-4053-3-72

Received: 25 March 2014

Accepted: 17 June 2014

Published: 5 July 2014

Abstract

Background

There is no consensus in the literature regarding the effectiveness of lifestyle modification interventions, including recommendations about specific diet or exercise program for patients with breast cancer. Diet interventions and regular physical activity may reduce the risk of breast cancer and its recurrence. The primary aim of our study is to evaluate the effects of different lifestyle modification interventions (diet and physical activity) in the survival of patients with stages I to III breast cancer after treatment.

Methods/design

This review will be conducted according to the Cochrane Handbook for Systematic Reviews of Intervention and will be reported following the PRISMA statement recommendations. CENTRAL, MEDLINE and EMBASE databases will be searched for peer-reviewed literature. Randomized controlled trials of diet, exercise, or both, compared with usual care, after treatment of breast cancer stage I to III will be included in the systematic review. Two authors will independently screen titles and abstracts of studies for potential eligibility. Data will be combined using random-effect meta-analysis models with restricted maximum-likelihood as variance estimator, and will be presented as relative risk or standardized mean difference with 95% CI. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and summary of findings tables will be presented for patient important outcomes.

Discussion

Our study may improve the current understanding of the role that lifestyle-modifiable factors can play in saving or prolonging the lives of women who have been treated for breast cancer, and also on modifying their quality of life.

Systematic review registration

The review has been registered with PROSPERO (registration number CRD42014008743).

Keywords

Breast cancer Lifestyle interventions Exercise Diet Physical activity Systematic review Adjuvant chemotherapy

Background

High body mass index (BMI) is well established as a risk factor for the development of breast cancer, especially for post-menopausal women [1, 2]. More than half of women diagnosed with breast cancer experience an increase in body weight associated with chemotherapy and treatment-related menopause [3]. Additionally, there is evidence that overweight or obese women and women with weight gain after diagnosis have an increased risk of disease recurrence and death compared to eutrophic women [48]. Women with a high body mass index have double the risk of five-year breast cancer recurrence and a 60% increased risk of death over 10 years in comparison to women with a normal BMI [6].

Dietary energy restriction reduces body weight, promoting a positive effect on psychological wellbeing in obese women and breast cancer survivors [911]. Weight loss interventions that reduce the dietary intake of fat to between 18 and 25% of total calories can also evoke a significant reduction in serum estrogen levels in pre- and post-menopausal women [12]. A diet rich in vegetables and fruits may decrease the risk of breast cancer and a diet high in total fat may increase the risk [13]. However, evidence of an association between a diet high in vegetables and fruit and low in total fat, and prevention of cancer progression has been conflicting in epidemiological studies [8, 1421].

Regular physical activity can help to control body weight and is known to reduce the risk of breast cancer [2225]. Additional studies also suggest that it can halve the risk of death in breast cancer patients [26, 27]. Regular physical activity can also have a positive effect on psychological health status and quality of life in breast cancer survivors that could enhance immune function through the normalization of stress hormone levels [2830].

There is no consensus in the literature regarding the effectiveness of lifestyle modification interventions, including recommendations about a specific diet or exercise program for patients with breast cancer. The results of observational studies evaluating lifestyle modification and breast cancer recurrence have been mixed. In addition, the randomized clinical trials that have been published are inconclusive [31, 32] and there are no recent systematic reviews assessing this topic. Therefore, the primary aim of our study is to evaluate the effects of different lifestyle modification interventions (diet and physical activity) in the survival and disease-free survival of patients with stages I to III breast cancer after treatment.

Methods/design

We will conduct this review according to the Cochrane Handbook for Systematic Reviews of Intervention [33] and we will report data following the PRISMA statement recommendations [34].We will assess the quality of evidence for each outcome according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework [35, 36]. The review has been registered with PROSPERO (registration number: CRD42014008743).

Inclusion criteria

The type of studies included will be randomized controlled trials of diet, exercise, or both, compared to usual care, after treatment of breast cancer stage I to III. The participants to be included will be women with invasive breast cancer, stage I to III, who were treated with curative intent in the previous five years, with no evidence of disease recurrence. The types of interventions considered will be as follows: (1) dietary advice delivered through group meetings, by telephone calls, or by mail correspondence; (2) individualized dietary counseling; (3) prescription of a specific diet, such as a calorie-restricted diet; (4) any type of exercise counseling that encouraged women to engage in regular recreational exercises, such as walking, jogging or sports; and (5) structured or individualized exercise programs or interventions in which women participated in supervised exercise sessions.

Types of outcomes

The primary outcomes of the systematic review are overall survival and disease-free survival (five years post treatment and at the study maximum follow-up period for both outcomes).

We will also evaluate the following secondary outcomes: (1) diet and exercise related modifiable risk factors (weight, BMI, waist-hip ratio and body fat); (2) mediators and other metabolic factors potentially associated with breast cancer (adiponectin, leptin, IGF-1, IGFBP1, IGFBP2, insulin, C-peptide, HOMA-IR, estradiol, testosterone and SHBG); (3) quality of life; and (4) adverse events (such as exercise-induced injuries or side effects of very low-calorie diets).

Search strategy and sources

The following electronic databases will be searched for peer-reviewed literature: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. The search strategy was developed based on search strategies from published filters and systematic reviews [3739], and is detailed in Additional file 1.

In addition, we will perform an electronic search for ongoing studies at ClinicalTrials.gov and hand searches of reference lists of included articles and of the proceedings of the following major conferences: American Society of Clinical Oncology (2010 to 2014), San Antonio Breast Cancer Symposium (2010 to 2014), European Society of Medical Oncology (2010 to 2014), Society for Integrative Oncology (2010 to 2014), American Association for Cancer Research (AACR) (2010 to 2014), and World Cancer Research Fund International (2010 to 2014).

Data collection and analysis

Study selection

Two authors will independently screen titles and abstracts of studies for potential eligibility. Full texts of potentially eligible studies will be retrieved and two authors will independently apply inclusion criteria to identify relevant studies to be included in the review. Disagreement will be resolved through discussion; if necessary, a third reviewer will be involved. We will provide a table with characteristics of included studies, and another table of excluded studies with reasons for their exclusion, in the final review.

Data extraction and management

Two reviewers will independently extract data using a standardized form. The following data will be abstracted: (1) characteristics of trial participants (age, ethnicity, BMI, weight, body fat, waist-hip ratio, breast cancer stage, treatment, and breast cancer biological subtype); (2) type of intervention (such as type of diet or exercise program); (3) outcome measures and their definition according to individual studies; and (4) methodological quality of individual studies, according to the Cochrane Handbook for Systematic Reviews [33].

Disagreement will be resolved through discussion. When quantitative data is not reported, approximate values will be estimate from the figures or calculated from proportions.

Quality assessment

The risk of bias of all eligible studies will be assessed independently by two reviewers using the Cochrane Collaboration’s Risk of Bias tool [33]. Disagreement will be resolved through discussion. Overall quality of evidence will be assessed using GRADE by a GRADE working group member and will checked by a second reviewer [35, 36].

Data synthesis and presentation

Data will be combined using random-effect meta-analysis models, with restricted maximum-likelihood (REML) variance estimator and presented as relative risks (RR) or standardized mean difference (SMD) with 95% confidence intervals (CI). All analyses will be performed using the R software, version 3.0.2 (R: A Language and Environment for Statistical Computing, Vienna, Austria); packages ‘meta’ version 3.0-1 (meta: Meta-Analysis with R. R package version) and ‘metafor’ version 1.9-1 (Conducting meta-analyses in R with the metafor package) [40, 41]. GRADE summary of findings tables will be presented for the primary outcomes [42, 43].

Heterogeneity

We will assess statistical heterogeneity in each meta-analysis using the I2 statistics. We will regard heterogeneity as substantial if the I2 is greater than 50%. Heterogeneity will be explored through pre-specified subgroup and sensitivity analysis as presented below.

Publication bias

If there are 10 or more studies in the meta-analysis we will investigate publication bias using funnel plots and Egger`s test [44]. If asymmetry is suggested by a visual assessment, we will perform exploratory analyses to investigate and adjust it (trim and fill analysis) [45].

Missing data

For included studies, we will note levels of attrition. We will explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we will carry out analyses, as far as possible, on an intention-to-treat basis, in that we will attempt to include all participants randomized to each group in the analyses, and all participants will be analyzed in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial will be the number randomized minus the number of participants whose outcomes are known to be missing.

Sensitivity analysis

In order to identify potential sources of heterogeneity, we will perform the following subgroup analysis: (1) type of intervention (diet, exercise, or both); (2) breast cancer treatment (adjuvant versus neoadjuvant); (3) tumor stage (according to AJCC) [46]; (4) subtypes of breast cancer according to immunohistochemistry (positivity for HR and/or HER2); (5) Mean follow-up period (≥24 months) and (6) risk of bias of included studies). Additionally, meta-regression will be performed according to the mean follow-up period of the included studies.

Discussion

The results of this study may improve our understanding of the role that lifestyle-modifiable factors can play in saving or prolonging the lives of women who have been treated for breast cancer, and also on modifying their quality of life. Additionally, this study will provide evidence that may be used for the development of recommendations in guidelines of breast cancer treatment.

Abbreviations

AJCC: 

American Joint Committee on Cancer

BMI: 

Body mass index

HER2: 

Human epidermal growth factor receptor 2

HOMA-IR: 

Homeostasis model assessment-estimated insulin resistance

HR: 

Hormone receptor

IGF1: 

Insulin-like growth factor 1

IGFBP1: 

Insulin-like growth factor-binding protein 1

IGFBP2: 

Insulin-like growth factor-binding protein 2

SHBG: 

Sex hormone-binding globulin.

Declarations

Acknowledgements

The publication of this protocol was supported by funding from Hospital Moinhos de Vento, Porto Alegre, Brazil. Hospital Moinhos de Vento is a private non-profit institution. There were no further funding sources.

Authors’ Affiliations

(1)
Institute for Education and Research, Hospital Moinhos de Vento
(2)
Department of Clinical Epidemiology and Biostatistics, McMaster University
(3)
Postgraduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul
(4)
Molecular Biology Laboratory, Santa Casa de Misericórdia de Porto Alegre
(5)
Oncology Unit, Hospital Moinhos de Vento, Hospital Moinhos de Vento

References

  1. Cheraghi Z, Poorolajal J, Hashem T, Esmailnasab N, Doosti Irani A: Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis. PLoS One. 2012, 7: e51446-View ArticlePubMedPubMed CentralGoogle Scholar
  2. Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A: Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev. 2014, 36: 114-136.View ArticlePubMedPubMed CentralGoogle Scholar
  3. Holmes MD, Kroenke CH: Beyond treatment: lifestyle choices after breast cancer to enhance quality of life and survival. Womens Health Issues. 2004, 14: 11-13.View ArticlePubMedGoogle Scholar
  4. Camoriano JK, Loprinzi CL, Ingle JN, Therneau TM, Krook JE, Veeder MH: Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. Am J Clin Oncol. 1990, 8: 1327-1334.Google Scholar
  5. Chlebowski RT, Aiello E, McTiernan A: Weight loss in breast cancer patient management. Am J Clin Oncol. 2002, 20: 1128-1143.View ArticleGoogle Scholar
  6. Goodwin PJ, Boyd NF: Body size and breast cancer prognosis: a critical review of the evidence. Breast Cancer Res Treat. 1990, 16: 205-214.View ArticlePubMedGoogle Scholar
  7. Schapira DV, Kumar NB, Lyman GH, Cox CE: Obesity and body fat distribution and breast cancer prognosis. Cancer. 1991, 67: 523-528.View ArticlePubMedGoogle Scholar
  8. Zumoff B, Gorzynski JG, Katz JL, Weiner H, Levin J, Holland J, Fukushima DK: Nonobesity at the time of mastectomy is highly predictive of 10-year disease-free survival in women with breast cancer. Anticancer Res. 1982, 2: 59-62.PubMedGoogle Scholar
  9. Djuric Z, DiLaura NM, Jenkins I, Darga L, Jen CK, Mood D, Bradley E, Hryniuk WM: Combining weight-loss counseling with the weight watchers plan for obese breast cancer survivors. Obes Res. 2002, 10: 657-665.View ArticlePubMedGoogle Scholar
  10. Jen KL, Djuric Z, DiLaura NM, Buison A, Redd JN, Maranci V, Hryniuk WM: Improvement of metabolism among obese breast cancer survivors in differing weight loss regimens. Obes Res. 2004, 12: 306-312.View ArticlePubMedGoogle Scholar
  11. Kaukua J, Pekkarinen T, Sane T, Mustajoki P: Health-related quality of life in obese outpatients losing weight with very-low-energy diet and behaviour modification: a 2-y follow-up study. Int J Obes Relat Metab Disord. 2003, 27: 1072-1080.View ArticlePubMedGoogle Scholar
  12. Wu AH, Pike MC, Stram DO: Meta-analysis: dietary fat intake, serum estrogen levels, and the risk of breast cancer. J Natl Cancer Inst. 1999, 91: 529-534.View ArticlePubMedGoogle Scholar
  13. Wiseman M: The second world cancer research fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proc Nutr Soc. 2008, 67: 253-256.View ArticlePubMedGoogle Scholar
  14. Beasley JM, Newcomb PA, Trentham-Dietz A, Hampton JM, Bersch AJ, Passarelli MN, Holick CN, Titus-Ernstoff L, Egan KM, Holmes MD, Willett WC: Post-diagnosis dietary factors and survival after invasive breast cancer. Breast Cancer Res Treat. 2011, 128: 229-236.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Holm LE, Nordevang E, Hjalmar ML, Lidbrink E, Callmer E, Nilsson B: Treatment failure and dietary habits in women with breast cancer. J Natl Cancer Inst. 1993, 85: 32-36.View ArticlePubMedGoogle Scholar
  16. Ingram D: Diet and subsequent survival in women with breast cancer. Br J Cancer. 1994, 69: 592-595.View ArticlePubMedPubMed CentralGoogle Scholar
  17. Jain M, Miller AB, To T: Premorbid diet and the prognosis of women with breast cancer. J Natl Cancer Inst. 1994, 86: 1390-1397.View ArticlePubMedGoogle Scholar
  18. Kroenke CH, Fung TT, Hu FB, Holmes MD: Dietary patterns and survival after breast cancer diagnosis. Am J Clin Oncol. 2005, 23: 9295-9303.View ArticleGoogle Scholar
  19. Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy WK, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CL: Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. Am J Clin Oncol. 2007, 25: 2345-2351.View ArticleGoogle Scholar
  20. Rock CL, Demark-Wahnefried W: Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. Am J Clin Oncol. 2002, 20: 3302-3316.View ArticleGoogle Scholar
  21. Zhang S, Folsom AR, Sellers TA, Kushi LH, Potter JD: Better breast cancer survival for postmenopausal women who are less overweight and eat less fat. Cancer. 1995, 76: 275-283.View ArticlePubMedGoogle Scholar
  22. Gao Y, Huang YB, Liu XO, Chen C, Dai HJ, Song FJ, Wang J, Chen KX, Wang YG: Tea consumption, alcohol drinking and physical activity associations with breast cancer risk among chinese females: a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2013, 14: 7543-7550.View ArticlePubMedGoogle Scholar
  23. Moradi T, Adami HO, Bergstrom R, Gridley G, Wolk A, Gerhardsson M, Dosemeci M, Nyren O: Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden. Cancer Causes Contro. 1999, 10: 423-430.View ArticleGoogle Scholar
  24. Wu Y, Zhang D, Kang S: Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013, 137: 869-882.View ArticlePubMedGoogle Scholar
  25. Rockhill B, Willett WC, Hunter DJ, Manson JE, Hankinson SE, Colditz GA: A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med. 1999, 159: 2290-2296.View ArticlePubMedGoogle Scholar
  26. Ibrahim EM, Al-Homaidh A: Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. 2011, 28: 753-765.View ArticlePubMedGoogle Scholar
  27. Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA: Physical activity and survival after breast cancer diagnosis. JAMA. 2005, 293: 2479-2486.View ArticlePubMedGoogle Scholar
  28. Blanchard CM, Courneya KS, Rodgers WM, Murnaghan DM: Determinants of exercise intention and behavior in survivors of breast and prostate cancer: an application of the theory of planned behavior. Cancer Nurs. 2002, 25: 88-95.View ArticlePubMedGoogle Scholar
  29. Campbell A, Mutrie N, White F, McGuire F, Kearney N: A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment. Eur J Oncol Nurs. 2005, 9: 56-63.View ArticlePubMedGoogle Scholar
  30. Segar ML, Katch VL, Roth RS, Garcia AW, Portner TI, Glickman SG, Haslanger S, Wilkins EG: The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors. Oncol Nurs Forum. 1998, 25: 107-113.PubMedGoogle Scholar
  31. Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson RW, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML: Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007, 298: 289-298.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Blackburn GL, Wang KA: Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS). Am J Clin Nutr. 2007, 86: s878-s881.PubMedGoogle Scholar
  33. Higgins JPT, Green S: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. 2011, The Cochrane Collaboration,http://www.cochrane-handbook.org,Google Scholar
  34. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009, 339: b2700-View ArticlePubMedPubMed CentralGoogle Scholar
  35. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, Vist GE, Falck-Ytter Y, Meerpohl J, Norris S, Guyatt GH: GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011, 64: 401-406.View ArticlePubMedGoogle Scholar
  36. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ, Group GW: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008, 336: 924-926.View ArticlePubMedPubMed CentralGoogle Scholar
  37. Scottish Intercollegiate Guidelines Network: Search Filters. [http://www.sign.ac.uk/methodology/filters.html]
  38. Cochrane Breast Cancer Group: Cochrane Breast Cancer Group’s module. [http://onlinelibrary.wiley.com/o/cochrane/clabout/articles/BREASTCA/frame.html]
  39. Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roque IFM, Richter B, Mauricio D: Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev. 2008, CD003054-Google Scholar
  40. Schwarzer G: Package ‘meta’: Meta-Analysis with R. Book Package ‘meta’: Meta-Analysis with R. 2013, City: The R Foundation for Statistical Computing,http://CRAN.R-project.org/package=meta,Google Scholar
  41. Viechtbauer W: Conducting meta-analyses in R with the metafor package. J Stat Software. 2010, 36: 1-48.View ArticleGoogle Scholar
  42. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, Brozek J, Norris S, Meerpohl J, Djulbegovic B, Alonso-Coello P, Post PN, Busse JW, Glasziou P, Christensen R, Schünemann HJ: GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. J Clin Epidemiol. 2013, 66: 158-172.View ArticlePubMedGoogle Scholar
  43. Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, Johnston BC, Karanicolas P, Akl EA, Vist G, Kunz R, Brozek J, Kupper LL, Martin SL, Meerpohl JJ, Alonso-Coello P, Christensen R, Schunemann HJ: GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles-continuous outcomes. J Clin Epidemiol. 2013, 66: 173-183.View ArticlePubMedGoogle Scholar
  44. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997, 315: 629-634.View ArticlePubMedPubMed CentralGoogle Scholar
  45. Duval S, Tweedie R: Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000, 56: 455-463.View ArticlePubMedGoogle Scholar
  46. AJCC Cancer Staging Manual. Edited by: Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. 2010, New York: Springer-Verlag, 347-7Google Scholar

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© Falavigna et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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