Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities.

Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes. This is most clearly established for estrogen receptor-positive breast cancer, with the relationship in triple-negative and human epidermal growth factor receptor 2-positive subtypes less well established. A range of biologic mechanisms that may underlie this association has been identified. Weight loss and lifestyle interventions, as well as metformin and other obesity-targeted therapies, are promising avenues that require further study. Conclusion Obesity is associated with inferior survival in breast cancer. Understanding the nature and mechanisms of this effect provides an important opportunity for interventions to improve the diagnosis, treatment, and outcomes of obese patients with breast cancer.

[1]  M. Climent,et al.  Twelve-Month Estrogen Levels in Premenopausal Women With Hormone Receptor-Positive Breast Cancer Receiving Adjuvant Triptorelin Plus Exemestane or Tamoxifen in the Suppression of Ovarian Function Trial (SOFT): The SOFT-EST Substudy. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Gary H Lyman,et al.  American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  L. Hou,et al.  Abstract CT043: Low-fat dietary pattern and breast cancer mortality in the Women's Health Initiative (WHI) randomized trial , 2016 .

[4]  J. Pierce,et al.  A pooled analysis of post‐diagnosis lifestyle factors in association with late estrogen‐receptor–positive breast cancer prognosis , 2016, International journal of cancer.

[5]  A. Chagpar,et al.  Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  P. Goodwin,et al.  Obesity and Breast Cancer Outcomes: How Much Evidence Is Needed to Change Practice? , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D. Amadori,et al.  Abstract PD2-01: Randomized phase 3 trial of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor positive, node positive early breast cancer: Final efficacy and safety results of the femara versus anastrozole clinical evaluation (Face) trial , 2016 .

[8]  E. Negri,et al.  Risk of severe cardiotoxicity following treatment with trastuzumab: a meta-analysis of randomized and cohort studies of 29,000 women with breast cancer , 2016, Internal and Emergency Medicine.

[9]  R. Rouzier,et al.  Beyond Axillary Lymph Node Metastasis, BMI and Menopausal Status Are Prognostic Determinants for Triple-Negative Breast Cancer Treated by Neoadjuvant Chemotherapy , 2015, PloS one.

[10]  M. Bracken,et al.  Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis. , 2015, Journal of the National Cancer Institute.

[11]  S. Hursting,et al.  Obesity and cancer: mechanistic insights from transdisciplinary studies. , 2015, Endocrine-related cancer.

[12]  G. Tang,et al.  Body Mass Index at Diagnosis and Breast Cancer Survival Prognosis in Clinical Trial Populations from NRG Oncology/NSABP B-30, B-31, B-34, and B-38 , 2015, Cancer Epidemiology, Biomarkers & Prevention.

[13]  X. Pi-Sunyer Liraglutide in Weight Management. , 2015, The New England journal of medicine.

[14]  M. Beckmann,et al.  The influence of obesity on survival in early, high-risk breast cancer: results from the randomized SUCCESS A trial , 2015, Breast Cancer Research.

[15]  D. Berry,et al.  Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance). , 2015, Journal of the National Cancer Institute.

[16]  G. Colditz,et al.  Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  D. Cromwell,et al.  Socioeconomic deprivation and inpatient complication rates following mastectomy and breast reconstruction surgery , 2015, The British journal of surgery.

[18]  E. Perez,et al.  Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  A. Astrup,et al.  A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. , 2015, The New England journal of medicine.

[20]  S. Jiralerspong,et al.  Metformin in breast cancer - an evolving mystery , 2015, Breast Cancer Research.

[21]  Keda Yu,et al.  Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women , 2015, PloS one.

[22]  I. Shureiqi,et al.  Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer , 2015, Cancer Prevention Research.

[23]  R. Chlebowski,et al.  Abstract S5-08: Final survival analysis from the randomized Women's Intervention Nutrition Study (WINS) evaluating dietary intervention as adjuvant breast cancer therapy , 2015 .

[24]  A. Giordano,et al.  Metformin and breast cancer: basic knowledge in clinical context. , 2015, Cancer treatment reviews.

[25]  A. Harris,et al.  Neoadjuvant Window Studies of Metformin and Biomarker Development for Drugs Targeting Cancer Metabolism. , 2015, Journal of the National Cancer Institute. Monographs.

[26]  F. Montemurro,et al.  Adjuvant ovarian suppression in premenopausal breast cancer. , 2015, The New England journal of medicine.

[27]  Bingshu E. Chen,et al.  Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32. , 2015, Journal of the National Cancer Institute.

[28]  A. Schneeweiss,et al.  Impact of body mass index on neoadjuvant treatment outcome: a pooled analysis of eight prospective neoadjuvant breast cancer trials , 2015, Breast Cancer Research and Treatment.

[29]  C. Hudis,et al.  Obesity and cancer: local and systemic mechanisms. , 2015, Annual review of medicine.

[30]  P. Goodwin,et al.  Impact of the obesity epidemic on cancer. , 2015, Annual review of medicine.

[31]  Kristian Thorlund,et al.  Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. , 2014, JAMA.

[32]  D. Decker,et al.  Obesity and NonAdherence Correlate with Elevated Serum Estradiol Levels in Postmenopausal Women Receiving Adjuvant Aromatase Inhibitor Therapy , 2014, The breast journal.

[33]  W. Demark-Wahnefried,et al.  Weight loss intervention trials in women with breast cancer: a systematic review , 2014, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[34]  Alan D. Lopez,et al.  Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013 , 2014, The Lancet.

[35]  D. Porter,et al.  Effect of obesity on aromatase inhibitor efficacy in postmenopausal, hormone receptor-positive breast cancer: a systematic review , 2014, Breast Cancer Research and Treatment.

[36]  D. Clegg,et al.  Obesity and cancer—mechanisms underlying tumour progression and recurrence , 2014, Nature Reviews Endocrinology.

[37]  G. Pond,et al.  Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  A. Giobbie-Hurder,et al.  Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. , 2014, The New England journal of medicine.

[39]  M. Ellis,et al.  Body mass index, diabetes, and triple-negative breast cancer prognosis , 2014, Breast Cancer Research and Treatment.

[40]  S. Zhong,et al.  Association between physical activity and mortality in breast cancer: a meta-analysis of cohort studies , 2014, European Journal of Epidemiology.

[41]  R. Gray,et al.  Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials. , 2014 .

[42]  J. Fischer,et al.  A 30-day risk assessment of mastectomy alone compared to immediate breast reconstruction (IBR) , 2014, Journal of plastic surgery and hand surgery.

[43]  A. McTiernan,et al.  Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[44]  J. Fischer,et al.  Venous Thromboembolism Risk in Mastectomy and Immediate Breast Reconstruction: Analysis of the 2005 to 2011 American College of Surgeons National Surgical Quality Improvement Program Data Sets , 2014, Plastic and reconstructive surgery.

[45]  K. Flegal,et al.  Prevalence of childhood and adult obesity in the United States, 2011-2012. , 2014, JAMA.

[46]  C. Perou,et al.  Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer , 2013, Breast Cancer Research and Treatment.

[47]  J. Mackey,et al.  Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis , 2013, Breast Cancer Research.

[48]  P. Pelicci,et al.  Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients. , 2013, European journal of cancer.

[49]  Suhail K. Kanchwala,et al.  Impact of obesity on outcomes in breast reconstruction: analysis of 15,937 patients from the ACS-NSQIP datasets. , 2013, Journal of the American College of Surgeons.

[50]  G. Hortobagyi,et al.  Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[51]  J. Fischer,et al.  Breast Reconstruction in the Morbidly Obese Patient: Assessment of 30-Day Complications Using the 2005 to 2010 National Surgical Quality Improvement Program Data Sets , 2013, Plastic and reconstructive surgery.

[52]  M. Gnant,et al.  Impact of body mass index on estradiol depletion by aromatase inhibitors in postmenopausal women with early breast cancer , 2013, British Journal of Cancer.

[53]  Q. Chu,et al.  Does obesity have an effect on outcomes in triple-negative breast cancer? , 2013, The Journal of surgical research.

[54]  G. Lyman,et al.  Chemotherapy dosing in overweight and obese patients with cancer , 2013, Nature Reviews Clinical Oncology.

[55]  R. Greil,et al.  The predictive impact of body mass index on the efficacy of extended adjuvant endocrine treatment with anastrozole in postmenopausal patients with breast cancer: an analysis of the randomised ABCSG-6a trial , 2013, British Journal of Cancer.

[56]  E. Perez,et al.  Effect of body mass index on tumor characteristics and disease‐free survival in patients from the HER2‐positive adjuvant trastuzumab trial N9831 , 2013, Cancer.

[57]  M. Irwin,et al.  Weight Loss Intervention for Breast Cancer Survivors: A Systematic Review , 2013, Current Breast Cancer Reports.

[58]  B. Newman,et al.  Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. , 2013, The Lancet. Oncology.

[59]  P. Hadji,et al.  Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole , 2013, Journal of Cancer Research and Clinical Oncology.

[60]  Dongfeng Zhang,et al.  Physical activity and risk of breast cancer: a meta-analysis of prospective studies , 2013, Breast Cancer Research and Treatment.

[61]  E. Perez,et al.  Obesity at diagnosis is associated with inferior outcomes in hormone receptor‐positive operable breast cancer , 2012, Cancer.

[62]  J. Forbes,et al.  Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[63]  C. Diorio,et al.  Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels , 2012, Breast Cancer Research and Treatment.

[64]  Jiang He,et al.  Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. , 2012, American journal of epidemiology.

[65]  G. Hortobagyi,et al.  Impact of body mass index on survival outcome among women with early stage triple-negative breast cancer. , 2012, Clinical breast cancer.

[66]  N. Parekh,et al.  Obesity in cancer survival. , 2012, Annual review of nutrition.

[67]  M. Dowsett,et al.  Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  Saroj Niraula,et al.  Metformin in cancer: translational challenges. , 2012, Journal of molecular endocrinology.

[69]  C. Perou,et al.  Dietary Energy Balance Modulates Epithelial-to-Mesenchymal Transition and Tumor Progression in Murine Claudin-Low and Basal-like Mammary Tumor Models , 2012, Cancer Prevention Research.

[70]  P. Goodwin,et al.  Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis , 2012, Breast Cancer Research and Treatment.

[71]  G. Rosner,et al.  Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[72]  P. Goodwin,et al.  Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  F. Berrino,et al.  Lifestyle and Breast Cancer Recurrences: The DIANA-5 Trial , 2012 .

[74]  Nutrition and physical activity guidelines for cancer survivors , 2012, CA: a cancer journal for clinicians.

[75]  M. Pierobon,et al.  Obesity as a risk factor for triple-negative breast cancers: a systematic review and meta-analysis , 2012, Breast Cancer Research and Treatment.

[76]  S. Edge,et al.  Impact of body mass index on clinical outcomes in triple‐negative breast cancer , 2011, Cancer.

[77]  R. Greil,et al.  Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  P. Lønning The potency and clinical efficacy of aromatase inhibitors across the breast cancer continuum , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[79]  M. Ewertz,et al.  Effect of obesity on prognosis after early-stage breast cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  M. Beckmann,et al.  The German SUCCESS C Study – The First European Lifestyle Study on Breast Cancer , 2010, Breast Care.

[81]  J. Cuzick,et al.  Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[82]  M. Coory,et al.  Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis , 2010, Breast Cancer Research and Treatment.

[83]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2008. , 2010, JAMA.

[84]  D. Nieman,et al.  Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates , 2010 .

[85]  X. Shu,et al.  Obesity and weight change in relation to breast cancer survival , 2010, Breast Cancer Research and Treatment.

[86]  Donald A Williamson,et al.  Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. , 2009, The New England journal of medicine.

[87]  Funda Meric-Bernstam,et al.  Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[88]  P. Goodwin,et al.  Metformin in breast cancer: time for action. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[89]  J. Pierce Diet and breast cancer prognosis: making sense of the Women's Healthy Eating and Living and Women's Intervention Nutrition Study trials , 2009, Current opinion in obstetrics & gynecology.

[90]  A. Wolk,et al.  Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—A meta‐analysis , 2009, International journal of cancer.

[91]  P. Loehrer Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study , 2008 .

[92]  Arne Astrup,et al.  Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. , 2008, The New England journal of medicine.

[93]  B. Asselain,et al.  Is obesity an independent prognosis factor in woman breast cancer? , 2008, Breast Cancer Research and Treatment.

[94]  A. Bhatnagar The discovery and mechanism of action of letrozole , 2007, Breast Cancer Research and Treatment.

[95]  Loki Natarajan,et al.  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. , 2007, JAMA.

[96]  D. Wickerham,et al.  Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer , 2006, Breast Cancer Research and Treatment.

[97]  E. Mamounas,et al.  Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. , 2003, Journal of the National Cancer Institute.

[98]  A. McTiernan,et al.  Weight loss in breast cancer patient management. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  B. Hoffman,et al.  Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.