Body Mass Index and Weight Change in Patients With HER2-Positive Early Breast Cancer: Exploratory Analysis of the ALTTO BIG 2-06 Trial

View More View Less
  • 1 Department of Hemato-Oncology, CISSS Montérégie Centre/Hôpital Charles Le Moyne, Université de Sherbrooke, Greenfield Park, Quebec, Canada;
  • 2 Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy;
  • 3 Frontier Science, Kingussie, United Kingdom;
  • 4 Department of Medicine, Camargo Cancer Center, Sao Paulo, Brazil;
  • 5 Institut Jules Bordet and L’Université Libre de Bruxelles (U.L.B.), Brussels, Belgium;
  • 6 Breast International Group, Brussels, Belgium;
  • 7 National Cancer Institute, Bethesda, Maryland;
  • 8 Novartis Pharma AG, Basel, Switzerland;
  • 9 Mayo Clinic, Jacksonville, Florida;
  • 10 University of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany;
  • 11 Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium; and
  • 12 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Restricted access

Background: The association between obesity and prognosis in HER2-positive early breast cancer remains unclear, with limited data available. This study aimed to determine the impact of body mass index (BMI) at baseline and weight change after 2 years on outcomes of patients with HER2-positive early breast cancer. Methods: ALTTO was a randomized phase III trial in patients with HER2-positive early breast cancer. BMI was collected at randomization and 2 years after. WHO BMI categories were used: underweight, <18.5 kg/m2; normal weight, 18.5 to <25 kg/m2; overweight, ≥25 to <30 kg/m2; and obese ≥30 kg/m2. A weight change from baseline of ≥5.0% and ≤5.0% was categorized as weight gain and weight loss. The impact of BMI at randomization and of weight change on disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were investigated with multivariate analyses, adjusting for baseline patients and tumor characteristics. Results: A total of 8,381 patients were included: 187 (2.2%), 3,797 (45.3%), 2,690 (32.1%), and 1,707 (20.4%) were underweight, normal weight, overweight, and obese at baseline, respectively. Compared with normal weight, being obese at randomization was associated with a significantly worse DDFS (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.04–1.50) and OS (aHR, 1.27; 95% CI, 1.01–1.60), but no significant difference in DFS (aHR, 1.14; 95% CI, 0.97–1.32). Weight loss ≥5.0% at 2 years after randomization was associated with significantly poorer DFS (aHR, 1.34; 95% CI, 1.05–1.71), DDFS (aHR, 1.46; 95% CI, 1.07–1.98), and OS (aHR, 1.83; 95% CI, 1.18–2.84). Hormone receptor and menopausal status but not anti-HER2 treatment type influenced outcomes. Toxicities were more frequent in obese patients. Conclusions: In patients with HER2-positive early breast cancer, obesity at baseline is a poor prognostic factor. Weight loss during treatment and follow-up negatively impacts clinical outcomes. Dietary counseling should be part of survivorship care programs.

These authors are co-last authors.

Submitted April 10, 2020; accepted for publication June 10, 2020. Published online January 5, 2021.

Author contributions: Study concept and methodology: Martel, Lambertini, Agbor-Tarh, Di Cosimo, de Azambuja. Writing—original draft: Martel, Lambertini. Project administration: Martel, Lambertini. Investigation, resources, and writing—review and editing: All authors. Formal analysis: Agbor-Tarh. Supervision: Di Cosimo, de Azambuja.

Disclosures: Dr. Martel has disclosed that he has received honoraria from Novartis. Dr. Lambertini has disclosed that he has received consultant fees from Roche, Novartis, Lilly, and AstraZeneca, and received honoraria from Theramex, Roche, Lilly, Pfizer, Novartis, Sandoz, and Takeda. Dr. Ponde has disclosed that he has received honoraria from AstraZeneca, Roche, and Eli Lilly. Dr. Manukyants has disclosed that she is employed by Novartis Pharma AG. Dr. Maurer has disclosed that he has received consulting fees from Amgen, Mundipharma and SERVIER Deutschland GmbH. Dr. Piccart has disclosed that she is a board member of Oncolytics; has received honoraria from AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, Genentech, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Pfizer, Roche, and Seattle Genetics; and has received grant/research support from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche/Genentech, Servier, and Synthon. Dr. de Azambuja has disclosed that he has received grant/research support from Roche/GNE, AstraZeneca, GlaxoSmithKline/Novartis, and Servier, and consulting fees from Roche/GNE, Novartis, Seattle Genetics, Zodiac, and Libbs. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Dr. Desmedt acknowledges support from the Fondation Cancer from Luxemburg. The ALTTO trial is funded by Novartis Pharmaceuticals.

Correspondence: Samuel Martel, MD, Department of Hemato-Oncology, Hôpital Charles-Le Moyne/CISSS Montérégie-Centre, 3120 Boulevard Taschereau, Greenfield Park, Quebec, Canada. Email: samuel.martel3@usherbrooke.ca

Supplementary Materials

    • Supplemental Materials (PDF 527.13 KB)
  • 1.

    GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, .. Health Effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377:1327.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Courneya KS, Katzmarzyk PT, Bacon E. Physical activity and obesity in Canadian cancer survivors: population-based estimates from the 2005 Canadian Community Health Survey. Cancer 2008;112:24752482.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Greenlee H, Shi Z, Sardo Molmenti CL, . Trends in obesity prevalence in adults with a history of cancer: results from the US National Health Interview Survey, 1997 to 2014. J Clin Oncol 2016;34:31333140.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 2010;123:627635.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Niraula S, Ocana A, Ennis M, . Body size and breast cancer prognosis in relation to hormone receptor and menopausal status: a meta-analysis. Breast Cancer Res Treat 2012;134:769781.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Chan DSM, Vieira AR, Aune D, . Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014;25:19011914.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Cecchini RS, Swain SM, Costantino JP, . 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. Cancer Epidemiol Biomarkers Prev 2016;25:5159.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Crozier JA, Moreno-Aspitia A, Ballman KV, . Effect of body mass index on tumor characteristics and disease-free survival in patients from the HER2-positive adjuvant trastuzumab trial N9831. Cancer 2013;119:24472454.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Yerushalmi R, Dong B, Chapman JW, . Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol 2017;28:15601568.

  • 10.

    Piccart-Gebhart M, Holmes E, Baselga J, . Adjuvant lapatinib and trastuzumab for early human epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial. J Clin Oncol 2016;34:10341042.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Moreno-Aspitia A, McCormick E, Jackisch C . Updated results from the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L) or their combination (L+T) in the adjuvant treatment of HER2-positive early breast cancer [abstract]. J Clin Oncol 2017;35(Suppl):Abstract 502.

    • Search Google Scholar
    • Export Citation
  • 12.

    WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157163.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Playdon MC, Bracken MB, Sanft TB, . Weight gain after breast cancer diagnosis and all-cause mortality: systematic review and meta-analysis. J Natl Cancer Inst 2015;107:djv275.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Stevens J, Truesdale KP, McClain JE, . The definition of weight maintenance. Int J Obes 2006;30:391399.

  • 15.

    Klil-Drori AJ, Azoulay L, Pollak MN. Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing? Nat Rev Clin Oncol 2017;14:8599.

  • 16.

    Saxena NK, Taliaferro-Smith L, Knight BB, . Bidirectional crosstalk between leptin and insulin-like growth factor-I signaling promotes invasion and migration of breast cancer cells via transactivation of epidermal growth factor receptor. Cancer Res 2008;68:97129722.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Fiorio E, Mercanti A, Terrasi M, . Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis. BMC Cancer 2008;8:305.

  • 18.

    Runowicz CD, Leach CR, Henry NL, . American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol 2016;34:611635.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    The Premenopausal Breast Cancer Collaborative Group, Schoemaker MJ, Nichols HB, . Association of body mass index and age with subsequent breast cancer risk in premenopausal women. JAMA Oncol 2018;4:e181771.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Dowsett M, Folkerd E. Reduced progesterone levels explain the reduced risk of breast cancer in obese premenopausal women: a new hypothesis. Breast Cancer Res Treat 2015;149:14.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Berrington de Gonzalez A, Hartge P, Cerhan JR, . Body-mass index and mortality among 1.46 million white adults. N Engl J Med 2010;363:22112219.

  • 22.

    National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med 2000;160:898904.

  • 23.

    Finkelstein EA, Trogdon JG, Cohen JW, . Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood) 2009;28(Suppl 1):w822831.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Ligibel JA, Alfano CM, Courneya KS, . American Society of Clinical Oncology position statement on obesity and cancer. J Clin Oncol 2014;32:35683574.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Chlebowski RT, Blackburn GL, Thomson CA, . Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst 2006;98:17671776.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Chlebowski RT, Blackburn GL. Final survival analysis from the randomized Women’s Intervention Nutrition Study (WINS) evaluating dietary intervention as adjuvant breast cancer therapy. Presented at the 2014 San Antonio Breast Cancer Symposium; December 9–13, 2014; San Antonio, Texas.

  • 27.

    Chlebowski RT, Aragaki AK, Anderson GL, . Dietary modification and breast cancer mortality: long-term follow-up of the Women’s Health Initiative randomized trial. J Clin Oncol 2020;38:14191428.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Nadler M, Bainbridge D, Tomasone J, . Oncology care provider perspectives on exercise promotion in people with cancer: an examination of knowledge, practices, barriers, and facilitators. Support Care Cancer 2017;25:22972304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Griggs JJ, Mangu PB, Anderson H, . Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2012;30:15531561.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    World Health Organization. Body mass index. Accessed April 10, 2020. Available at: www.euro.who.int/en/health-topics/disease-prevention/nutrition

    • Export Citation
  • 31.

    Buss J. Limitations of body mass index to assess body fat. Workplace Health Saf 2014;62:264–264.

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 663 663 663
PDF Downloads 145 145 145
EPUB Downloads 0 0 0