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

Authors:
Samuel Martel Department of Hemato-Oncology, CISSS Montérégie Centre/Hôpital Charles Le Moyne, Université de Sherbrooke, Greenfield Park, Quebec, Canada;

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Matteo Lambertini Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy;

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Dominique Agbor-Tarh Frontier Science, Kingussie, United Kingdom;

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Noam F. Ponde Department of Medicine, Camargo Cancer Center, Sao Paulo, Brazil;

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Andrea Gombos Institut Jules Bordet and L’Université Libre de Bruxelles (U.L.B.), Brussels, Belgium;

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Vicki Paterson Frontier Science, Kingussie, United Kingdom;

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Florentine Hilbers Breast International Group, Brussels, Belgium;

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Larissa Korde National Cancer Institute, Bethesda, Maryland;

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Anna Manukyants Novartis Pharma AG, Basel, Switzerland;

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Amylou Dueck Mayo Clinic, Jacksonville, Florida;

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Christian Maurer University of Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany;

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Martine Piccart Institut Jules Bordet and L’Université Libre de Bruxelles (U.L.B.), Brussels, Belgium;

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Alvaro Moreno-Aspitia Mayo Clinic, Jacksonville, Florida;

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Christine Desmedt Laboratory for Translational Breast Cancer Research, Department of Oncology, Leuven, Belgium; and

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Serena Di Cosimo Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

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Evandro de Azambuja Institut Jules Bordet and L’Université Libre de Bruxelles (U.L.B.), Brussels, Belgium;

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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

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