Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2017
Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.
Abstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017. The graph read 3 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It also reports 3 associations that do not count as treatment evidence, such as HR 1.87 (1.23 to 2.85) for overall survival (OS). Cited by 81 papers, 4 of them syntheses that pooled it.
3numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 4 pooled it
7.2field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
Read, but not usablea number the graph found but could not read as for or against
Overall survival (OS)diabetes with no metformin treatment vs no history of diabetes at diagnosisan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 1.871.23 to 2.85P = .004
Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004).
The authors add: This effect was limited to hormone receptor-positive patients.
Distant disease-free survival (DDFS)diabetes with no metformin treatment vs no history of diabetes at diagnosisan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 1.561.10 to 2.22P = .013
Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004).
The authors add: This effect was limited to hormone receptor-positive patients.
Disease-free survival (DFS)diabetes with no metformin treatment vs no history of diabetes at diagnosisan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
HR 1.401.01 to 1.94P = .043
Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004).
The authors add: This effect was limited to hormone receptor-positive patients.
clause the extractor read what became the number
Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
Glycemic control
Body weight & composition
Lipids
Blood pressure
Cardiovascular events
All-cause mortality
Cardiac & vascular function
Kidney outcomes
Liver & MASLD
Neuropathy, eye & foot
Pregnancy & neonatal
Adverse events & safety
Hypoglycaemia
Pharmacokinetics & dosing
Inflammation & biomarkers
Quality of life & behaviour
Costs & health-care use
StatinsPCSK9 inhibitorsOther lipid agentsMetforminSGLT2 inhibitorsGLP-1 receptor agonistsGIP/GLP-1 & amylin agonistsDPP-4 inhibitorsSulfonylureas & glinidesThiazolidinedionesInsulinOther glucose-loweringAnti-obesity drugsBariatric & metabolic surgeryAntihypertensivesOther cardiovascular drugsAntiplatelet & anticoagulantCardiac procedures & devicesSupplements & botanicalsDiet, exercise & lifestyleDigital & care-deliveryInvestigational compoundssupports the treatmentfavours the comparatorno clear differenceread, but no usable result
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Metformin×all-cause mortality
No readable resultOpen on the map →What to test next →1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.
Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT000387272,779 enrolled · 1996
HR 0.990.79 to 1.25
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
81 citing papers in PubMed, 4 syntheses or guidelines pooled it, 165 citations in OpenAlex.
- Targeting Ferroptosis as the Achilles' Heel of Breast Cancer: Mechanisms and Therapeutic Opportunities from a Comprehensive Systematic Review.International journal of molecular sciences · 2025Pooled it
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Knowledge mapping of metformin use on cancers: a bibliometric analysis (2013-2023).Frontiers in pharmacology · 2024Pooled it
- Pooled it
- Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial. Preliminary Safety Analysis.Cancer prevention research (Philadelphia, Pa.) · 2026Trial
- Trial
- The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial.Scientific reports · 2022Trial
- Efficacy and safety of the combination of metformin, everolimus and exemestane in overweight and obese postmenopausal patients with metastatic, hormone receptor-positive, HER2-negative breast cancer: a phase II study.Investigational new drugs · 2019Trial
- Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.Cell metabolism · 2018Trial
- Impact of metformin-based chemo-radiotherapeutic strategies on breast cancer stemness and autophagy-associated gene expression: evidence from ALDH1A1 and LC3 expression analysis.Molecular biology reports · 2026Article
- Article
- Combination of metformin and parthenolide inhibits breast cancer in mice by apoptosis induction and angiogenesis inhibition.Frontiers in immunology · 2026Article
- Developing an interpretable machine learning model for easily detecting insulin resistance among breast cancer survivors: a cross-sectional study.BMC medical informatics and decision making · 2025Article
- Mapping the current research landscape of metformin in cancer based on bibliometric analysis.Discover oncology · 2025Article
- Metformin and weight loss medication impact on survival outcomes in older women with obesity-related cancers.Scientific reports · 2025Article
- Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis.Discover oncology · 2025Article
- Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs.Signal transduction and targeted therapy · 2025Article
- Unravelling the association between metformin and pan-cancers: Mendelian randomization combined with NHANES database analysis.Discover oncology · 2025Article
- Using routinely collected patient data to study the impact of type 2 diabetes on breast cancer.Endocrine oncology (Bristol, England) · 2025Article
- Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab.Scientific reports · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
20 authors at 9 institutions in 9 countries.
Amir SonnenblickAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Dominique Agbor-TarhAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Ian BradburyAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Serena Di CosimoAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Hatem A AzimAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Debora FumagalliAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Severine SarpAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Antonio C WolffAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Michael AnderssonAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Judith KroepAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Tanja CuferAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Sergio D SimonAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Pamela SalmanAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Masakazu ToiAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Lyndsay HarrisAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Julie GralowAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Maccon KeaneAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Alvaro Moreno-AspitiaAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Martine Piccart-GebhartAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Evandro de AzambujaAmir Sonnenblick, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Dominique Agbor-Tarh and Ian Bradbury, Frontier Science, Kingussie, United Kingdom; Serena Di Cosimo Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy; Hatem A. Azim Jr, Martine Piccart-Gebhart and Evandro de Azambuja, Université Libre de Bruxelles; Debora Fumagalli, Breast International Group, Brussels, Belgium; Severine Sarp, Novartis Pharma AG, Basel, Switzerland; Antonio C. Wolff, Johns Hopkins School of Medicine, Baltimore, MD; Lyndsay Harris, Case Western Reserve University School of Medicine, Cleveland, OH; Julie Gralow, Seattle Cancer Care Alliance, Seattle, WA; Alvaro Moreno-Aspitia, Mayo Clinic, Jacksonville, FL; Michael Andersson, Rigshospitalet University Hospital Copenhagen, Denmark; Judith Kroep, Leiden University Medical Center, Leiden, the Netherlands; Tanja Cufer, University Clinic Golnik Medical Faculty, Ljubljana, Slovenia; Sergio D. Simon, Hospital Israelita Albert Einstein; Sergio D. Simon, Grupo Brasileiro de Estudos do Cancer de Mama, São Paulo, Brazil; Pamela Salman, Fundación Arturo López Pérez, Santiago, Chile; Masakazu Toi, Kyoto University, Kyoto, Japan; Maccon Keane, University Hospital Galway, Galway; and Maccon Keane, Cancer Trials Ireland, Dublin, Ireland.
Roche (Switzerland) · CHNovartis (Ireland) · IEBristol-Myers Squibb (Germany) · DEInstitut Jules Bordet · BEMuseo De Arte Contemporaneo · PAPfizer (United Kingdom) · GBTaiho Oncology (United States) · USChugai Pharma (United States) · USPfizer (United States) · US
Funding
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3MProject-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer · 2014 to 2026
$167.6MStatistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0MTRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0MNCIC Foreign AccrualsU10CA077202 · NCI · QUEEN'S UNIVERSITY AT KINGSTON · PI EISENHAUER, ELIZABETH · 1998 to 2013
$14.6MNCI NIH HHS U10 CA025224NCI NIH HHS U10 CA077202NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882
Abstract
The marked sentences are the ones the graph read a number from.
Purpose Previous studies have suggested an association between metformin use and improved outcome in patients with diabetes and breast cancer. In the current study, we aimed to explore this association in human epidermal growth factor receptor 2 (HER2 ) -positive primary breast cancer in the context of a large, phase III adjuvant trial. Patients and Methods The ALTTO trial randomly assigned patients with HER2-positive breast cancer to receive 1 year of either trastuzumab alone, lapatinib alone, their sequence, or their combination. In this substudy, we evaluated whether patients with diabetes at study entry-with or without metformin treatment-were associated with different disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) compared with patients without diabetes. Results A total of 8,381 patients were included in the current analysis: 7,935 patients (94.7%) had no history of diabetes at diagnosis, 186 patients (2.2%) had diabetes with no metformin treatment, and 260 patients (3.1%) were diabetic and had been treated with metformin. Median follow-up was 4.5 years (0.16 to 6.31 years), at which 1,205 (14.38%), 929 (11.08%), and 528 (6.3%) patients experienced DFS, DDFS, and OS events, respectively. Patients with diabetes who had not been treated with metformin experienced worse DFS (multivariable hazard ratio [HR], 1.40; 95% CI, 1.01 to 1.94; P = .043), DDFS (multivariable HR, 1.56; 95% CI, 1.10 to 2.22; P = .013), and OS (multivariable HR, 1.87; 95% CI, 1.23 to 2.85; P = .004). This effect was limited to hormone receptor-positive patients. Whereas insulin treatment was associated with a detrimental effect, metformin had a salutary effect in patients with diabetes who had HER2-positive and hormone receptor-positive breast cancer. Conclusion Metformin may improve the worse prognosis that is associated with diabetes and insulin treatment, mainly in patients with primary HER2-positive and hormone receptor-positive breast cancer.
Indexed as
Antineoplastic AgentsBreast NeoplasmsDiabetes MellitusDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesFemaleHumansHypoglycemic AgentsInsulinLapatinibMetforminMiddle AgedQuinazolinesTrastuzumabAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHypoglycemic AgentsInsulinLapatinibMetforminQuinazolinesTrastuzumab
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.