ArticleNPJ breast cancer2021
Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.
Open access · goldAbstract read
In one paragraph
Article in NPJ breast cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta-analysis of randomized trials.Cancer medicine · 2024Pooled it
- Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti-Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Trial
- Ki67 Gene Expression is Associated with Immune Cell Infiltration and Neoadjuvant Chemotherapy Response in ER+/HER2- Breast Cancer.Annals of surgical oncology · 2026Article
- Recent advances in targeted therapies and immunotherapies for triple-negative breast cancer.Frontiers in oncology · 2026Review
- Reduced IGF-1 signaling fails to limit Alzheimer's disease progression in a novel rat model of IGF-1R haploinsufficiency.Scientific reports · 2025Article
- Translating Metabolic Interventions into Breast Cancer Therapy: A Comprehensive Review.Life (Basel, Switzerland) · 2025Review
- The clinical potentials of combining paclitaxel-based chemotherapy regimen with metformin in cancer treatment: A systematic review and Meta-analysis.Translational oncology · 2025Review
- Immune Subtyping Identifies Patients With Hormone Receptor-Positive Early-Stage Breast Cancer Who Respond to Neoadjuvant Immunotherapy (IO): Results From Five IO Arms of the I-SPY2 Trial.JCO precision oncology · 2025Article
- Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort.Carcinogenesis · 2025Article
- Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression.NPJ precision oncology · 2024Article
- Cancer biology in diabetes update: Focusing on antidiabetic drugs.Journal of diabetes investigation · 2024Review
- Oncolytic Adenovirus for the Targeting of Paclitaxel-Resistant Breast Cancer Stem Cells.Viruses · 2024Article
- Article
- Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.JAMA network open · 2023Article
- Insulin-like growth factor-1 receptor crosstalk with integrins, cadherins, and the tumor microenvironment: sticking points in understanding IGF1R function in cancer.Endocrine-related cancer · 2023Review
- Metformin promotes cGAS/STING signaling pathway activation by blocking AKT phosphorylation in gastric cancer.Heliyon · 2023Article
- Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?British journal of cancer · 2023Review
- Tumour, whole-blood, plasma and tissue concentrations of metformin in lung cancer patients.British journal of clinical pharmacology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors at 20 institutions in 1 country.
Douglas YeeMasonic Cancer Center, University of Minnesota, 420 Delaware St., SE, MMC 480, Minneapolis, MN, 55455, USA. yeexx006@umn.edu.ORCID http://orcid.org/0000-0002-3387-4009
Claudine IsaacsGeorgetown University, 3800 Reservoir Rd, NW, Washington, DC, 20007, USA.ORCID http://orcid.org/0000-0002-9646-1260
Denise M WolfUniversity of California San Francisco Department of Laboratory Medicine, 2340 Sutter Street, S433, San Francisco, CA, 94115, USA.
Christina YauUniversity of California San Francisco Department of Laboratory Medicine, 2340 Sutter Street, S433, San Francisco, CA, 94115, USA.
Paul HaluskaMayo Clinic Rochester c/o Merck Corporation, 126 E. Lincoln Ave Rahway, New Jersey, 07065, USA.
Karthik V GiridharMayo Clinic Division of Medical Oncology, 200 1st St SW, Rochester, MN, 55905, USA.ORCID http://orcid.org/0000-0003-4640-9197
Andres Forero-TorresUniversity of Alabama at Birmingham c/o Seattle Genetics, 21823 30th Drive S.E., Bothell, WA, 98021, USA.
A Jo ChienUniversity of California San Francisco Division of Hematology-Oncology, 550 16th Street, San Francisco, CA, 94158, USA.
Anne M WallaceUniversity of California San Diego Department of Surgery, 3855 Health Sciences Dr, M/C 0698, La Jolla, CA, 92093, USA.
Lajos PusztaiYale University Medical Onciology, 111 Goose Lane, Fl 2, Guilford, CT, 06437, USA.ORCID http://orcid.org/0000-0001-9632-6686
Kathy S AlbainLoyola University Chicago Stritch School of Medicine Cardinal Bernardin Cancer Center, 2160 South First Ave, Maywood, IL, 60153, USA.
Erin D EllisSwedish Cancer Institute Medical Oncology, 1221 Madison Street, Seattle, WA, 98104, USA.
Heather BeckwithMasonic Cancer Center, University of Minnesota, 420 Delaware St., SE, MMC 480, Minneapolis, MN, 55455, USA.
Barbara B HaleyUT Southwestern Medical Center Division of Hematology-Oncology, 5323 Harry Hines Blvd, Bldg E6.222D, Dallas, TX, 75390-9155, USA.
Anthony D EliasUniversity of Colorado Anschutz Medical Center Division of Medical Oncology, 1665 Aurora Ct., Rm. 3200, MS F700, Aurora, CO, 80045, USA.
Judy C BougheyMayo Clinic Division of Medical Oncology, 200 1st St SW, Rochester, MN, 55905, USA.
Kathleen KemmerOHSU Knight Cancer Institute South Waterfront Center for Health and Healing, 3303 SW Bond Ave Building 1, Suite 7, Portland, OR, 97239, USA.
Rachel L YungUniversity of Washington Seattle Cancer Care Alliance, 825 Eastlake Ave East, Seattle, WA, 98109-1023, USA.
Paula R PohlmannGeorgetown University, 3800 Reservoir Rd, NW, Washington, DC, 20007, USA.ORCID http://orcid.org/0000-0001-7914-5162
Debu TripathyMD Anderson Cancer Center, 1515 Holcombe, Houston, Texas, 77030, USA.ORCID http://orcid.org/0000-0002-5711-2404
Amy S ClarkUniversity of Pennsylvania Division of Hematology-Oncology 3 Perelman Center, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-3685-6535
Hyo S HanMoffit Cancer Center, 2902 USF Magnolia Drive, Tampa, FL, 33612, USA.
Rita NandaUniversity of Chicago Section of Hematology/Oncology, 5841S. Maryland Avenue, MC 2115, Chicago, IL, 60437, USA.ORCID http://orcid.org/0000-0001-5248-0876
Qamar J KhanUniversity of Kansas Division of Oncology, 2330 Shawnee Mission Pkwy, Ste 210, Westwood, KS, 66205, USA.ORCID http://orcid.org/0000-0002-6287-020X
Kristen K EdmistonInova Medical Group, 3580 Joseph Siewick Dr 101, Fairfax, VA, 22033-1764, USA.
Emanuel F PetricoinGeorge Mason University Institute for Advanced Biomedical Research, 10920 George Mason Circle Room 2008, MS1A9, Manassas, Virginia, 20110, USA.
Erica Stringer-ReasorUniversity of Alabama at Birmingham Hematology/Oncology, 1802 Sixth Avenue South 2510, Birmingham, AL, 35294-3300, USA.
Carla I FalksonWilmot Cancer Institute Pluta Cancer Center, 125 Red Creek Drive, Rochester, NY, 14623, USA.
Melanie MajureUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Rita A MukhtarUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Teresa L HelstenUniversity of California San Diego Division of Hematology-Oncology, 9400 Campus Point Dr, La Jolla, CA, 92037, USA.
Stacy L MoulderMD Anderson Cancer Center, 1515 Holcombe, Houston, Texas, 77030, USA.
Patricia A RobinsonLoyola University Chicago Stritch School of Medicine Cardinal Bernardin Cancer Center, 2160 South First Ave, Maywood, IL, 60153, USA.
Julia D WulfkuhleGeorge Mason University Institute for Advanced Biomedical Research, 10920 George Mason Circle Room 2008, MS1A9, Manassas, Virginia, 20110, USA.
Lamorna Brown-SwigartUniversity of California San Francisco Department of Laboratory Medicine, 2340 Sutter Street, S433, San Francisco, CA, 94115, USA.ORCID http://orcid.org/0000-0003-2076-5177
Meredith BuxtonUniversity of California San Francisco c/o Global Coalition for Adaptive Research, 1661 Massachusetts Ave, Lexington, MA, 02420, USA.
Julia L ClennellUniversity of California San Francisco c/o IQVIA, 135 Main St 21 floor, San Francisco, CA, 94105, USA.
Melissa PaoloniPoint Eden Way, Hayward, CA, 94545, USA.
Ashish SanilBerry Consultants, LLC 3345 Bee Cave Rd Suite 201, Austin, TX, 78746, USA.
Scott BerryBerry Consultants, LLC 3345 Bee Cave Rd Suite 201, Austin, TX, 78746, USA.
Smita M AsareQuantum Leap Healthcare Collaborative, 3450 California St, San Francisco, CA, 94143, USA.
Amy WilsonQuantum Leap Healthcare Collaborative, 3450 California St, San Francisco, CA, 94143, USA.
Gillian L HirstUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-4502-0035
Ruby SinghraoUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Adam L AsareQuantum Leap Healthcare Collaborative, 3450 California St, San Francisco, CA, 94143, USA.
Jeffrey B MatthewsUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Nola M HyltonUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-6747-1662
Angela DeMicheleUniversity of Pennsylvania Division of Hematology-Oncology 3 Perelman Center, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0003-1297-4251
Michelle MeliskoUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Jane PerlmutterUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
Hope S RugoUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.
W Fraser SymmansMD Anderson Cancer Center, 1515 Holcombe, Houston, Texas, 77030, USA.ORCID http://orcid.org/0000-0002-1526-184X
Laura J Van't VeerUniversity of California San Francisco Department of Laboratory Medicine, 2340 Sutter Street, S433, San Francisco, CA, 94115, USA.ORCID http://orcid.org/0000-0002-9838-8298
Donald A BerryQuantum Leap Healthcare Collaborative, 3450 California St, San Francisco, CA, 94143, USA.
Laura J EssermanUniversity of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0001-9202-4568
University of California, San Francisco · USQuantum Leap Healthcare Collaborative · USThe University of Texas MD Anderson Cancer Center · USBerry & Associates (United States) · USGeorge Mason University · USGeorgetown University · USLoyola University Chicago · USMayo Clinic in Arizona · USUniversity of Alabama at Birmingham · USUniversity of California San Diego · USUniversity of Minnesota · USUniversity of Pennsylvania · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USMoffitt Cancer Center · USNova Medical (United States) · USOHSU Knight Cancer InstituteSeattle Cancer Care Alliance · USSouthwestern Medical CenterSwedish Medical Center · USUniversity of Chicago · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MThe I SPY 2.2 TRIAL: Evolving to Imaging and Molecular Biomarker Response Directed Adaptive Sequential Treatment to Optimize Breast Cancer OutcomesP01CA210961 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nola M. Hylton-Watson · 2017 to 2026
$22.9MQuantitative Imaging for Assessing Breast Cancer Response to TreatmentU01CA225427 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HYLTON-WATSON, NOLA M. · 2018 to 2022
$3.2MNCATS NIH HHS UL1 TR001863NCI NIH HHS P01 CA210961NCI NIH HHS U01 CA225427
Abstract
I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.
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