dc.contributor.author | Goodwin, PJ | |
dc.contributor.author | Chen, BE | |
dc.contributor.author | Gelmon, KA | |
dc.contributor.author | Whelan, TJ | |
dc.contributor.author | Ennis, M | |
dc.contributor.author | Lemieux, J | |
dc.contributor.author | Ligibel, JA | |
dc.contributor.author | Hershman, DL | |
dc.contributor.author | Mayer, IA | |
dc.contributor.author | Hobday, TJ | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Rastogi, P | |
dc.contributor.author | Rabaglio-Poretti, M | |
dc.contributor.author | Mukherjee, SD | |
dc.contributor.author | Mackey, JR | |
dc.contributor.author | Abramson, VG | |
dc.contributor.author | Oja, C | |
dc.contributor.author | Wesolowski, R | |
dc.contributor.author | Thompson, AM | |
dc.contributor.author | Rea, DW | |
dc.contributor.author | Stos, PM | |
dc.contributor.author | Shepherd, LE | |
dc.contributor.author | Stambolic, V | |
dc.contributor.author | Parulekar, WR | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-11-25T09:33:10Z | |
dc.date.available | 2022-11-25T09:33:10Z | |
dc.date.issued | 2022-05-24 | |
dc.identifier | 2792615 | |
dc.identifier.citation | JAMA: Journal of the American Medical Association, 2022, 327 (20), pp. 1963 - 1973 | |
dc.identifier.issn | 0098-7484 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5574 | |
dc.identifier.eissn | 1538-3598 | |
dc.identifier.eissn | 1538-3598 | |
dc.identifier.doi | 10.1001/jama.2022.6147 | |
dc.description.abstract | IMPORTANCE: Metformin, a biguanide commonly used to treat type 2 diabetes, has been associated with potential beneficial effects across breast cancer subtypes in observational and preclinical studies. OBJECTIVE: To determine whether the administration of adjuvant metformin (vs placebo) to patients with breast cancer without diabetes improves outcomes. DESIGN, SETTING, AND PARTICIPANTS: MA.32, a phase 3 randomized, placebo-controlled, double-blind trial, conducted in Canada, Switzerland, US, and UK, enrolled 3649 patients with high-risk nonmetastatic breast cancer receiving standard therapy between August 2010 and March 2013, with follow-up to October 2020. INTERVENTIONS: Patients were randomized (stratified for hormone receptor [estrogen receptor and/or progesterone receptor {ER/PgR}] status, positive vs negative; body mass index, ≤30 vs >30; human epidermal growth factor receptor 2 [ERBB2, formerly HER2 or HER2/neu], positive vs negative; and any vs no chemotherapy) to 850 mg of oral metformin twice a day (n = 1824) or oral placebo twice a day (n = 1825) for 5 years. MAIN OUTCOMES AND MEASURES: The primary outcome was invasive disease-free survival in hormone receptor-positive breast cancer. Of the 8 secondary outcomes, overall survival, distant relapse-free survival, and breast cancer-free interval were analyzed. RESULTS: Of the 3649 randomized patients (mean age, 52.4 years; 3643 women [99.8%]), all (100%) were included in analyses. After a second interim analysis, futility was declared for patients who were ER/PgR-, so the primary analysis was conducted for 2533 patients who were ER/PgR+. The median duration of follow-up in the ER/PgR+ group was 96.2 months (range, 0.2-121 months). Invasive disease-free survival events occurred in 465 patients who were ER/PgR+. The incidence rates for invasive disease-free survival events were 2.78 per 100 patient-years in the metformin group vs 2.74 per 100 patient-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.84-1.21; P = .93), and the incidence rates for death were 1.46 per 100 patient-years in the metformin group vs 1.32 per 100 patient-years in the placebo group (HR, 1.10; 95% CI, 0.86-1.41; P = .47). Among patients who were ER/PgR-, followed up for a median of 94.1 months, incidence of invasive disease-free survival events was 3.58 vs 3.60 per 100 patient-years, respectively (HR, 1.01; 95% CI, 0.79-1.30; P = .92). None of the 3 secondary outcomes analyzed in the ER/PgR+ group had statistically significant differences. Grade 3 nonhematological toxic events occurred more frequently in patients taking metformin than in patients taking placebo (21.5% vs 17.5%, respectively, P = .003). The most common grade 3 or higher adverse events in the metformin vs placebo groups were hypertension (2.4% vs 1.9%), irregular menses (1.5% vs 1.4%), and diarrhea (1.9% vs 7.0%). CONCLUSIONS AND RELEVANCE: Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01101438. | |
dc.format | Print | |
dc.format.extent | 1963 - 1973 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER MEDICAL ASSOC | |
dc.relation.ispartof | JAMA: Journal of the American Medical Association | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Administration, Oral | |
dc.subject | Antineoplastic Agents | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Breast Neoplasms | |
dc.subject | Disease-Free Survival | |
dc.subject | Double-Blind Method | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Metformin | |
dc.subject | Middle Aged | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Receptor, ErbB-2 | |
dc.subject | Receptors, Estrogen | |
dc.subject | Receptors, Progesterone | |
dc.title | Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-05-24 | |
dc.date.updated | 2022-11-24T14:54:21Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1001/jama.2022.6147 | |
rioxxterms.licenseref.startdate | 2022-05-24 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/35608580 | |
pubs.issue | 20 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1001/jama.2022.6147 | |
pubs.volume | 327 | |
icr.researchteam | Clin Trials & Stats Unit | |
dc.contributor.icrauthor | Bliss, Judith | |
icr.provenance | Deposited by Mrs Jessica Perry (impersonating Prof Judith Bliss) on 2022-11-24. Deposit type is initial. No. of files: 1. Files: jama_goodwin_2022_oi_220046_1652813403.66253.pdf | |