The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer
Open accessAbstract
Purpose: Population studies have suggested that metformin use in diabetic patients decreases cancer incidence and mortality. Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there is little clinical data to support this. Our purpose was to determine whether metformin use was associated with a change in pathologic complete response (pCR) rates in diabetic patients with breast cancer receiving neoadjuvant chemotherapy. Patients and Methods: We identified 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. Patients were compared by groups: 68 diabetic patients taking metformin, 87 diabetic patients not taking metformin, and 2,374 nondiabetic patients. pCR rates were compared between the three groups using χ 2 tests of independence and compared pair- wise using a binomial test of proportions. Factors predictive of pCR were assessed using a multivariate logistic regression model. Results: The rate of pCR was 24% in the metformin group, 8.0% in the nonmetformin group, and 16% in the nondiabetic group (P = .02). Pairwise comparisons between the metformin and nonmetformin groups (P = .007) and the nonmetformin and nondiabetic groups (P = .04) were significant. Comparison of the pCR rates between the metformin and nondiabetic groups trended toward but did not meet significance (P = .10). Metformin use was independently predictive of pCR (odds ratio, 2.95; P = .04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use. Conclusion: Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Metformin has also been found to cooperate with neo-adjuvant chemotherapy to result in complete tumor regression in some breast cancer patients (Jiralerspong et al., 2009).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Jiralerspong et al., 2009
In the citing paper
“Type 2 diabetic patients receiving neo-adjuvant chemotherapy for breast cancer as well as metformin were more likely to have pathologic complete response (pCR) than patients not receiving it.”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [156]
In the citing paper
“However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate [156].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [156]
In the citing paper
“evidence that metformin may also have an adjunctive effect in patients receiving chemotherapy(270)”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [270]
In the citing paper
“There is further evidence that metformin may also have an adjunctive effect in patients receiving chemotherapy(270), and there are now more than 100 ongoing trials”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [270]
In the citing paper
“Metformin treatment was associated with higher pathologic complete response among early-stage breast cancer patients receiving neoadjuvant therapy (95).”
From Diabetes and Cancer (2010) · cites this paper as [95]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults
Calle, E. E., Rodriguez, C., Walker-Thurmond, K., & Thun, M. J. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021423 · Cited by 7,696
Renehan, A. G., Tyson, M., Egger, M., Heller, R. F., & Zwahlen, M. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60269-x · Cited by 5,219
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms
Calle, E. E., & Kaaks, R. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1408 · Cited by 3,613
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
Rastogi, P., Anderson, S. J., Bear, H. D., Geyer, C. E., Kahlenberg, M. S., Robidoux, A., Margolese, R. G., Hoehn, J. L., Vogel, V. G., Dakhil, S. R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.0235 · Cited by 1,789
Insulin-like growth factors and neoplasia
Pollak, M., Schernhammer, E. S., & Hankinson, S. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1387 · Cited by 1,477
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Muoio, D. M., & Newgard, C. B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2327 · Cited by 1,177
The LKB1 tumor suppressor negatively regulates mTOR signaling
Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,107
Research works printed but not linked: 3
- Mieog JS, 2007, Cochrane Database Syst Rev, 2, CD005002
- 10.1200/JCO.2002.20.1.42 · DOI
- Fairey AS, 2003, Cancer Epidemiol Biomarkers Prev, 12, 721
Cited by
Sorted by citations
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366
“Metformin treatment was associated with higher pathologic complete response among early-stage breast cancer patients receiving neoadjuvant therapy (95).”
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression
Shackelford, D. B., & Shaw, R. J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2676 · Cited by 1,943
“Similarly, a recent study of breast cancer in patients with type 2 diabetes who were taking metformin reported a significant increase in pathological complete response rates (that is, no evidence of cancer cells in breast tissue or draining lymph nodes”
BackgroundTargeting cancer metabolism: a therapeutic window opens
Heiden, M. G. V. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3504 · Cited by 1,443
“, and women taking metformin have an increased tumour response to neoadjuvant chemotherapy for breast cancer that may extend to patients with cancer who do not have diabete”
BackgroundThe Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
Levine, A. J., & Puzio-Kuter, A. M. (2010) · Science · doi:10.1126/science.1193494 · Cited by 1,243
Hirsch, H. A., Iliopoulos, D., Tsichlis, P. N., & Struhl, K. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-2994 · Cited by 1,115
“epidemiologic observation that diabetics treated with metformin have a lower incidence of cancer (5, 6).”
BackgroundTargeting metabolic transformation for cancer therapy
Tennant, D. A., Durán, R. V., & Gottlieb, E. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2817 · Cited by 1,073
“A further study on diabetic patients with breast cancer as well as studies on breast cancer cells in vitro and a mouse model of breast cancer also found an anti-tumour effect of metformi”
BackgroundDiabetes and Cancer: A Consensus Report
Giovannucci, E. L., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20078 · Cited by 1,082
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
“Metformin has also been found to cooperate with neo-adjuvant chemotherapy to result in complete tumor regression in some breast cancer patients (Jiralerspong et al., 2009).”
BackgroundRapamycin passes the torch: a new generation of mTOR inhibitors
Benjamin, D., Colombi, M., Moroni, C., & Hall, M. N. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3531 · Cited by 1,013
Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer
Du, B., & Shim, J. S. (2016) · Molecules · doi:10.3390/molecules21070965 · Cited by 829
Triple-negative breast cancer: disease entity or title of convenience?
Carey, L., Winer, E. P., Viale, G., Cameron, D., & Gianni, L. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.154 · Cited by 791
“There is also evidence that metformin may enhance the efficacy of chemotherapy in patients with breast cancer (of unspecified molecular subtype”
BackgroundMetformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis
DeCensi, A., Puntoni, M., Goodwin, P., Cazzaniga, M., Gennari, A., Bonanni, B., & Gandini, S. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0157 · Cited by 918
Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways
Eroles, P., Bosch, A., Fidalgo, J. A. P., & Lluch, A. M. (2011) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2011.11.005 · Cited by 678
“Furthermore, a retrospective study linked metformin use with a higher probability of pCR in the neoadjuvant setting.(77) Taking all of this together, the use of metformin in breast cancer treatment looks very promising and several clinical trials are exploring the usefulness of this drug in advanced and early breast c…”
BackgroundMetformin: An Old But Still the Best Treatment for Type 2 Diabetes
Rojas, L. B. A., & Gomes, M. B. (2013) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-5-6 · Cited by 567
“However, despite the increase in pCR, metformin did not significantly improve the estimated 3-year relapse-free survival rate [156].”
BackgroundCancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis
Noto, H., Goto, A., Tsujimoto, T., & Noda, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033411 · Cited by 566
“The fact that one preliminary study suggested a promising effect of metformin on pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer [87] may point to the possibility that metformin simply augmented the efficacy of chemotherapy for breast cancer [18,86].”
BackgroundPI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis
Schultze, S. M., Hemmings, B. A., Nießen, M., & Tschopp, O. (2012) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002109 · Cited by 553
Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning
Pollak, M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0263 · Cited by 512
Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes
Landman, G. W. D., Kleefstra, N., van Hateren, K. J. J., Groenier, K. H., Gans, R. O. B., & Bilo, H. J. G. (2010) · Diabetes Care · doi:10.2337/dc09-1380 · Cited by 502
“For example, type 2 diabetic patients receiving neoadjuvant chemotherapy for breast cancer as well as metformin were more likely to have a complete remission than patients not receiving metformin (14).”
Metformin in cancer therapy: a new perspective for an old antidiabetic drug?
Ben Sahra, I., Le Marchand-Brustel, Y., Tanti, J.-F., & Bost, F. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-1186 · Cited by 493
“combination of metformin and chemotherapy (67)”
Metformin in Cancer Treatment and Prevention
Morales, D. R., & Morris, A. D. (2014) · Annual Review of Medicine · doi:10.1146/annurev-med-062613-093128 · Cited by 494
Melhem‐Bertrandt, A., Chávez‐MacGregor, M., Lei, X. J., Brown, E. N., Lee, R. T., Meric‐Bernstam, F., Sood, A. K., Conzen, S. D., Hortobágyi, G. N., & Gonzalez-Angulo, A. M. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.4441 · Cited by 471
Self-citationLong-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer
Bodmer, M., Meier, C., Krähenbühl, S., Jick, S. S., & Meier, C. R. (2010) · Diabetes Care · doi:10.2337/dc09-1791 · Cited by 466
“Female diabetic patients receiving neoadjuvant chemotherapy for breast cancer were reported to have a higher complete pathologic response rate if they also used metformin compared with those not using metformin (10).”
BackgroundIliopoulos, D., Hirsch, H. A., & Struhl, K. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3471 · Cited by 459
“org Cancer Res; 71(9) May 1, 2011 3199”
BackgroundInfluentialDiabetes Mellitus and Breast Cancer Outcomes: A Systematic Review and Meta-Analysis
Peairs, K. S., Barone, B. B., Snyder, C. F., Yeh, H., Stein, K. B., Derr, R. L., Brancati, F. L., & Wolff, A. C. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.3011 · Cited by 451
Hirsch, H. A., Iliopoulos, D., & Struhl, K. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221055110 · Cited by 440
“Biochem Biophys Res Commun 425(4): 866–872.”
BackgroundInfluentialMetformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review
Franciosi, M., Lucisano, G., Lapice, E., Strippoli, G. F. M., Pellegrini, F., & Nicolucci, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071583 · Cited by 428
“lung cancer treated with metformin [82,83].”
Understanding the benefit of metformin use in cancer treatment
Dowling, R. J. O., Goodwin, P. J., & Stambolic, V. (2011) · BMC Medicine · doi:10.1186/1741-7015-9-33 · Cited by 417
“Furthermore, a recent epidemiological study of 2,529 women with breast cancer reported higher pathologic complete response rates (pCRs; considered a surrogate for overall survival in this setting) to neoadjuvant systemic therapy in diabetic patients receiving metformin (pCR 24%) compared to diabetic patients not recei…”
BackgroundObesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities
Jiralerspong, S., & Goodwin, P. J. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.68.4480 · Cited by 415
Self-citationChen, H.-P., Shieh, J., Chang, C., Chen, T.-T., Lin, J., Wu, M., Lin, J.-H., & Wu, C. (2012) · Gut · doi:10.1136/gutjnl-2011-301708 · Cited by 399
AMPK As a Metabolic Tumor Suppressor: Control of Metabolism and Cell Growth
Luo, Z., Zang, M., & Guo, W. (2010) · Future Oncology · doi:10.2217/fon.09.174 · Cited by 392
“Interestingly, one clinical study assessed the response of breast cancer patients with diabetes to nonadjuvant chemotherapy in combination with metformin or with nonmetformin anti diabetic drugs and demonstrated that the patients receiving metformin showed complete pathological responses [119].”
BackgroundThe proliferating role of insulin and insulin-like growth factors in cancer
Gallagher, E. J., & LeRoith, D. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.06.007 · Cited by 398
“In human epidemiological studies, metformin has been associated with a decreased risk of cancer development and a better response to chemotherapy in patients with breast cancer [70,71].”
BackgroundMetformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer
Yang, J., Zhou, Y., Xie, S., Wang, J., Li, Z., Chen, L., Mao, M., Chen, C., Huang, A., Chen, Y., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02012-7 · Cited by 399
Metformin: Taking away the candy for cancer?
Jalving, M., Gietema, J. A., Lefrandt, J. D., de Jong, S., Reyners, A. K. L., Gans, R. O. B., & de Vries, E. G. E. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.06.012 · Cited by 382
Inflammatory Breast Cancer: The Disease, the Biology, the Treatment
Robertson, F. M., Bondy, M. L., Yang, W. T., Yamauchi, H., Wiggins, S., Kamrudin, S. A., Krishnamurthy, S., Le‐Petross, H. T., Bidaut, L. M., Player, A. N., et al. (2010) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20082 · Cited by 369
Targeting Breast Cancer Stem Cells
Liu, S., & Wicha, M. S. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.5388 · Cited by 365
Metformin in cancer: translational challenges
Dowling, R. J. O., Niraula, S., Stambolic, V., & Goodwin, P. J. (2012) · Journal of Molecular Endocrinology · doi:10.1530/jme-12-0007 · Cited by 371
“Jiralerspong et al. (2009) studied pathological complete response (pCR) rates in breast cancer patients receiving neoadjuvant chemotherapy – pCR was significantly higher in diabetics receiving metformin than in diabetics not receiving metformin (24 vs 8%), with intermediate pCR in non-diabetics who…”
BackgroundSaraei, P., Asadi, I., Kakar, M. A., & Moradikor, N. (2019) · Cancer Management and Research · doi:10.2147/cmar.s200059 · Cited by 361
“Furthermore, according to the results of research by Jiralespnog et al on diabetic (n=155) and non-diabetic (n=2,374) patients with breast cancer, pathologic complete remission (pCR) of patients taking metformin along with chemotherapy was higher compared to patients who did not receive metformin.(99) Other related st…”
ResultMetformin in cancer prevention and therapy.
Kasznicki, J., Śliwińska, A., & Drzewoski, J. (2014) · PubMed Central · doi:10.3978/j.issn.2305-5839.2014.06.01 · Cited by 362
“They noted increased incidence of complete response rates in metformin group, both in patients with and without diabetes (58).”
BackgroundParacrine and Endocrine Effects of Adipose Tissue on Cancer Development and Progression
Park, J., Euhus, D., & Scherer, P. E. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0030 · Cited by 361
Gui, D. Y., Sullivan, L. B., Luengo, A., Hosios, A. M., Bush, L. N., Gitego, N., Davidson, S. M., Freinkman, E., Thomas, C. J., & Vander Heiden, M. G. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.006 · Cited by 323
“Metformin may also increase the pathological complete response rate in breast cancer patients receiving neoadjuvant chemotherapy (Jiralerspong et al., 2009).”
Cancer drug discovery by repurposing: teaching new tricks to old dogs
Gupta, S. C., Sung, B., Prasad, S., Webb, L. J., & Aggarwal, B. B. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.06.005 · Cited by 355
Metformin: a review of its potential indications
Wang, Y., He, S., Feng, X., Cheng, J. Q., Luo, Y.-T., Tian, L., & Huang, Q. (2017) · Drug Design Development and Therapy · doi:10.2147/dddt.s141675 · Cited by 330
Shi, W.-Y., Xiao, D., Wang, L., Dong, L.-H., Yan, Z.-X., Shen, Z.-X., Chen, S.-J., Chen, Y., & Zhao, W.-L. (2012) · Cell Death & Disease · doi:10.1038/cddis.2012.13 · Cited by 308
“Clinically, retrospective analyses suggested that metformin may improve patient response following neo-adjuvant chemotherapy for breast cancer.(20)”
BackgroundMetformin Amplifies Chemotherapy-Induced AMPK Activation and Antitumoral Growth
Rocha, G. Z., Dias, M. M., Ropelle, E. R., Osório–Costa, F., Rossato, F. A., Vercesi, A. E., Saad, M. J. A., & Carvalheira, J. B. C. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2243 · Cited by 315
Metformin Use Is Associated with Better Survival of Diabetic Patients with Pancreatic Cancer
Sadeghi, N., Abbruzzese, J. L., Yeung, S. J., Hassan, M. M., & Li, D. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2994 · Cited by 308
Metformin: Multi-faceted protection against cancer
Barco, S. D., Vázquez‐Martín, A., Cufí, S., Oliveras‐Ferraros, C., Bosch‐Barrera, J., Joven, J., Martı́n-Castillo, B., & Menéndez, J. A. (2011) · Oncotarget · doi:10.18632/oncotarget.387 · Cited by 307
“Because of this, it is tempting to suggest that, in the context of DDR, metformin-enhanced cellular senescence may underlie metformin’s ability to increase the rate of pCR in neoadjuvant chemotherapy in diabetic patients with breast cancer [33] and to promote tumor regression and prevent relapse when combined with sub…”
BackgroundResultObesity, type 2 diabetes, and cancer: the insulin and IGF connection
Cohen, D., & LeRoith, D. (2012) · Endocrine Related Cancer · doi:10.1530/erc-11-0374 · Cited by 308
“Jiralerspong et al .”
InfluentialDonadon, V., Balbi, M., Mas, M. D., Casarin, P., & Zanette, G. (2010) · Liver International · doi:10.1111/j.1478-3231.2010.02223.x · Cited by 292
“Obesity is associated with excess cancer mortality (12), mediated, at least in part, by overweightrelated hyperinsulinaemia, and the potential clinical and public health relevance of this problem is now under intense investigation (56, 57).”
BackgroundHadad, S. M., Iwamoto, T., Jordan, L. B., Purdie, C. A., Bray, S. E., Baker, L., Jellema, G. L., Deharo, S., Hardie, D. G., Pusztai, L., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1612-1 · Cited by 293
“Coincidental use of metformin in diabetics undergoing neoadjuvant chemotherapy for breast cancer resulted in a higher pathological complete response (24%), compared with diabetics not on metformin (8%) or non-diabetic patients (16%) [3].”
ResultThe fat side of prostate cancer
Zadra, G., Photopoulos, C., & Loda, M. F. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.03.010 · Cited by 301
Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer
Duggan, C. R., Irwin, M. L., Xiao, L., Henderson, K. D., Smith, A. W., Baumgartner, R., Baumgartner, K. B., Bernstein, L., Ballard-Barbash, R. R., & McTiernan, A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.4473 · Cited by 291
“04).(57) This has prompted clinical trials of metformin, including a trial of neoadjuvant chemotherapy and trastuzumab with or without metformin in women diagnosed with HER2-positive primary breast cancer.”
BackgroundSkinner, H. D., Sandulache, V. C., Ow, T. J., Meyn, R. E., Yordy, J. S., Beadle, B. M., Fitzgerald, A. L., Giri, U. P., Ang, K. K., & Myers, J. N. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2260 · Cited by 291
“Recently, it has been shown that patients taking metformin have improved responses following neoadjuvant chemotherapy (49) and that metformin is a radiosensitizer in vitro (50).”
Metformin and cancer: new applications for an old drug
Kourelis, T., & Siegel, R. D. (2011) · Medical Oncology · doi:10.1007/s12032-011-9846-7 · Cited by 294
“identified approximately 155 diabetic and 2,374 nondiabetic patients with breast cancer and showed that diabetic patients receiving metformin and neoadjuvant taxane chemotherapy have a higher pathologic complete remission (pCR) rate than do diabetics not receiving metformin [84].”
BackgroundRepositioning metformin for cancer prevention and treatment
Quinn, B. J., Kitagawa, H., Memmott, R. M., Gills, J. J., & Dennis, P. A. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.05.004 · Cited by 290
Caveolin-1 and Cancer Metabolism in the Tumor Microenvironment: Markers, Models, and Mechanisms
Sotgia, F., Martinez‐Outschoorn, U., Howell, A., Pestell, R. G., Pavlides, S., & Lisanti, M. P. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-120856 · Cited by 290
Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells
Song, C. W., Lee, H., Dings, R. P. M., Williams, B. W., Powers, J., Santos, T. D., Choi, B., & Park, H. J. (2012) · Scientific Reports · doi:10.1038/srep00362 · Cited by 284
Wright, J. L., & Stanford, J. L. (2009) · Cancer Causes & Control · doi:10.1007/s10552-009-9407-y · Cited by 276
Diabetes and cancer: two diseases with obesity as a common risk factor
Garg, S. K., Maurer, H., Reed, K., & SELAGAMSETTY, R. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12124 · Cited by 281
“There is also some evidence to suggest that people with diabetes may be less responsive to chemotherapy than people without diabetes [73].”
BackgroundStorozhuk, Y., Hopmans, S., Sanli, T., Barron, C. C., Tsiani, E., Cutz, J.-C., Pond, G. R., Wright, J. R., Singh, G., & Tsakiridis, T. K. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.187 · Cited by 276
“Retrospective analysis suggested that MET may enhance chemotherapy responses in women with breast cancer (Jiralerspong et al, 2009).”
BackgroundUnderstanding obesity and endometrial cancer risk: opportunities for prevention
Schmandt, R. E., Iglesias, D. A., Co, N. N., & Lu, K. H. (2011) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2011.05.042 · Cited by 280
Metformin Use and All-Cause and Prostate Cancer–Specific Mortality Among Men With Diabetes
Margel, D., Urbach, D. R., Lipscombe, L. L., Bell, C. M., Kulkarni, G. S., Austin, P. C., & Fleshner, N. E. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.7043 · Cited by 275
Impact of Age, Sex, and Comorbidity on Cancer Therapy and Disease Progression
Pal, S. K., & Hurria, A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.0579 · Cited by 266
“plete response with neoadjuvant chemotherapy among diabetic patients taking metformin as compared with nondiabetic patients.(76)”
ResultJanzer, A., German, N. J., Gonzalez-Herrera, K. N., Asara, J. M., Haigis, M. C., & Struhl, K. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409844111 · Cited by 273
“Toxicol Appl Pharmacol 233(2):203–210.”
MethodInfluentialMetformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes
Dutta, S., Shah, R., Singhal, S., Dutta, S. B., Bansal, S., Sinha, S., & Haque, M. (2023) · Drug Design Development and Therapy · doi:10.2147/dddt.s409373 · Cited by 296
“IGF1R and MRP1 (“Multidrug Resistance-Associated Protein 1”) co-expression is linked to a poorer response to anticancer drugs.(130)”
BackgroundResultPancreatogenic Diabetes: Special Considerations for Management
Cui, Y., & Andersen, D. K. (2011) · Pancreatology · doi:10.1159/000329188 · Cited by 256
“in pancreatic cancer patients, metformin has also been shown to have anti-cancer effectiveness in diabetic breast cancer patients [”
BackgroundRomero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H., & Grossman, L. I. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.06.003 · Cited by 253
Energy Balance, Host-Related Factors, and Cancer Progression
Hursting, S. D., & Berger, N. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.27.9935 · Cited by 257
“In a recent study of patients receiving neoadjuvant chemotherapy for breast cancer, a group of women who were also treated with metformin for coexisting diabetes showed a greater rate of pathologic response.(136) Agents such as metformin that indirectly target the mTOR complex hold great promise, because mTOR serves a…”
BackgroundPierotti, M. A., Berrino, F., Gariboldi, M., Melani, C. C., Mogavero, A., Negri, T., Pasanisi, P., & Pilotti, S. (2012) · Oncogene · doi:10.1038/onc.2012.181 · Cited by 253
Effect of Metformin vs Placebo on Invasive Disease–Free Survival in Patients With Breast Cancer
Goodwin, P. J., Chen, B. E., Gelmon, K. A., Whelan, T. J., Ennis, M., Lemieux, J., Ligibel, J. A., Hershman, D. L., Mayer, I. A., Hobday, T. J., et al. (2022) · JAMA · doi:10.1001/jama.2022.6147 · Cited by 247
Metformin and Other Biguanides in Oncology: Advancing the Research Agenda
Pollak, M. (2010) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0175 · Cited by 240
Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study
Niraula, S., Dowling, R. J. O., Ennis, M., Chang, M. C., Done, S. J., Hood, N., Escallón, J., Leong, W. L., McCready, D. R., Reedijk, M., et al. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2223-1 · Cited by 238
“In a retrospective analysis, diabetic breast cancer patients taking metformin had a significantly higher rate of response to neoadjuvant chemotherapy than those taking other antidiabetic drugs [5].”
BackgroundMetformin Targets Central Carbon Metabolism and Reveals Mitochondrial Requirements in Human Cancers
Liu, X., Romero, I. L., Litchfield, L. M., Lengyel, E. R., & Locasale, J. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.005 · Cited by 229
“Epidemiological data have strongly associated metformin usage with improved cancer outcomes in multiple cohorts in numerous different cancers, including OvCa (Decensi et al., 2010; Evans et al., 2005; Ezewuiro et al., 2016; Jiralerspong et al., 2009; Libby et al., 2009; Romero et al., 2012; Wright and Stanford, 2009).”
BackgroundInfluentialLi, L., Han, R., Xiao, H., Lin, C., Wang, Y., Liu, H., Li, K., Chen, H., Sun, F., Yang, Z., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2613 · Cited by 240
“The patients with diabetes with breast cancer receiving metformin and neoadjuvant chemotherapy had a higher pathologic complete response rate than did those not receiving metformin (24).”
BackgroundObesity and cancer pathogenesis
Berger, N. A. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12416 · Cited by 241
Zheng, L., Yang, W. K., Wu, F., Wang, C., Yu, L., Tang, L., Qiu, B., Li, Y., Guo, L., Wu, M.-C., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0203 · Cited by 222
“Interestingly, metformin also increased chemosensitivity of HCC cells, consistent with observation in clinical study and mouse xenografts models (22, 23).”
ResultBrownfoot, F. C., Hastie, R., Hannan, N. J., Cannon, P., Tuohey, L., Parry, L. J., Senadheera, S., Illanes, S. E., Kaitu’u-Lino, T. J., & Tong, S. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.12.019 · Cited by 222
Metformin and breast cancer risk: a meta-analysis and critical literature review
Col, N. F., Ochs, L. A., Springmann, V., Aragaki, A. K., & Chlebowski, R. T. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2170-x · Cited by 217
Sanli, T., Rashid, A., Liu, C., Harding, S. M., Bristow, R. G., Cutz, J.-C., Singh, G., Wright, J. R., & Tsakiridis, T. K. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.03.005 · Cited by 216
Deng, X., Wang, S., Deng, A., Liu, B., Edgerton, S. M., Lind, S. E., Wahdan-Alaswad, R. S., & Thor, A. D. (2012) · Cell Cycle · doi:10.4161/cc.11.2.18813 · Cited by 212
“It has been shown to reduce pro-growth signaling through EGFR, MAPK and Akt pathway.(29,30,46) It also has been shown to inhibit mammary tumorigenesis using a variety of model systems (reviewed in detail in ref.”
BackgroundMethodDiabetes, Metformin, and Breast Cancer in Postmenopausal Women
Chlebowski, R. T., McTiernan, A., Wactawski‐Wende, J., Manson, J. E., Aragaki, A. K., Rohan, T. E., Ipp, E., Kaklamani, V., Vitolins, M. Z., Wallace, R. B., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.39.7505 · Cited by 218
Metformin: A Therapeutic Opportunity in Breast Cancer
Gonzalez-Angulo, A. M., & Meric‐Bernstam, F. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1805 · Cited by 211
Self-citationAssociation between Metabolic Syndrome and Cancer
Uzunlulu, M., Çaklılı, Ö. T., & Oğuz, A. (2016) · Annals of Nutrition and Metabolism · doi:10.1159/000443743 · Cited by 220
Diabetes, cancer, and metformin: connections of metabolism and cell proliferation
Gallagher, E. J., & LeRoith, D. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06285.x · Cited by 208
Metformin in Breast Cancer: Time for Action
Goodwin, P. J., Ligibel, J. A., & Stambolic, V. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.1630 · Cited by 199
Chen, G., Xu, S., Renko, K., & Derwahl, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1754 · Cited by 196
“Furthermore, retrospective analysis of data from neoadjuvant breast cancer therapy indicated that metformin may potentiate the effect of chemotherapy (7).”
BackgroundMetabolic alterations and targeted therapies in prostate cancer
Flavin, R., Zadra, G., & Loda, M. F. (2010) · The Journal of Pathology · doi:10.1002/path.2809 · Cited by 178
“Recent evidence indicates that: (a) diabetics under treatment with metformin show a reduced cancer incidence [95] and cancer-related mortality, compared to patients exposed to sulphonylureas or insulin [96]; (b) metformin use is associated with a 44% risk reduction in PCa cases compared to controls in Caucasian men [9…”
p53 Regulation of Metabolic PathwaysPreprint
Gottlieb, E., & Vousden, K. H. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001040 · Cited by 189
Romero, I. L., McCormick, A., McEwen, K. A., Park, S., Karrison, T. G., Yamada, S. D., Pannain, S., & Lengyel, E. R. (2011) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e3182393ab3 · Cited by 178
Goodwin, P. J., Stambolic, V., Lemieux, J., Chen, B. E., Parulekar, W. R., Gelmon, K. A., Hershman, D. L., Hobday, T. J., Ligibel, J. A., Mayer, I. A., et al. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-1224-1 · Cited by 178
“Additional support for a role of metformin in breast cancer outcomes comes from a retrospective clinical study that reported significantly increased pathologic complete response (pCR) rates to standard neoadjuvant chemotherapy in diabetic breast cancer patients who were receiving metformin (24% pCR) compared to diabet…”
ResultBayraktar, S., Hernadez‐Aya, L. F., Lei, X., Meric‐Bernstam, F., Litton, J. K., Hsu, L., Hortobagyi, G. N., & Gonzalez‐Angulo, A. M. (2012) · Cancer · doi:10.1002/cncr.26439 · Cited by 176
“Age at diagnosis, y Median (range) 53 (30-67) 51 (35-80) 48 (21-87)”
Metformin selectively affects human glioblastoma tumor-initiating cell viability
Würth, R., Pattarozzi, A., Gatti, M., Bajetto, A., Corsaro, A., Parodi, A., Sirito, R., Massollo, M., Marini, C., Zona, G., et al. (2012) · Cell Cycle · doi:10.4161/cc.23050 · Cited by 176
“Subsequently, high complete response rate in diabetic breast cancer patients treated with metformin, according to neo-adjuvant protocols, was reported.(19) It was proposed that metformin activity was not due to indirect effects related to the antagonism of pro-tumoral effects induced by diabetic hyperglycemia,(43) but…”
BackgroundMartinez‐Outschoorn, U., Goldberg, A. F., Zhao, L., Ko, Y., Flomenberg, N., Wang, C., Pavlides, S., Pestell, R. G., Howell, A., Sotgia, F., et al. (2011) · Cancer Biology & Therapy · doi:10.4161/cbt.12.10.17780 · Cited by 180
“In a retrospective study examining the rates of pathologic complete remission (pCR) after neoadjuvant chemotherapy, it was found that 24% of diabetic patients taking metformin achieved pCR, compared with 8% of those who were not receiving metformin.(77) In summary, the use of metformin in diabetic patients is associat…”
ResultHardie, D. G. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390001 · Cited by 180
Mao‐Ying, Q., Kavelaars, A., Krukowski, K., Huo, X., Zhou, W., Price, T. J., Cleeland, C. S., & Heijnen, C. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100701 · Cited by 174
“In a retrospective study in breast cancer patients with diabetes, patients treated with metformin had higher complete pathologic response rates to neoadjuvant therapy than diabetic patients treated with other antidiabetic drugs [27].”
BackgroundAnisimov, V. N., Egormin, P. A., Piskunova, T. S., Popovich, I. G., Tyndyk, M. L., Yurova, M. N., Zabezhinski, M. A., Anikin, I. V., Karkach, A. S., & Romanyukha, A. A. (2010) · Cell Cycle · doi:10.4161/cc.9.1.10407 · Cited by 146
PolyMetformin combines carrier and anticancer activities for in vivo siRNA delivery
Zhao, Y. D., Wang, W., Guo, S., Wang, Y., Miao, L., Xiong, Y., & Huang, L. (2016) · Nature Communications · doi:10.1038/ncomms11822 · Cited by 173
Obesity, diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients
Jiralerspong, S., Kim, E. S., Dong, W., Feng, L., Hortobágyi, G. N., & Giordano, S. H. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt224 · Cited by 167
Self-citationImpact of Metformin on the Prognosis of Cirrhosis Induced by Viral Hepatitis C in Diabetic Patients
Nkontchou, G., Cosson, E., Aout, M., Mahmoudi, A., Bourcier, V., Charif, I., Ganne‐Carrié, N., Grando–Lemaire, V., Vicaut, É., Trinchet, J., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2415 · Cited by 167
“Furthermore, women with T2D receiving neoadjuvant chemotherapy for breast cancer were reported to have a higher complete response rate if they were using metformin as compared with women not using metformin (17).”
BackgroundDiabetes increases the risk of breast cancer: a meta-analysis
Hardefeldt, P. J., Edirimanne, S., & Eslick, G. D. (2012) · Endocrine Related Cancer · doi:10.1530/erc-12-0242 · Cited by 164
“New evidence has also indicated that metformin use may improve prognosis (Jiralerspong et al. 2009).”
BackgroundTan, B., Yao, W., Ge, J., Peng, X., Du, X., Zhang, R., Yao, B., Xie, K., Li, L., Dong, H., et al. (2011) · Cancer · doi:10.1002/cncr.26151 · Cited by 161
Metadata
- Authors
- Jiralerspong, S., Palla, S. L., Giordano, S. H., Meric-Bernstam, F., Liedtke, C., Barnett, C. M., Hsu, L., Hung, M.-C., Hortobagyi, G. N., & Gonzalez-Angulo, A. M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From the Departments of Breast Medical Oncology, Biochemistry and Molecular Biology, Quantitative Sciences, Surgical Oncology, Pharmacy, Molecular and Cellular Oncology, and Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and the Department of Gynecology and Obstetrics, University of Muenster, Muenster, Germany.
- Venue
- Journal of Clinical Oncology
- Published
- 2009-07-10
- Volume
- 27
- Issue
- 20
- Pages
- 3297-3302
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC2736070
- OpenAlex
- W2171998898
- Cited by
- 880
- References
- 42
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 18 · 2023: 34 · 2022: 31 · 2021: 51 · 2020: 43 · 2019: 60 · 2018: 34 · 2017: 42 · 2016: 54 · 2015: 53 · 2014: 73 · 2013: 97 · 2012: 76
- FWCI
- 35.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Association for Cancer Research
- Breast Cancer Research Foundation
- Amgen
- American Society of Clinical Oncology
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (5k23ca121994-03)
- National Cancer Institute (1K23CA121994-01), K23-CA121994, 1K23CA121994)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- metformin, breast cancer, diabetes mellitus, neoadjuvant chemotherapy, pathological complete response, predictors of treatment response
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Diabetes Mellitus, Female, Humans, Hypoglycemic Agents, Metformin, Middle Aged, Remission Induction, Multivariate Analysis, Logistic Models, Survival Analysis, Treatment Outcome, Neoadjuvant Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
