The impact of diabetes on survival following breast cancer
Abstract
Purpose It has been suggested that type 2 diabetes may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The purpose of this study was to examine the impact of diabetes on survival following breast cancer.Methods Using population-based health databases from Ontario, Canada, this retrospective cohort study compared deaths between women with breast cancer aged 55-79 years with diabetes and without diabetes. Women were followed for all cause mortality from breast cancer diagnosis until March 31st 2006.Results Of the 6,107 women with breast cancer, 1,011 had diabetes and 5,096 did not have diabetes. Women with diabetes were slightly older, were more likely to reside in a lower income neighborhood, and had greater comorbidity compared to women without diabetes. After a mean follow-up of 5.0 years and adjustment for age, prior mammograms and other covariates, mortality following breast cancer was significantly higher among women with versus without diabetes (hazard ratio, HR 1.39, 95% confidence interval, CI 1.22-1.59, P < 0.0001). The effect of diabetes on mortality was comparable to that seen in women with diabetes without breast cancer over a 7-year follow-up.Conclusion This study found that diabetes was associated with a close to 40% increase in mortality within the first 5 years following breast cancer, which was similar to that seen in women with diabetes without breast cancer. These findings suggest that early survival following breast cancer is reduced in women with diabetes, possibly due to diabetes-related causes.
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In one study, 5-year mortality rates were significantly higher (hazard ratio 1.39) in patients diagnosed with both breast cancer and diabetes than in comparable breast cancer patients without diabetes.
“in one study, 5-year mortality rates were significantly higher (hazard ratio 1.39) in patients diagnosed with both breast cancer and diabetes than in comparable breast cancer patients without diabetes (9).”
From Diabetes and Cancer (2010) · cites this paper as [9]
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“[13] also found that the increased overall mortality in breast cancer patients with diabetes was similar to that in diabetic women without breast cancer.”
ResultMetformin Targets Glucose Metabolism in Triple Negative Breast Cancer
Wahdan-Alaswad, R. S., Edgerton, S. M., Salem, H. S., & Thor, A. D. (2018) · Journal of Oncology Translational Research · doi:10.4172/2476-2261.1000129 · Cited by 50 · see citing works
“These chronic diseases are also independently associated with a worse prognosis and higher diseaseassociated mortality for these women [11,12].”
BackgroundDiabetes, diabetes treatment and breast cancer prognosis
Luo, J., Virnig, B. A., HENDRYX, M. S., Wen, S., Chelebowski, R., Chen, C., Rohan, T. E., Tinker, L. F., Wactawski‐Wende, J., Lessin, L. S., et al. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3146-9 · Cited by 49 · see citing works
“There is also convincing evidence that overall mortality following breast cancer is significantly higher in diabetic women with breast cancer than their non-diabetic counterparts [12, 18, 22, 34].”
BackgroundInfluence of diabetes mellitus on mortality in breast cancer patients
Zhou, Y., Zhang, X., Gu, C., & Xia, J. (2014) · ANZ Journal of Surgery · doi:10.1111/ans.12877 · Cited by 44 · see citing works
The Impact of Diabetes Mellitus on Prognosis of Early Breast Cancer in Asia
Chen, T. W., Shao, Y., Shau, W., Lin, Z., Lu, Y., Chen, H., Kuo, R. N.-C., Cheng, A., & Lai, M. (2012) · The Oncologist · doi:10.1634/theoncologist.2011-0412 · Cited by 43 · see citing works
“DM is associated with other comorbidities, such as metabolic disorder, cardiovascular disease, and renal disease [7, 14, 15], and thus, the prognostic influence of DM is affected when other comorbidities are present [9, 14, 16].”
BackgroundGlucose metabolism disorders in cancer patients in a Chinese population
Ya-shi, Z., Feng, L., Tang, S., Li, W.-G., Xu, M., Liu, T., Zhou, Y.-F., Ma, Y., Zhang, Y., & Pu, X.-M. (2009) · Medical Oncology · doi:10.1007/s12032-009-9189-9 · Cited by 39 · see citing works
“Presently, plenty of studies investigating the relationships between malignancy and DM have been reported, but most of them were focused on pancreatic cancer [33, 41, 42], breast cancer [10, 39, 43–45], prostatic carcinoma [38, 46– 50], or colorectal cancer [36, 37, 51, 52], whereas the evidence of changed glucose met…”
BackgroundObesity and Angiolymphatic Invasion in Primary Breast Cancer
Gillespie, E. F., Sorbero, M. E. S., Hanauer, D. A., Sabel, M. S., Herrmann, E., Weiser, L. J., Jagielski, C. H., & Griggs, J. J. (2009) · Annals of Surgical Oncology · doi:10.1245/s10434-009-0797-6 · Cited by 39 · see citing works
Wang, Y., Gao, D., Chen, Y., Hu, G., Liu, H., & Jiang, Y. (2016) · RSC Advances · doi:10.1039/c6ra12131d · Cited by 38 · see citing works
Zelenko, Z., Gallagher, E. J., Tobin‐Hess, A., Belardi, V., Rostoker, R., Blank, J., Dina, Y., & LeRoith, D. (2016) · Oncogene · doi:10.1038/onc.2016.305 · Cited by 38 · see citing works
“Of these factors, hyperinsulinemia has emerged to be a key player and has been associated with decreased breast cancer survival and recurrence free survival (6, 7).”
BackgroundWei, M., Duan, P., Wang, Z., Ding, M., & Tu, P. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7420 · Cited by 38 · see citing works
“In addition, accumulating data suggest that diabetes and its complications can adversely affect cancer therapy (8) and increase mortality (9), thus affecting the outcome of breast cancer patients (10,11).”
BackgroundInsulin priming effect on estradiol-induced breast cancer metabolism and growth
Wairagu, P. M., Phan, A. N. H., Kim, M., Han, J., Kim, H.-W., Choi, J.-W., Kim, K. W., Cha, S., Park, K. H., & Jeong, Y. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1016660 · Cited by 37 · see citing works
“Insulin resistance arising from chronic hyperinsulinemia results in Type II diabetes, a metabolic disorder known as a poor prognostic marker for breast cancer and for being associated with an approximately 40% increase in mortality in the first 5 y with breast cancer diagnosis.(5) Shanik et al.”
BackgroundResultDurrani, I. A., Bhatti, A., & John, P. C. L. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02040-5 · Cited by 36 · see citing works
“For instance, studies tracking death in breast cancer patients reported an increasing trend for women with diabetes, and also supported a stronger independent link with prognosis as compared to breast cancer risk [51], which can be explained by higher insulin levels, late diagnosis, less aggressive treatment plan or d…”
BackgroundPre-diagnosis blood glucose and prognosis in women with breast cancer
Monzavi‐Karbassi, B., Gentry, R. W., Kaur, V., Siegel, E. R., Jousheghany, F., Medarametla, S., Fuhrman, B. J., Safar, A. M., Hutchins, L. F., & Kieber‐Emmons, T. (2016) · Cancer & Metabolism · doi:10.1186/s40170-016-0147-7 · Cited by 36 · see citing works
“However, the contribution of other factors including the delay in diagnosis, lower use of effective adjuvant therapies, diabetes-prescribed drug use, and diabetes-related comorbidities on observed association between diabetes and breast cancer is not clearly addressed [9–20].”
BackgroundManagement of diabetes in patients with cancer
Jacob, P., & Chowdhury, T. A. (2014) · QJM · doi:10.1093/qjmed/hcu218 · Cited by 35 · see citing works
Anticancer Effect of Metformin in Herceptin-Conjugated Liposome for Breast Cancer
Lee, J., Shin, D. H., & Kim, J. (2019) · Pharmaceutics · doi:10.3390/pharmaceutics12010011 · Cited by 35 · see citing works
Shau, W., Shao, Y., Yeh, Y., Lin, Z., Kuo, R. N.-C., Hsu, C., Hsu, C., Cheng, A., & Lai, M. (2012) · The Oncologist · doi:10.1634/theoncologist.2012-0065 · Cited by 34 · see citing works
Javed, S. R., Skolariki, A., Zameer, M. Z., & Lord, S. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02833-1 · Cited by 32 · see citing works
The Role for Insulin and Insulin-like Growth Factors in the Increased Risk of Cancer in Diabetes
LeRoith, D., Scheinman, E. J., & Bitton-Worms, K. (2011) · Rambam Maimonides Medical Journal · doi:10.5041/rmmj.10043 · Cited by 33 · see citing works
Risk of esophagus cancer in diabetes mellitus: a population-based case-control study in Taiwan
Cheng, K. F., Chen, Y., Lai, S., Tsai, P., & Sung, F. (2012) · BMC Gastroenterology · doi:10.1186/1471-230x-12-177 · Cited by 31 · see citing works
“Discussion Studies investigating the relationship between malignancy and DM have revealed conflicting results on the association between DM and esophagus cancer, and other cancers [8,23-39].”
BackgroundResultIGF-1 and risk of additional breast cancer in the WHEL study
Al‐Delaimy, W. K., Flatt, S. W., Natarajan, L., Laughlin, G. A., Rock, C. L., Gold, E. B., Caan, B. J., Parker, B. A., & Pierce, J. P. (2011) · Endocrine Related Cancer · doi:10.1530/erc-10-0121 · Cited by 31 · see citing works
“2002), and in other studies, women with breast cancer and diabetes had a 40% increase in mortality within 5 years following diagnosis compared to women with breast cancer without diabetes (Lipscombe et al. 2008); and breast cancer survivors with HbA1cR7.”
ResultInfluentialGriffiths, R. I., Danese, M. D., Gleeson, M. L., & Valderas, J. M. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-613 · Cited by 30 · see citing works
“Recently, Peairs and colleagues [2] conducted a systematic review and meta-analysis in which they combined results from 6 studies [6-8,12-14], and found diabetes was associated with a 49% increased risk of death due to all causes.”
BackgroundNicholas, D., Andrieu, G. P., Strissel, K. J., Nikolajczyk, B. S., & Denis, G. V. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2320-0 · Cited by 29 · see citing works
“Epidemiological studies have associated increased risk and mortality in breast cancer with T2D [74–81].”
The female breast and diabetes
Gouveri, E., Παπάνας, Ν., & Maltezos, E. S. (2011) · The Breast · doi:10.1016/j.breast.2011.02.019 · Cited by 28 · see citing works
O-GlcNAcylation of GLI transcription factors in hyperglycemic conditions augments Hedgehog activity
Das, S., Bailey, S. K., Metge, B. J., Hanna, A., Hinshaw, D. C., Mota, M., Forero, A., Chatham, J. C., Samant, R. S., & Shevde, L. A. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0122-8 · Cited by 28 · see citing works
Challenges in the management of people with diabetes and cancer
Chowdhury, T. A., & Jacob, P. (2019) · Diabetic Medicine · doi:10.1111/dme.13919 · Cited by 27 · see citing works
Lee, K. N., Torres, M. A., Troeschel, A. N., He, J., Gogineni, K., & McCullough, L. E. (2020) · PLoS ONE · doi:10.1371/journal.pone.0232581 · Cited by 27 · see citing works
A Novel Metabolic Reprogramming Strategy for the Treatment of Diabetes‐Associated Breast Cancer
Hao, Q., Huang, Z., Li, Q., Liu, D., Wang, P., Wang, K., Li, J., Cao, W., Deng, W., Wu, K., et al. (2022) · Advanced Science · doi:10.1002/advs.202102303 · Cited by 27 · see citing works
Ali, N. M., Besar, R., & Aziz, N. A. A. (2022) · Symmetry · doi:10.3390/sym14101955 · Cited by 25 · see citing works
Metformin and survival in diabetic patients with breast cancer
El-Benhawy, S. A., & Elsheredy, H. (2014) · Journal of the Egyptian Public Health Association · doi:10.1097/01.epx.0000456620.00173.c0 · Cited by 25 · see citing works
Use of Insulin and Mortality from Breast Cancer among Taiwanese Women with Diabetes
Tseng, C.-H. (2015) · Journal of Diabetes Research · doi:10.1155/2015/678756 · Cited by 23 · see citing works
“Because there were only 5 cases of breast cancer mortality in patients with type 1 diabetes mellitus (Table 1 and Figure 1) and the results did not markedly change when only patients with type 2 diabetes mellitus were analyzed in secondary analyses (data not shown), it is believed that the results…”
ResultMcCune, K. R., Bhat‐Nakshatri, P., Thorat, M. A., Nephew, K. P., Badve, S., & Nakshatri, H. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-1530 · Cited by 23 · see citing works
“Hyperinsulinemia is an independent risk factor for breast cancer, and the presence of diabetes in breast cancer patients is linked to a 40% increase in mortality within the first 5 years after diagnosis (25, 46).”
BackgroundHuang, X., He, D., Ming, J., He, Y., Zhou, C., Ren, H., He, X., Wang, C., Jin, J., Liang, J., et al. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-3696-0 · Cited by 23 · see citing works
The Role of Insulin Resistance in Cancer
Subedi, B. K., Bhimineni, C., Modi, S., Jahanshahi, A., Quiza, K., & Bitetto, D. (2025) · Current Oncology · doi:10.3390/curroncol32090477 · Cited by 25 · see citing works
“• Altered IGF-Axis Signaling: Hyperinsulinemia suppresses the hepatic production of IGF-binding proteins (IGFBP-1 and IGFBP-2), which may increase the bioavailability of IGF-1 [20,21].”
Sun, X., Zhang, Q., Kadier, K., Hu, P., Liu, X., Liu, J., Yan, Y., Sun, C., Yau, V., Lowe, S., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1059303 · Cited by 22 · see citing works
“In addition, a growing body of data suggests that diabetes and its complications adversely affect cancer treatment (14) and increase mortality (15), thereby affecting the prognosis of breast cancer patients (16, 17).”
BackgroundLifestyle Interventions for Cardiovascular Risk Reduction in Women with Breast Cancer
Knobf, M. T., & Coviello, J. S. (2012) · Current Cardiology Reviews · doi:10.2174/157340311799960627 · Cited by 22 · see citing works
“Pre-existing diabetes in breast cancer survivors has been associated with increased treatment toxicity and reduced survival [26-28].”
BackgroundTreatment and outcomes in diabetic breast cancer patients
Gold, H. T., Makarem, N., Nicholson, J., & Parekh, N. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-2833-x · Cited by 22 · see citing works
Ma, F.-J., Liu, Z.-B., Qu, L., Wu, J., Shao, Z.-M., Liu, G., & Hao, S. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s71095 · Cited by 21 · see citing works
Hosio, M., Urpilainen, E., Hautakoski, A., Marttila, M., Arffman, M., Sund, R., Ahtikoski, A. M., Puistola, U., Karihtala, P., Jukkola‐Vuorinen, A., et al. (2020) · Acta Oncologica · doi:10.1080/0284186x.2020.1769858 · Cited by 20 · see citing works
Li, J., Wen, W., Liu, Z., Chen, C., Cheng, J., Yiping, G., Changhua, W., De-hua, Y., & Shengrong, S. (2015) · Tumor Biology · doi:10.1007/s13277-015-3380-8 · Cited by 19 · see citing works
“However, patients’ age and the tendency for obesity were both considered to be risk factors for diabetes [7].”
BackgroundTherapeutic effects of metformin in breast cancer: involvement of the immune system?
Schott, S., Bierhaus, A., Schütz, F., Beckhove, P., Schneeweiß, A., Sohn, C., & Domschke, C. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1062-y · Cited by 18 · see citing works
“Starting with a delayed and progressed initial presentation, interference with overlapping comorbidities often aVecting the choice of treatment and eventually a markedly increased mortality [ 6 , 7]. In this context, more recently, the discussion was heated in particular due to new insights into antidiabetics actions…”
BackgroundKhajah, M. A., Khushaish, S., & Luqmani, Y. A. (2022) · PLoS ONE · doi:10.1371/journal.pone.0272449 · Cited by 17 · see citing works
Kinesiophobia among Breast Cancer Survivors One Year after Hospital Treatment
Malchrowicz-Mośko, E. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192114565 · Cited by 17 · see citing works
Lawrence, W. R., Hosler, A. S., Gates, M. A., Leinung, M. C., Zhang, X., Schymura, M. J., & Boscoe, F. P. (2020) · Cancer Epidemiology · doi:10.1016/j.canep.2020.101710 · Cited by 17 · see citing works
Relationship between level of HbA1C and breast cancer
Jousheghany, F., Phelps, J. A., Crook, T. A., & Hakkak, R. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.04.005 · Cited by 17 · see citing works
“Diabetes and cancer are two major public health issues worldwide and many studies have shown that diabetes is related to increased cancer mortality [8,17,18].”
BackgroundYang, H., Wu, C.-Y., Powell, J. D., & Lu, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114030 · Cited by 16 · see citing works
Cardiovascular risk in middle-aged breast cancer survivors: a comparison between two risk models
de Sousa-e-Silva, É. P., Conde, D. M., Costa‐Paiva, L., Martínez, E. Z., & Pinto-Neto, A. M. (2014) · Revista Brasileira Ginecologia e Obstetrícia · doi:10.1590/s0100-720320140050.0002 · Cited by 16 · see citing works
Vigen, C. L. P., Kwan, M. L., John, E. M., Gomez, S. L., Keegan, T. H. M., Lu, Y., Shariff‐Marco, S., Monroe, K. R., Kurian, A. W., Cheng, I. C., et al. (2016) · Cancer Causes & Control · doi:10.1007/s10552-016-0715-8 · Cited by 16 · see citing works
Ji, G., Jin, L., Wang, R., Bai, Y., Yao, Z.-X., Lu, L., Huang, J.-B., Liu, S., Li, H., Wang, Z., et al. (2013) · Medical Oncology · doi:10.1007/s12032-013-0687-4 · Cited by 16 · see citing works
“Up to 16 % of the elderly breast cancer patients additionally suffer from diabetes [4], and it was suggested that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted [5].”
BackgroundTalley, C. H., & Williams, K. P. (2015) · Nursing Clinics of North America · doi:10.1016/j.cnur.2015.05.008 · Cited by 16 · see citing works
- Authors
- Lipscombe, L. L., Goodwin, P. J., Zinman, B., McLaughlin, J. R., & Hux, J. E.
- Affiliations
- Institute for Clinical Evaluative Sciences (CA)
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Sunnybrook Health Science Centre (CA)
- Corresponding author
- Lipscombe, Lorraine L.
- Venue
- Breast Cancer Research and Treatment
- Published
- 2007-07-21
- Volume
- 109
- Issue
- 2
- Pages
- 389-395
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W2025598781
- Cited by
- 176
- References
- 26
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 10 · 2021: 4 · 2020: 18 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 15 · 2015: 13 · 2014: 15 · 2013: 11 · 2012: 14
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- type 2 diabetes, breast cancer, survival, mortality, comorbidities, insulin resistance, hyperinsulinemia, prognosis, women
- MeSH terms
- Aged, Breast Neoplasms, Diabetes Mellitus, Type 2, Female, Humans, Middle Aged, Diabetes Complications, Kaplan-Meier Estimate
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