Diabetes mellitus and prognosis in women with breast cancer

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Abstract

Background:

Diabetes mellitus is associated with an increased risk of breast cancer, but studies of the effects of diabetes on the prognosis of women with breast cancer have yielded inconsistent findings. The present meta-analysis aimed to investigate the impact of preexisting diabetes on the prognosis in terms of overall survival (OS), disease-free survival (DFS), and relapse-free period (RFP) in women with breast cancer.

Methods:

We searched the Embase and PubMed databases until June 2016 for cohort or case–control studies assessing the impact of diabetes on the prognosis of women with breast cancer. The pooled multivariate adjusted hazard ratio (HR) and their 95% confidence intervals (CIs) for OS, DFS, and RFP were used to analyze the impact of diabetes on the prognosis of breast cancer patients.

Results:

Seventeen studies involving 48,315 women with breast cancer met our predefined inclusion criteria. Meta-analysis showed that the pooled adjusted HR was 1.51 (95% CI 1.34–1.70) for OS and 1.28 (95% CI 1.09–1.50) for DFS in breast cancer patients with diabetes compared to those without diabetes. However, RFP did not differ significantly between patients with and without diabetes (HR 1.42; 95% CI 0.90–2.23).

Conclusions:

The present meta-analysis suggests that preexisting diabetes is independently associated with poor OS and DFS in female breast cancer patients. However, the impact of diabetes on RFP should be further verified. More prospective studies are warranted to investigate whether appropriate glycemic control with modification of antihyperglycemic agents can improve the prognosis of female breast cancer patients with diabetes.

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Most cited references 28

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Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older.

R Yancik, M N Wesley, L A Ries … (2001)

Postmenopausal women aged 55 years and older have 66% of incident breast tumors and experience 77% of breast cancer mortality, but other age-related health problems may affect tumor prognosis and treatment decisions. To document the comorbidity burden of postmenopausal breast cancer patients and evaluate its relationship with age on disease stage, treatment, and early mortality. Data were collected on breast cancer patients' comorbidities by retrospective hospital medical records review and merged with information on patients' tumor characteristics collected from 6 regional National Cancer Institute Surveillance, Epidemiology, and End Results cancer registries. Patients were followed up until death or for 30 months from breast cancer diagnosis. Population-based random sample of 1800 postmenopausal breast cancer patients diagnosed in 1992 stratified by 3 age groups: 55 to 64 years, 65 to 74 years, and 75 years and older. Extent of disease, therapy received, comorbidity, cause of death, and survival. Seventy-three percent (1312 of 1800) of the sample was diagnosed with stage I and II breast cancer, 10% (n = 188) with stage III and IV breast cancer, and 17% (n = 300) did not have a stage assignment. Of the 1017 patients with stage I and stage II node-negative breast cancer, 95% received therapy in agreement with the National Institutes of Health consensus statement recommendation for early-stage breast cancer. Patients in older age groups were less likely to receive therapy consistent with the consensus statement (P<.001), and women aged 70 years and older were significantly less likely to receive axillary lymph node dissection as determined by logistic regression analysis (P<.01). Diabetes, renal failure, stroke, liver disease, a previous malignant tumor, and smoking were significant in predicting early mortality in a statistical model that included age and disease stage. Breast cancer was the underlying cause of death for 135 decedents (51.3%). Heart disease (n = 45, 17.1%) and previous cancers (n = 22, 8.4%) were the next major underlying causes. In the 30-month follow-up period, 263 patients (15%) died. Patient care decisions occur in the context of breast cancer and other age-related conditions. Comorbidity in older patients may limit the ability to obtain prognostic information (ie, axillary lymph node dissection), tends to minimize treatment options (eg, breast-conserving therapy), and increases the risk of death from causes other than breast cancer.

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Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis.

H R Haak, M W Dercksen, Chantal Heijnen … (2007)

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population-based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow-up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow-up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox-regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40-1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes. (c) 2007 Wiley-Liss, Inc.

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Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes.

N Kurshan, Derek LeRoith, A Pennisi … (2010)

Epidemiologic studies suggest that type 2 diabetes (T2D) increases breast cancer risk and mortality, but there is limited experimental evidence supporting this association. Moreover, there has not been any definition of a pathophysiological pathway that diabetes may use to promote tumorigenesis. In the present study, we used the MKR mouse model of T2D to investigate molecular mechanisms that link T2D to breast cancer development and progression. MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. Tumor-promoting effects of T2D in the models were reversed by pharmacological blockade of IR/IGF-IR signaling by the small-molecule tyrosine kinase inhibitor BMS-536924. Our findings offer compelling experimental evidence that T2D accelerates mammary gland development and carcinogenesis,and that the IR and/or the IGF-IR are major mediators of these effects.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: December 2016

Publication date (Electronic): 09 December 2016

Volume: 95

Issue: 49

Electronic Location Identifier: e5602

Affiliations

[a ]Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing

[b ]Department of Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong

[c ]Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Author notes

[∗ ]Correspondence: Guo-Sheng Ren, Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China (e-mail: rengs726@ 123456126.com ).

Article

Publisher ID: MD-D-16-04738 Accession ID: 05602

DOI: 10.1097/MD.0000000000005602

PMC ID: 5266055

PubMed ID: 27930583

SO-VID: adf497b2-d645-46f4-b8ef-8e25aa21384a

License:

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

History

Date received : 15 July 2016

Date revision received : 11 November 2016

Date accepted : 15 November 2016

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Keywords: breast cancer,diabetes mellitus,meta-analysis,prognosis

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Keywords: breast cancer, diabetes mellitus, meta-analysis, prognosis

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Diabetes mellitus and prognosis in women with breast cancer : A systematic review and meta-analysis

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Karger: Oncology

Most cited references 28

Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older.

Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis.

Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes.

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Cited by 38

Most referenced authors 889