Type 2 diabetes, breast cancer specific and overall mortality: associations by metformin use and modification by race, body mass, estrogen receptor, and menopausal status Open Access
Lee, Kyung Na (Spring 2018)
Abstract
Type 2 diabetes (T2D) has been associated with increased mortality among women diagnosed with breast cancer. While previous investigations regarding T2D and all-cause mortality have shown consistently increased mortality rates, the association between T2D and breast cancer-specific (BCS) mortality is unresolved. In addition, depending on certain prognostic characteristics─ such as race, BMI, estrogen receptor (ER), and menopausal status, heterogeneous outcomes may exist. The purpose of this paper was to examine the effect of T2D on both mortality rates and effect measure modification (EMM) by select prognostic factors. We additionally explored the association between metformin and mortality following breast cancer diagnosis. A retrospective cohort study was conducted between January 1, 2002 and December 31, 2008 from Emory University Hospitals among Non-Hispanic black and Non-Hispanic white women who had confirmed diagnosis of stage I-III invasive breast cancer and known diabetes status (T2D: n= 73; non-T2D: n= 514). Patients were followed until January 1, 2018 and were assessed for BCS and all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Compared to non-T2D, T2D had almost 2-fold increase in BCS mortality after adjusting for age at diagnosis, BMI, race, and comorbidities (HR=1.97; 95% CI 1.02, 3.82). Though attenuated, the increased hazard of death was also observed for all-cause mortality (HR=1.65; 95% CI 1.01, 2.69). However, interactions between T2D and mortality was not evident on multiplicative or additive scales for any of the factors considered. T2D without metformin had substantially higher HR compared to non-diabetics, a 4-fold increase in BCS mortality (HR=3.77; 95% CI 1.70, 8.36), whereas the association among T2D with metformin was modest (HR= 1.41; 95% CI 0.49, 4.03). This result may indicate a potential beneficial effect of metformin therapy on breast cancer mortality. In conclusion, among women with breast cancer T2D is associated with increased BCS and all-cause mortality. Implementing early T2D intervention program during the initial diagnosis of breast cancer may prevent excess risk of deaths.
Table of Contents
CHAPTER I: BACKGROUND/LITERATURE REVIEW... 1
1.1 Breast Cancer Epidemiology. 1
1.2 Risk Factors. 2
1.3 Obesity and Breast Cancer: Epidemiology and Mechanisms. 3
1.4 Obesity and Type 2 Diabetes. 4
1.5 Type 2 Diabetes and Breast Cancer Mortality. 6
1.6 Type 2 Diabetes and Breast Cancer: Potential Effect Measure Modifiers. 6
1.7 Type 2 Diabetes Medications and Breast Cancer 7
1.8 Study Aims. 8
CHAPTER II: TYPE 2 DIABETES, BREAST CANCER SPECIFIC AND OVERALL MORTALITY: ASSOCIATIONS BY METFORMIN USE AND MODIFICATION BY RACE, BODY MASS, ESTROGEN RECEPTOR, AND MENOPAUSAL STATUS. 9
2.1 Abstract 9
2.2 Introduction. 10
2.3 Methods. 11
2.4 Results. 14
2.5 Discussion. 17
2.6 REFERENCES. 22
2.7 TABLES. 33
2.8 FIGURES. 38
CHAPTER III: SUMMARY, PUBLIC HEALTH IMPLICATIONS, POSSIBLE FUTURE DIRECTIONS. 42
4 APPENDICES. 44
4.1 Appendix A.. 44
4.2 Appendix B.. 46
4.3 Appendix C.. 47
4.4 Appendix D.. 48
4.5 Appendix E. 49
4.4 Appendix F. 51
4.5 Appendix G.. 53
4.6 Appendix H.. 55
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