Objective: The purpose of this retrospective study was to investigate the effect of metformin on the survival of Chinese breast cancer patients with type 2 diabetes mellitus (T2DM) after surgery. Methods: A total of 3,553 primary breast cancer patients who underwent surgery from January 2010 to December 2013 was enrolled in this study. The patients were divided as metformin group (312 cases), insulin group (79 cases) and non-diabetes group (3139 cases) according medication treatment. The median follow-up time was 85 months. Overall survival (OS) and disease-free survival (DFS) after tumor removal were estimated with the Kaplan-Meier method followed by a log-rank test for evaluating three groups differences. Multivariate Cox proportional hazards regression model was applied to estimate the relationship between metformin and prognosis of breast cancer patients with T2DM. Results: Clinical and pathological features of three group patients were matched. There was a significant survival difference among metformin group, insulin group and non-diabetes group, 5-year OS was 97.1%, 73.3%, 87.3%, and 5-year DFS was 96.1%, 73.0%, 85.8% respectively (P <0.05). Through the Kaplan-Meier curve and Cox multivariate analysis, metformin was significantly associated with better OS [hazard ratio (HR) 0.386, 95% confidence interval (CI) 0.248-0.601; P =0.000] and DFS (HR 0.384, 95% CI 0.247-0.598; P = 0.000). Conclusion: Metformin might have a good impact on the survival of breast cancer patients with T2DM. However, due to the limitations of the retrospective design in this study, prospective studies are needed to confirm our results.

Multivariable analyses of OS and DFS in all breast cancer patients
OSDFS
HR(95.0%CI)PHR(95.0%CI)P
Age at diagnosis  0.003  0.013 
≤55 years   
>55 years 1.302(1.094-1.549)  1.247(1.048-1.484)  
BMI  0.000  0.000 
<25   
25-30 1.280(1.070-1.532)  1.300(1.087-1.556)  
≥30 1.696(1.300-2.213)  1.753(1.344-2.286)  
Tumour size  0.000  0.000 
≤2cm   
>2cm,≤5cm 1.261(1.053-1.511)  1.259(1.051-1.507)  
>5cm 2.281(1.602-3.247)  2.234(1.569-3.182)  
Uncertain 1.248(0.897-1.736)  1.241(0.892-1.726)  
Lymph node metastasis  0.000  0.000 
  
1-3 2.684(2.158-3.338)  2.716(2.184-3.376)  
4-9 3.960(3.072-5.105)  4.096(3.178-5.280)  
≥10 9.264(7.339-11.695)  9.837(7.782-12.433)  
ER status  0.012  0.016 
Negative   
Positive 0.738(0.563-0.967)  0.738(0.563-0.967)  
Unknown   
PR status  0.025  0.017 
Negative   
Positive 0.745(0.580-0.958)  0.730(0.569-0.938)  
Unknown   
Ki-67  0.009  0.007 
Low   
High 1.255(1.017-1.547)  1.285(1.042-1.584)  
Uncertain   
Groups  0.000  0.000 
Non-diabetes   
Metformin 0.386 (0.248-0.601)  0.384(0.247-0.598)  
Insulin 1.307(0.848-2.014)  1.205(0.781-1.858)  
Multivariable analyses of OS and DFS in all breast cancer patients
OSDFS
HR(95.0%CI)PHR(95.0%CI)P
Age at diagnosis  0.003  0.013 
≤55 years   
>55 years 1.302(1.094-1.549)  1.247(1.048-1.484)  
BMI  0.000  0.000 
<25   
25-30 1.280(1.070-1.532)  1.300(1.087-1.556)  
≥30 1.696(1.300-2.213)  1.753(1.344-2.286)  
Tumour size  0.000  0.000 
≤2cm   
>2cm,≤5cm 1.261(1.053-1.511)  1.259(1.051-1.507)  
>5cm 2.281(1.602-3.247)  2.234(1.569-3.182)  
Uncertain 1.248(0.897-1.736)  1.241(0.892-1.726)  
Lymph node metastasis  0.000  0.000 
  
1-3 2.684(2.158-3.338)  2.716(2.184-3.376)  
4-9 3.960(3.072-5.105)  4.096(3.178-5.280)  
≥10 9.264(7.339-11.695)  9.837(7.782-12.433)  
ER status  0.012  0.016 
Negative   
Positive 0.738(0.563-0.967)  0.738(0.563-0.967)  
Unknown   
PR status  0.025  0.017 
Negative   
Positive 0.745(0.580-0.958)  0.730(0.569-0.938)  
Unknown   
Ki-67  0.009  0.007 
Low   
High 1.255(1.017-1.547)  1.285(1.042-1.584)  
Uncertain   
Groups  0.000  0.000 
Non-diabetes   
Metformin 0.386 (0.248-0.601)  0.384(0.247-0.598)  
Insulin 1.307(0.848-2.014)  1.205(0.781-1.858)  

BMI, body mass index; ER, estrogen receptor; PR, progesterone receptor.

Citation Format: Tianli Hui, Chao Shang, Zhenchuan Song. Metformin improves the survival in Chinese early invasive breast cancer patients with type 2 diabetes mellitus [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-19.