Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes.
BACKGROUND
Metformin use has recently been observed to decrease both the rate and mortality of breast cancer. Our study was aim to determine whether metformin use is associated with survival in diabetic breast cancer patients by breast cancer subtype and systemic treatment.


METHODS
Data from the Asan Medical Center Breast Cancer Database from 1997 to 2007 were analyzed. The study cohort comprised 6,967 nondiabetic patients, 202 diabetic patients treated with metformin, and 184 diabetic patients that did not receive metformin. Patients who were divided into three groups by diabetes status and metformin use were also divided into four subgroups by hormone receptor and HER2-neu status.


RESULTS
In Kaplan-Meier analysis, the metformin group had a significantly better overall and cancer specific survival outcome compared with non metformin diabetic group (P <0.005 for both). There was no difference in survival between the nondiabetic and metformin groups. In multivariate analysis, Compared with metformin group, patients who did not receive metformin tended to have a higher risk of metastasis with HR 5.37 (95 % CI, 1.88 to 15.28) and breast cancer death with HR 6.51 (95 % CI, 1.88 to 15.28) on the hormone receptor-positive and HER2-negative breast cancer. The significant survival benefit of metformin observed in diabetic patients who received chemotherapy and endocrine therapy (HR for disease free survival 2.14; 95 % CI 1.14 to 4.04) was not seen in diabetic patients who did not receive these treatments.


CONCLUSIONS
Patients receiving metformin treatment when breast cancer diagnosis show a better prognosis only if they have hormone receptor-positive, HER2-positive tumors. Metformin treatment might provide a survival benefit when added to systemic therapy in diabetic patients.
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. haapybirth@amc.seoul.kr.
Hee Jeong
HJ
Kim
Division of Vascular Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ultrapolymer@hotmail.com.
Hyunwook
H
Kwon
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jjjwonwr@hanmail.net.
Jong Won
JW
Lee
Department of Clinical Epidemiology and Biostatics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. rsvp@amc.seoul.kr.
Hwa Jung
HJ
Kim
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. newstar153@hanmail.net.
Sae Byul
SB
Lee
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. paul0109@naver.com.
Hee Sung
HS
Park
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. guiyun98@gmail.com.
Guiyun
G
Sohn
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. haepary@naver.com.
Yura
Y
Lee
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. spdoctor@naver.com.
Beom Seok
BS
Koh
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. lymbics@hanmail.net.
Jong Han
JH
Yu
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. brdrson@korea.com.
Byung Ho
BH
Son
Division of Breast and Endocrine Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ahnsh@amc.seoul.kr.
Sei Hyun
SH
Ahn
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D003920:Diabetes Mellitus / Q000188:drug therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D047368:Tumor Burden
D008687:Metformin; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone