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. 2015 May 3;17(1):64.
doi: 10.1186/s13058-015-0574-3.

Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes

Hee Jeong Kim  1 , Hyunwook Kwon  2 , Jong Won Lee  3 , Hwa Jung Kim  4 , Sae Byul Lee  5 , Hee Sung Park  6 , Guiyun Sohn  7 , Yura Lee  8 , Beom Seok Koh  9 , Jong Han Yu  10 , Byung Ho Son  11 , Sei Hyun Ahn  12
Affiliations

Metformin increases survival in hormone receptor-positive, HER2-positive breast cancer patients with diabetes

Hee Jeong Kim et al. Breast Cancer Res. .

Abstract

Introduction: 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.

Conclusion: 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.

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Figures

Fig. 1
Fig. 1
Disease-free survival according to diabetes mellitus and metformin treatment among different intrinsic subtypes using immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). (a) Hormone receptor-positive, HER2-negative. (b) Hormone receptor-positive, HER2-positive. (c) Hormone receptor-negative, HER2- positive. (d) Hormone receptor-negative, HER2-negative Adjusted for tumor size (≤2 versus > 2 cm), lymph node status (positive versus negative), ER status, PR status, and HER2-neu status (non-amplification versus amplification). HR, hazard ratio; MET, metformin; DM, diabetes mellitus
Fig. 2
Fig. 2
Disease-free survival according to systemic treatment of breast cancer among nondiabetic patients, diabetic patients receiving metformin, and diabetic patients not receiving metformin. (a) Patients who received chemotherapy. (b). Patients who did not receive chemotherapy. (c) Patients who received endocrine therapy. (d) Patients who did not received endocrine therapy. (e) Patients who did not receive any treatment. (f) Patients who received only chemotherapy. (g) Patients who received endocrine therapy only. (h) Patients who received chemotherapy and endocrine therapy. Adjusted for tumor size (≤2 versus > 2 cm), lymph node status (positive versus negative), estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor-2 (HER2)-neu. status (non-amplification versus amplification). HR, hazard ratio; MET, metformin; DM, diabetes mellitus
Fig. 3
Fig. 3
Recurrence risk of breast cancer according to each prognostic factor. (a) Hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative. (b) Hormone receptor-positive, HER2-positive. (c) Hormone receptor-negative, HER2-positive. (d) Hormone receptor-negative, HER2-negative
Fig. 4
Fig. 4
Breast cancer survival according to diabetes mellitus (DM) and metformin treatment (MET). (a) Overall survival. (b) Cancer-specific survival. (c) Disease-free survival. Adjusted for tumor size (≤2 versus > 2 cm), lymph node status (positive versus negative), estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor-2 (HER2)-neu status (non-amplification versus amplification), chemotherapy and endocrine therapy
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References

    1. Chen WW, Shao YY, Shau WY, Lin ZZ, Lu YS, Chen HM, et al. The impact of diabetes mellitus on prognosis of early breast cancer in Asia. Oncologist. 2012;17:485–91. doi: 10.1634/theoncologist.2011-0412. - DOI - PMC - PubMed
    1. Bowker SL, Richardson K, Marra CA, Johnson JA. Risk of breast cancer after onset of type 2 diabetes: evidence of detection bias in postmenopausal women. Diabetes Care. 2011;34:2542–4. doi: 10.2337/dc11-1199. - DOI - PMC - PubMed
    1. Kaplan MA, Pekkolay Z, Kucukoner M, Inal A, Urakci Z, Ertugrul H, et al. Type 2 diabetes mellitus and prognosis in early stage breast cancer women. Med Oncol. 2012;29:1576–80. doi: 10.1007/s12032-011-0109-4. - DOI - PubMed
    1. Redaniel MT, Jeffreys M, May MT, Ben-Shlomo Y, Martin RM. Associations of type 2 diabetes and diabetes treatment with breast cancer risk and mortality: a population-based cohort study among British women. Cancer Causes Control. 2012;23:1785–95. doi: 10.1007/s10552-012-0057-0. - DOI - PubMed
    1. Carmichael AR. Obesity and prognosis of breast cancer. Obes Rev. 2006;7:333–40. doi: 10.1111/j.1467-789X.2006.00261.x. - DOI - PubMed

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