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Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 528
© 2008 American Society of Clinical Oncology
The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST)
S. Jiralerspong,
S. H. Giordano,
F. Meric-Bernstam,
C. M. Barnett,
S. Kau,
M. C. Hung,
G. N. Hortobagyi and
A. M. Gonzalez-Angulo
University of Texas M. D. Anderson Cancer Center, Houston, TX
528
Background: Recent epidemiologic studies suggest that metformin use in diabetic patients decreases cancer incidence and cancer-related mortality. Metformin inhibits the growth of breast cancer cell lines by activating AMP kinase and thereby inhibiting the mTOR pathway/protein translation. We hypothesized that the antiproliferative effects of metformin might increase the efficacy of NST in diabetic BC patients. Methods: From the M.D. Anderson Breast Medical Oncology database, we identified 2,529 patients that received NST for early- stage BC. Patients’ characteristics were compared by groups: non-diabetic (ND), diabetics taking metformin (DM) during NST, and diabetics not taking metformin (DN) during NST. pCR was defined as no residual disease in breast and nodes. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier product. Results: There were 2,374 (94%) ND, 68 (2.7%) DM, and 87 (3.4%) DN patients. Median age was 49 (range 21–87). 1,513 (60%) were stage I-II; 1,004 (40%) were stage III. 64% of tumors were hormone- receptor (HR) and 25% were HER2-positive. Prognostic factors were balanced overall in the 3 groups, though ND patients were more frequently white and pre-menopausal. pCR was seen in 16% ND, 24% DM, and 8% DN patients (p=0.03). At a median follow-up of 39 months, there have been 622 recurrences and 500 deaths. RFS was not statistically different between the three groups (p=0.84). The 3-year OS was significantly better in the ND (85.9%) group compared to the DM (80.9%) and DN (77.6%) groups (p=0.02). After adjustment for stage, grade, HR and HER2 status, ethnicity, and menopausal status, the odds ratio for achieving pCR was 1.32 (95% CI=0.69, 2.51; p=0.08) for DM and 0.45 (95%CI = 0.20, 1.02; p=0.03) for DN, as compared to ND patients. We are currently expanding our analysis cohorts. Conclusions: Diabetic BC patients receiving NST and metformin have higher pCR rates than those not receiving metformin. As metformin has a novel mechanism of action, further studies to evaluate its potential as an antitumor agent are warranted.
No significant financial relationships to disclose.
Abstract presentation from the 2008 ASCO Annual Meeting
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