Metformin is distributed to tumor tissue in breast cancer patients in vivo: A 11C-metformin PET/CT study.

PURPOSE: Epidemiological studies and randomized clinical trials suggest that the antidiabetic drug, metformin, may have anti-neoplastic effects. The mechanism that mediates these beneficial effects has been suggested to involve direct action on cancer cells, but this will require distribution of metformin in tumor tissue. The present study was designed to investigate metformin distribution in vivo in breast and liver tissue in breast cancer patients. METHODS: Seven patients recently diagnosed with ductal carcinoma were recruited. Using PET/CT, tissue distribution of metformin was determined in vivo for 90 min after injection of a carbon-11-labeled metformin tracer. After surgery, tumor tissue was investigated for gene expression levels of metformin transporter proteins. RESULTS: Tumor tissue displayed a distinct uptake of metformin compared to normal breast tissue AUC0-90 min (75.4 ± 5.5 vs 42.3 ± 6.3) g/ml*min (p = 0.01). Maximal concentration in tumor was at 1 min where it reached approximately 30% of the activity in the liver. The metformin transporter protein with the highest gene expression in tumor tissue was multidrug and toxin extrusion 1 (MATE 1) followed by plasma membrane monoamine transporter (PMAT). CONCLUSION: This study confirms that metformin is transported into tumor tissue in women with breast cancer. This finding support that metformin may have direct anti-neoplastic effects on tumor cells in breast cancer patients. However, distribution of metformin in tumor tissue is markedly lower than in liver, an established metformin target tissue.

Recurrence pattern and prognosis in low-risk breast cancer patients--data from the DBCG 89-A programme.

The invasive disease free survival, the overall survival, and the relative risk of death compared to the Danish population as well as the risk of recurrence and new malignancies is reported for low-risk breast cancer patients of the DBCG 89-A programme. The study includes a comparison between those patients who, according to the present criteria, would be defined low-risk and those who would be defined high-risk (the retrospective lowhigh-risk group) and a comparison of treatment by mastectomy and BCS combined with radiation therapy. The DBCG 89-A programme scheduled 10 years of follow-up. Data was supplemented by record linkage to the Hospital Discharge Registry (date of event) and the Central Population Registry (date of death). The study population consisted of 8 850 patients. With 12 years of follow-up 3 811 events (43%) were recorded: loco-regional recurrence 8%, distant recurrence 11%, contralateral cancer 6%, secondary cancer 8%, and deaths 11%. The DBCG registry had an incomplete reporting of events in these low-risk patients, due to premature discontinuation of control. The incidence of recurrences was higher for the retrospective low --> high-risk group than for the low-risk group. The 10-year overall survival was 76%; lower in the retrospective low --> high-risk group (71%) than in the low-risk group (83%). The 5-year survival following local recurrence was 68% after mastectomy and 81% after BCS. The risk of mortality was higher than in the general population for all subgroups of patients. The relative risk of mortality expressed in terms of the standardized mortality ratio was 10.4 for young patients (26-39 years) and 1.2 for old patients aged 70-74 years and 1.3 for patients in the retrospective low-risk group and 1.9 for patients in the low --> high-risk group. The loco-regional treatment given did not cure all patients, in particular young patients and those of the retrospective low --> high-risk group.