Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial

Purpose: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). Methods: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). Results: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. Conclusions: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted

Whither the PET Scan? The Role of PET Imaging in the Staging and Treatment of Breast Cancer

Metabolic imaging may contribute to a better knowledge of the biology of breast cancer and to new drugs development. Positron emission tomography (PET) with the radiolabeled glucose analogue 2- [18F]-fluorodeoxyglucose (18F-FDG) allows quantitative assessment of glucose utilization in tumor tissue. This technique utilizes a class of radioisotopes that decay by emitting a positron. The positron travels a short distance (1 mm) before interacting with an electron in what is called an annihilation reaction. This results in the creation of two high-energy photons that are emitted in opposite directions. The PET scanner detects such annihilation radiations and produces a three-dimensional picture of the distribution of the radiolabeled tracer. 18F-FDG PET has currently a limited role in breast cancer, due to its low sensitivity that makes it not recommended in most of the cases, especially in early disease. Potentially, the most useful application of PET/CT is monitoring the changes in 18F-FDG uptake during chemotherapy in order to detect an early response to treatment. In fact, while morphological changes due to effective chemotherapy are not detectable until late in the course of treatment, metabolic changes generally occur earlier. In this paper, we summarize the current and future applications of PET in the management of breast cancer