Metformin does not improve outcomes in patients with early-stage breast cancer

The phase 3 CCTGMA.32 trial showed no benefit of metformin in both patients with hormone receptor (HR)-positive and HR-negative moderate/high risk, early-stage breast cancer.

Clinical and epidemiologic evidence has linked hyperinsulinemia, insulin resistance, obesity, and diabetes to poor breast cancer outcomes. Metformin is an inexpensive, widely available, and well-tolerated drug that promotes modest weight loss and lowers insulin. In addition, metformin is a potential anti-cancer agent; indirectly by lowering the circulating insulin levels and directly by activating adenosine monophosphate-activated protein kinase (AMPK) [1]. CCTGMA.32 (NCT01101438) is a phase 3, randomised, double-blind, placebo-controlled adjuvant trial of metformin versus placebo in early-stage breast cancer. Dr Pamela Goodwin (Lunenfeld-Tanenbaum Research Institute, Canada) presented the results [2].

After standard therapy, 3,649 non-diabetic patients were randomised to metformin (850 mg twice daily, 5 years) or placebo. After the second interim analysis (median follow-up of 29.5 months), intervention was stopped for patients who were HR-negative (n=1,116). In HR-positive patients, the incidence of both invasive disease-free survival (IDSF) events and overall survival (OS) events were evenly distributed between both treatment arms at 96 months of follow-up (IDSF: HR 1.01; 95% CI 0.84–1.21; P=0.93; OS: HR 1.10; 95% CI 0.86–1.41; P=0.47).

“Therefore, metformin should not be used as an adjuvant breast cancer treatment in this population,” concluded Dr Goodwin. “Of note, this recommendation should not be extrapolated to the use of metformin to treat diabetes in breast cancer patients.”

1. Goodwin PJ, et al. Clin Oncol. 2009;27:3271–3273.
2. Goodwin PJ, et al. CCTGMA.32, a phase III randomized double-blind placebo controlled adjuvant trial of metformin (MET) vs placebo (PLAC) in early breast cancer (BC): Results of the primary efficacy analysis (clinical trials.gov NCT01101438). GS1-08, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022