Breast Cancer Coverage from Every Angle

Reducing Levels of CA 15-3 With Metformin in Patients With Early-Stage Breast Cancer

By: Hope Craig, MSPH
Posted: Tuesday, October 26, 2021

Published in the journal JNCI Cancer Spectrum, a phase III randomized trial in early-stage breast cancer examined the effects of the diabetes drug metformin versus placebo on circulating levels of cancer antigen (CA) 15-3—a tumor marker and regulator of cellular metabolism. Conducted by Vuk Stambolic, PhD, and colleagues at the University of Toronto, the study was a part of the Canadian Cancer Trials Group MA.32 trial, which was conducted in North America, the United Kingdom, and Switzerland.

“Our observation that metformin reduces CA 15-3 by approximately 6% was corroborated in a large placebo-controlled randomized trial,” the authors concluded. The clinical implications of these findings will be explored in further analyses of these trial data.

The study included 3,649 women with T1–3, N0–3, M0 breast cancer. A total of 1,824 received metformin, and 1,825 received placebo. The CA 15-3 population ultimately included 1,307 metformin recipients and 1,401 placebo recipients. Fasting plasma samples before treatment and 6 months on treatment were centrally assayed for CA 15-3. The researchers also analyzed genomic DNA for the rs11212617 single-nucleotide polymorphism (SNP). This SNP population included 1,301 metformin recipients and 1,392 placebo recipients.

The mean age of participants was 52.4 years old. The majority had T2 or T3, node-positive, hormone receptor–positive, HER2-negative breast cancer and were treated with (neo)adjuvant chemotherapy and hormone therapy. At baseline, the mean baseline CA 15-3 level was 17.7 U/mL with metformin and 18.0 U/mL without. At 6 months of follow-up, the CA 15-3 level was statistically significantly reduced in metformin versus placebo arms (absolute geometric mean reduction in CA 15-3 level = 7.7% vs. 2.0%, P < .001), independent of tumor characteristics and treatment characteristics, as well as SNP status.

Disclosures: Full authors’ disclosures are available at

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