In an analysis from the Canadian Cancer Trials Group MA.32 study reported in the Journal of Clinical Oncology, Pamela Goodwin, MD, MSc, FRCPC, FASCO, and colleagues found that adjuvant metformin did not reduce the risk of new primary invasive cancers vs placebo in patients with early breast cancer. Prior analyses from the trial showed no benefit of metformin in invasive disease–free or overall survival.
Study Details
In the international double-blind phase III trial, 3,649 patients (younger than age 75) without diabetes who had high-risk T1–3, N0–3, M0 breast cancer were randomly assigned between 2010 and 2013 to receive metformin at 850 mg twice daily (n = 1,824) or placebo (n = 1,825) for 5 years. The outcome measure in the current analysis was development of new primary invasive cancers (outside the ipsilateral breast) as a first invasive disease–free survival event.
Metformin did not reduce the risk of new cancer development in these nondiabetic patients with breast cancer.— Pamela Goodwin, MD, MSc, FRCPC, FASCO, and colleagues
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Key Findings
Median follow-up was 95.9 months (range = 0–121 months). New primary cancers as a first invasive disease–free survival event were reported in 102 patients in the metformin group vs 82 in the placebo group (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 0.94–1.68, P = .13). Contralateral invasive breast cancer occurred in 27 vs 21 patients (HR = 1.29, 95% CI = 0.72–2.27, P = .40). Nonbreast invasive cancers occurred in 75 vs 61 patients (HR = 1.24, 95% CI = 0.88–1.74); the most common nonbreast invasive cancers were gynecologic (n = 31), lung (n = 26), hematologic (n = 23), gastrointestinal (n = 17), and melanoma (n = 13).
No significant benefit of metformin in reducing risk was observed among patients with hormone receptor–positive disease (HR = 1.19, 95% CI = 0.83–1.69) or hormone receptor–negative disease (HR = 1.44, 95% CI = 0.86–2.41; P = .53 for interaction) or among those with HER2-positive disease (HR = 0.83, 95% CI = 0.39–1.81) or HER2-negative disease (HR = 1.36, 95% CI = 0.99–1.86; P = .25 for interaction). No differences in risk were observed based on receipt of adjuvant hormonal therapy, with hazard ratios of 1.23 (95% CI = 0.73–2.08) for tamoxifen, 1.34 (95% CI = 0.80–2.24) for aromatase inhibitors, and 1.21 (95% CI = 0.75–1.95) for none (P = .96 for interaction).
The investigators concluded: “Metformin did not reduce the risk of new cancer development in these nondiabetic patients with breast cancer.”
Dr. Goodwin, of Mount Sinai Hospital, Toronto, and University of Toronto, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Canadian Cancer Society Research Institute, U.S. National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.
