Diabetes, Metformin, and Breast Cancer in Postmenopausal Women

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J Clin Oncol. 2012 Jun 11;[Epub Ahead of Print], RT Chlebowski, A McTiernan, J Wactawski-Wende, JE Manson, AK Aragaki, T Rohan, E Ipp, VG Kaklamani, M Vitolins, R Wallace, M Gunter, LS Phillips, H Strickler, K Margolis, DM Euhus

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The use of metformin in postmenopausal women with diabetes has been shown to have a protective effect against the occurrence of invasive breast cancer.

SUMMARY

OncologySTAT Editorial Team


Diabetes has been linked to adverse outcomes in patients with breast cancer. According to an analysis by Chlebowski and colleagues, women with diabetes who receive metformin have a lower incidence of breast cancer than women who take other antidiabetic medications The investigators noted that previous studies and meta-analyses found that patients with breast cancer and diabetes had significantly higher all-cause mortality than did those without diabetes. In addition, they noted that all patients with breast cancer with higher fasting levels of insulin, higher levels of C-peptide, or increased insulin resistance are at increased risk of breast cancer mortality.

In total, the investigators evaluated 68,019 postmenopausal women, including 3,407 with diabetes, who participated in the Women’s Health Initiative (WHI) clinical trials. The WHI program included four clinical trials and an observational study. General eligibility required patients to be between 50 and 79 years of age, to be accessible for follow-up, and to have an estimated survival of 3 or more years. Subgroup comparisons involved age, body mass index, physical activity, alcohol use, use of estrogen alone, use of estrogen plus progestin, and time of diagnosis of diabetes.

It should be noted that women with diabetes who used metformin were similar to women who used other antidiabetic medications, except they were somewhat less likely to be black, to never have smoked, and to be older. In addition, they were less likely to be using sulfonylureas and were not using insulin. The investigators noted that the percentage of women with diabetes who used metformin increased year by year from 20.3% at baseline to 30.6%, 41.0%, 51.6%, and 55.0% in years 1, 3, 6, and 9, respectively.

Although there was no difference in the incidence of invasive breast cancer (hazard ratio [HR], 0.99; 95% CI, 0.85–1.14) between all women with diabetes and women without diabetes, when women with diabetes were compared with women without diabetes, the incidence of invasive breast cancer was associated with the type of diabetes medication (P = .04). Indeed, the incidence of breast cancer was lower in women with diabetes who received metformin (HR, 0.75; 95% CI, 0.57–0.99) than in women with diabetes who used other medications (HR, 1.16; 95% CI, 0.93–1.45). Women who received metformin were associated with more HER2-positive cancers. In addition, in women receiving metformin, the number of localized cancers was substantially lower than that in women not receiving metformin (65 vs 90 cases).

In closing, the investigators noted that their findings were of most direct relevance to women with diabetes, especially those who were overweight or obese. Even though their findings were associated with a subset of women with diabetes, the totality of available evidence does provide support for the ongoing clinical studies of metformin, including a prospective, full-scale, multicenter adjuvant trial and proof-of-principle studies in prevention settings.

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