Table 3.
Association between metformin use and breast cancer, The Sister Study
| Total breast cancer | ER+ breast cancer | ER− breast cancer | TNBC | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of cases | Age-adjusted HR (95% CI) * | Multivariable-adjusted HR (95% CI) † | No. of cases | Multivariable-adjusted HR (95% CI) † | No. of cases | Multivariable-adjusted HR (95% CI) † | No. of cases | Multivariable-adjusted HR (95% CI) † | ||
| Antidiabetic medication use | No T2D | 2401 | 1 (reference) | 1 (reference) | 1800 | 1 (reference) | 303 | 1 (reference) | 155 | 1 (reference) |
| No medication | 70 | 1.07 (0.84-1.35) | 1.02 (0.81-1.30) | 46 | 0.93 (0.70-1.25) | 6 | 0.74 (0.33-1.66) | 3 | NA | |
| Other medication‡ | 30 | 0.96 (0.67-1.38) | 0.95 (0.66-1.37) | 27 | 1.20 (0.82-1.76) | 3 | NA | 2 | NA | |
| Metformin | 177 | 1.02 (0.87-1.19) | 0.98 (0.83-1.15) | 111 | 0.86 (0.70-1.05) | 27 | 1.25 (0.84-1.88) | 20 | 1.74 (1.06-2.83) | |
| Duration of Metformin use (y) | No T2D | 2401 | 1 (reference) | 1 (reference) | 1800 | 1 (reference) | 303 | 1 (reference) | 155 | 1 (reference) |
| No Metformin use | 100 | 1.03 (0.85-1.26) | 1.00 (0.82-1.23) | 73 | 1.01 (0.80-1.28) | 9 | 0.75 (0.39-1.47) | 5 | 0.80 (0.33-1.93) | |
| < 2 | 33 | 0.94 (0.67-1.33) | 0.91 (0.64-1.29) | 26 | 0.96 (0.65-1.42) | 14 | 1.35 (0.78-2.32) | 10 | 1.83 (0.95-3.50) | |
| 2 to <5 | 43 | 0.99 (0.73-1.34) | 0.95 (0.70-1.29) | 27 | 0.82 (0.56-1.21) | |||||
| 5 to <10 | 70 | 1.19 (0.94-1.51) | 1.14 (0.90-1.46) | 42 | 0.96 (0.70-1.32) | 13 | 1.16 (0.66-2.05) | 10 | 1.65 (0.85-3.21) | |
| ≥ 10 | 31 | 0.85 (0.60-1.21) | 0.81 (0.57-1.16) | 16 | 0.62 (0.38-1.01) | |||||
| P trend | 0.79 | 0.81 | 0.09 | 0.44 | 0.05 | |||||
Abbreviations: T2D, type 2 diabetes; ER, estrogen receptor; HR, hazard ratio; 95% CI, 95% confidence interval; +, positive; −, negative; TNBC, triple-negative breast cancer.
Adjusted for age (age as the primary time scale)
Adjusted for race/ethnicity (non-Hispanic white, non-Hispanic black, or other), educational attainment (high school degree or less, some college, college degree or higher), height, body mass index (BMI) at 30-39 years old (<18.5, 18.5 to <25, 25 to <30, 30 to <35, 35 to <40, or ≥40 kg/m2), physical activity (metabolic equivalent hours/week), recent mammogram screening (<1 y, 1 to 2y, >2y), age at menarche ≤11 years old, number of relatives diagnosed with breast cancer (1, ≥2), and birth cohort (born in <1945, 1945 to <1955, 1955 to <1965 or ≥1965), as well as time varying covariates including BMI, menopausal status (binary), interaction term between BMI and menopausal status, age at menopause, alcohol consumption (never drinker, former drinker, current drinker <1 drink/day, current drinker 1-1.9 drinks/day, current drinker ≥2 drinks/day), smoking status (≥20 pack-years, <20 and ≥10 pack-years, <10 and >0 pack-years, never smoker), use of any hormonal birth control (never, ever), hormone therapy (none, estrogen only, both estrogen and progesterone), age at first childbirth (nulliparous, <21 years, 21 to <25 years, 25 to <29 years, or ≥29 years), lifetime duration of breastfeeding (weeks, none and tertiles among women with any breastfeeding), and parity (0, 1, 2, ≥3 births).
Sulfonylureas, thiazolidinediones, DPP-4 inhibitors, insulin, and others.