Table 2.
Multivariable1 adjusted effects of Diabetes Treatment (Metformin or other diabetic medication vs. non-diabetic) on Invasive Cancer Types and Cancer death by Duration in the Women’s Health Initiative CT
| Main effect Duration (years) | Non-diabetic | Metformin use | Other diabetic medication use | p-diff3 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | % | N | % | HR | (95% CI) | p2 | N | % | HR | (95% CI) | p2 | ||
| Total invasive cancer | 7,335 | (1.11) | 405 | (1.38) | 1.11 | (0.99, 1.24) | 342 | (1.38) | 1.13 | (1.00, 1.27) | |||
| <3.5 | 225 | (1.43) | 1.17 | (1.01, 1.35) | 0.27 | 136 | (1.16) | 1.04 | (0.87, 1.24) | 0.58 | 0.24 | ||
| 3.5–≤5 | 68 | (1.33) | 1.09 | (0.84, 1.40) | 74 | (1.71) | 1.41 | (1.10, 1.80) | |||||
| >5 | 112 | (1.32) | 1.02 | (0.83, 1.25) | 132 | (1.51) | 1.11 | (0.91, 1.34) | |||||
| Bone, connective tissue and skin | 3,194 | (0.47) | 159 | (0.52) | 1.00 | (0.84, 1.20) | 131 | (0.51) | 1.11 | (0.92, 1.34) | |||
| <3.5 | 94 | (0.58) | 1.14 | (0.91, 1.43) | 0.05 | 57 | (0.47) | 1.03 | (0.77, 1.36) | 0.94 | 0.17 | ||
| 3.5–≤5 | 25 | (0.47) | 1.00 | (0.67, 1.51) | 29 | (0.65) | 1.56 | (1.08, 2.26) | |||||
| >5 | 40 | (0.45) | 0.74 | (0.52, 1.07) | 45 | (0.49) | 0.99 | (0.72, 1.36) | |||||
| Invasive breast cancer | 2,839 | (0.42) | 146 | (0.48) | 1.01 | (0.84, 1.22) | 120 | (0.47) | 1.14 | (0.93, 1.38) | |||
| <3.5 | 88 | (0.54) | 1.18 | (0.94, 1.49) | 0.04 | 52 | (0.43) | 1.06 | (0.79, 1.42) | 0.79 | 0.20 | ||
| 3.5–≤5 | 21 | (0.39) | 0.93 | (0.59, 1.44) | 28 | (0.63) | 1.67 | (1.14, 2.43) | |||||
| >5 | 37 | (0.42) | 0.76 | (0.52, 1.11) | 40 | (0.44) | 0.98 | (0.70, 1.37) | |||||
| Lip, oral cavity and pharynx | 83 | (0.01) | 3 | (0.01) | 0.74 | (0.22, 2.42) | 4 | (0.02) | 1.35 | (0.48, 3.80) | |||
| <3.5 | 1 | (0.01) | 2 | (0.02) | |||||||||
| 3.5–≤5 | 0 | (0.00) | 0 | (0.00) | |||||||||
| >5 | 2 | (0.02) | 2 | (0.02) | |||||||||
| Digestive organs and peritoneum | 1,345 | (0.19) | 94 | (0.30) | 1.30 | (1.03, 1.64) | 97 | (0.37) | 1.49 | (1.18, 1.87) | |||
| <3.5 | 54 | (0.32) | 1.41 | (1.05, 1.91) | 0.31 | 34 | (0.28) | 1.23 | (0.85, 1.76) | 0.22 | 0.11 | ||
| 3.5–≤5 | 18 | (0.32) | 1.35 | (0.81, 2.27) | 21 | (0.46) | 1.76 | (1.09, 2.86) | |||||
| >5 | 22 | (0.24) | 1.07 | (0.69, 1.67) | 42 | (0.45) | 1.66 | (1.19, 2.33) | |||||
| Respiratory and intrathoracic organs | 860 | (0.12) | 52 | (0.16) | 1.24 | (0.91, 1.70) | 36 | (0.14) | 0.83 | (0.56, 1.24) | |||
| <3.5 | 30 | (0.18) | 1.44 | (0.96, 2.14) | 0.35 | 16 | (0.13) | 1.03 | (0.61, 1.77) | 0.42 | 0.96 | ||
| 3.5–≤5 | 8 | (0.14) | 1.02 | (0.48, 2.17) | 5 | (0.11) | 0.52 | (0.17, 1.61) | |||||
| >5 | 14 | (0.15) | 1.06 | (0.59, 1.89) | 15 | (0.16) | 0.75 | (0.39, 1.46) | |||||
| Reproductive tract | 828 | (0.12) | 40 | (0.13) | 1.10 | (0.79, 1.54) | 39 | (0.15) | 1.26 | (0.88, 1.80) | |||
| <3.5 | 20 | (0.12) | 1.09 | (0.69, 1.71) | 0.95 | 13 | (0.11) | 0.98 | (0.55, 1.74) | 0.28 | 0.46 | ||
| 3.5–≤5 | 7 | (0.13) | 1.15 | (0.54, 2.43) | 9 | (0.20) | 1.51 | (0.71, 3.20) | |||||
| >5 | 13 | (0.14) | 1.11 | (0.62, 1.98) | 17 | (0.18) | 1.49 | (0.87, 2.56) | |||||
| Urinary organs | 293 | (0.04) | 25 | (0.08) | 1.45 | (0.92, 2.28) | 14 | (0.05) | 1.06 | (0.60, 1.87) | |||
| <3.5 | 5 | (0.03) | 0.55 | (0.20, 1.48) | <0.001 | 6 | (0.05) | 1.19 | (0.52, 2.69) | 0.38 | 0.004 | ||
| 3.5–≤5 | 4 | (0.07) | 1.07 | (0.34, 3.38) | 4 | (0.09) | 1.77 | (0.65, 4.79) | |||||
| >5 | 16 | (0.17) | 3.04 | (1.76, 5.25) | 4 | (0.04) | 0.61 | (0.19, 1.92) | |||||
| Malignant Neoplasm of L/H4 Tissue | 769 | (0.11) | 35 | (0.11) | 0.87 | (0.60, 1.27) | 37 | (0.14) | 1.24 | (0.88, 1.75) | |||
| <3.5 | 20 | (0.12) | 0.96 | (0.59, 1.56) | 0.44 | 13 | (0.11) | 1.04 | (0.60, 1.82) | 0.61 | 0.36 | ||
| 3.5–≤5 | 7 | (0.13) | 0.97 | (0.43, 2.17) | 9 | (0.20) | 1.64 | (0.81, 3.32) | |||||
| >5 | 8 | (0.09) | 0.67 | (0.31, 1.41) | 15 | (0.16) | 1.27 | (0.76, 2.15) | |||||
| Other and Unknown | 407 | (0.06) | 26 | (0.08) | 1.19 | (0.77, 1.85) | 15 | (0.06) | 0.82 | (0.47, 1.44) | |||
| <3.5 | 14 | (0.08) | 1.20 | (0.67, 2.16) | 0.98 | 5 | (0.04) | 0.71 | (0.29, 1.72) | 0.54 | 0.64 | ||
| 3.5–≤5 | 4 | (0.07) | 1.12 | (0.41, 3.03) | 3 | (0.07) | 0.71 | (0.17, 2.85) | |||||
| >5 | 8 | (0.09) | 1.23 | (0.57, 2.64) | 7 | (0.07) | 1.02 | (0.45, 2.31) | |||||
| Cancer death | 1,854 | (0.26) | 102 | (0.32) | 1.00 | (0.80, 1.25) | 124 | (0.47) | 1.46 | (1.20, 1.78) | |||
| <3.5 | 49 | (0.29) | 1.01 | (0.74, 1.37) | 0.92 | 40 | (0.32) | 1.21 | (0.87, 1.69) | 0.17 | 0.41 | ||
| 3.5–≤5 | 19 | (0.34) | 0.93 | (0.57, 1.51) | 24 | (0.52) | 1.59 | (1.05, 2.41) | |||||
| >5 | 34 | (0.37) | 1.04 | (0.72, 1.51) | 60 | (0.63) | 1.64 | (1.24, 2.17) | |||||
| Cancer death (incident only) | 1,854 | (0.26) | 45 | (0.26) | 0.82 | (0.59, 1.14) | 51 | (0.54) | 1.57 | (1.17, 2.11) | |||
| <3.5 | 28 | (0.27) | 0.98 | (0.65, 1.47) | 0.07 | 24 | (0.40) | 1.30 | (0.85, 1.98) | <0.001 | <0.001 | ||
| 3.5–≤5 | 8 | (0.25) | 0.67 | (0.32, 1.41) | 9 | (0.52) | 1.39 | (0.72, 2.70) | |||||
| >5 | 9 | (0.25) | 0.60 | (0.27, 1.34) | 18 | (0.99) | 2.47 | (1.50, 4.07) | |||||
The Cox proportional hazard analyses were adjusted for the baseline covariates of age, race/ethnicity, education, smoking, physical activity, aspirin use, history of hyperlipidemia, duration of HT use, BMI and WHR; baseline hazard functions were allowed to vary by age (10-year group), study participation (four hormone therapy trial randomization arms, the dietary trial randomization arms, or enrollment into the OS), hysterectomy status and enrollment in WHI extensions (I/II; time-dependent).
p-value corresponds to a test of trend for duration of metformin use or other known diabetic medication.
p-value corresponds to test of whether trend for duration of metformin use differs from trend of other known medication use.
lymphatic and Hematopoietic.