Recent oral contraceptive use by monophasic and triphasic formulations and invasive breast cancer risk by all cases (left) and ER+ cases (right)
| . | Controls (n = 21,952) . | All cases (n = 1,102) . | . | Controls (n = 14,704) . | ER+ cases (n = 738) . | . |
|---|---|---|---|---|---|---|
| OC formulationa . | n (%) . | n (%) . | OR (95% CI)b . | n (%) . | n (%) . | OR (95% CI)b . |
| Never/former use | 19,953 (90.9) | 957 (86.8) | Reference | 13,394 (91.1) | 637 (86.3) | Reference |
| Monophasic OCs | ||||||
| Any monophasic OC | 1,614 (7.4) | 114 (10.3) | 1.5 (1.2–1.9) | 1,068 (7.3) | 79 (10.7) | 1.6 (1.2–2.0) |
| By estrogen dose and progestin type and dose | ||||||
| Low estrogen dose | ||||||
| Norethindrone acetate | ||||||
| 1.00 mg | 328 (1.5) | 17 (1.5) | 1.1 (0.7–1.8) | 228 (1.6) | 13 (1.8) | 1.2 (0.7–2.1) |
| Moderate estrogen dose | 1,259 (5.7) | 95 (8.6) | 1.6 (1.3–2.0) | 816 (5.6) | 64 (8.7) | 1.7 (1.3–2.2) |
| Any norethindrone | 616 (2.8) | 40 (3.6) | 1.4 (1.0–1.9) | 398 (2.7) | 22 (3.0) | 1.2 (0.8–1.9) |
| 0.50 mg | 229 (1.0) | 9 (0.8) | 0.8 (0.4–1.6) | 148 (1.0) | 5 (0.7) | 0.7 (0.3–1.8) |
| 1.00 mg | 358 (1.6) | 27 (2.5) | 1.6 (1.1–2.4) | 230 (1.6) | 13 (1.8) | 1.2 (0.7–2.2) |
| 1.00 mgc | 46 (0.2) | 5 (0.5) | 2.3 (0.9–5.9) | 26 (0.2) | 5 (0.7) | 4.2 (1.6–11.1) |
| Norethindrone acetate | ||||||
| 1.50 mg | 300 (1.4) | 30 (2.7) | 2.1 (1.4–3.1) | 205 (1.4) | 24 (3.3) | 2.5 (1.6–3.9) |
| Ethynodiol diacetate | ||||||
| 1.00 mg | 86 (0.4) | 11 (1.0) | 2.8 (1.5–5.2) | 55 (0.4) | 8 (1.1) | 3.2 (1.5–6.7) |
| Levonorgestrel | ||||||
| 0.15 mg | 166 (0.8) | 10 (0.9) | 1.3 (0.7–2.5) | 104 (0.7) | 5 (0.7) | 1.0 (0.4–2.6) |
| Norgestimate | ||||||
| 0.25 mg | 96 (0.4) | 6 (0.5) | 1.4 (0.6–3.2) | 67 (0.5) | 5 (0.7) | 1.7 (0.7–4.2) |
| Triphasic OCs | ||||||
| Any triphasic OC | 456 (2.1) | 37 (3.4) | 1.8 (1.2–2.5) | 283 (1.9) | 25 (3.4) | 1.9 (1.3–3.0) |
| By progestin type and dosed | ||||||
| Moderate estrogen dose | ||||||
| Norethindrone | ||||||
| 0.71 mg | 97 (0.4) | 8 (0.7) | 1.8 (0.9–3.7) | 54 (0.4) | 6 (0.8) | 2.4 (1.0–5.7) |
| 0.75 mg | 132 (0.6) | 19 (1.7) | 3.1 (1.9–5.1)e | 76 (0.5) | 12 (1.6) | 3.5 (1.9–6.4) |
| Levonorgestrel | ||||||
| 0.09 mg | 153 (0.7) | 13 (1.2) | 1.8 (1.0–3.3) | 94 (0.6) | 9 (1.2) | 2.1 (1.0–4.2) |
| Norgestimate | ||||||
| 0.22 mg | 96 (0.4) | 5 (0.5) | 1.1 (0.5–2.8) | 67 (0.5) | 4 (0.5) | 1.3 (0.5–3.7) |
| . | Controls (n = 21,952) . | All cases (n = 1,102) . | . | Controls (n = 14,704) . | ER+ cases (n = 738) . | . |
|---|---|---|---|---|---|---|
| OC formulationa . | n (%) . | n (%) . | OR (95% CI)b . | n (%) . | n (%) . | OR (95% CI)b . |
| Never/former use | 19,953 (90.9) | 957 (86.8) | Reference | 13,394 (91.1) | 637 (86.3) | Reference |
| Monophasic OCs | ||||||
| Any monophasic OC | 1,614 (7.4) | 114 (10.3) | 1.5 (1.2–1.9) | 1,068 (7.3) | 79 (10.7) | 1.6 (1.2–2.0) |
| By estrogen dose and progestin type and dose | ||||||
| Low estrogen dose | ||||||
| Norethindrone acetate | ||||||
| 1.00 mg | 328 (1.5) | 17 (1.5) | 1.1 (0.7–1.8) | 228 (1.6) | 13 (1.8) | 1.2 (0.7–2.1) |
| Moderate estrogen dose | 1,259 (5.7) | 95 (8.6) | 1.6 (1.3–2.0) | 816 (5.6) | 64 (8.7) | 1.7 (1.3–2.2) |
| Any norethindrone | 616 (2.8) | 40 (3.6) | 1.4 (1.0–1.9) | 398 (2.7) | 22 (3.0) | 1.2 (0.8–1.9) |
| 0.50 mg | 229 (1.0) | 9 (0.8) | 0.8 (0.4–1.6) | 148 (1.0) | 5 (0.7) | 0.7 (0.3–1.8) |
| 1.00 mg | 358 (1.6) | 27 (2.5) | 1.6 (1.1–2.4) | 230 (1.6) | 13 (1.8) | 1.2 (0.7–2.2) |
| 1.00 mgc | 46 (0.2) | 5 (0.5) | 2.3 (0.9–5.9) | 26 (0.2) | 5 (0.7) | 4.2 (1.6–11.1) |
| Norethindrone acetate | ||||||
| 1.50 mg | 300 (1.4) | 30 (2.7) | 2.1 (1.4–3.1) | 205 (1.4) | 24 (3.3) | 2.5 (1.6–3.9) |
| Ethynodiol diacetate | ||||||
| 1.00 mg | 86 (0.4) | 11 (1.0) | 2.8 (1.5–5.2) | 55 (0.4) | 8 (1.1) | 3.2 (1.5–6.7) |
| Levonorgestrel | ||||||
| 0.15 mg | 166 (0.8) | 10 (0.9) | 1.3 (0.7–2.5) | 104 (0.7) | 5 (0.7) | 1.0 (0.4–2.6) |
| Norgestimate | ||||||
| 0.25 mg | 96 (0.4) | 6 (0.5) | 1.4 (0.6–3.2) | 67 (0.5) | 5 (0.7) | 1.7 (0.7–4.2) |
| Triphasic OCs | ||||||
| Any triphasic OC | 456 (2.1) | 37 (3.4) | 1.8 (1.2–2.5) | 283 (1.9) | 25 (3.4) | 1.9 (1.3–3.0) |
| By progestin type and dosed | ||||||
| Moderate estrogen dose | ||||||
| Norethindrone | ||||||
| 0.71 mg | 97 (0.4) | 8 (0.7) | 1.8 (0.9–3.7) | 54 (0.4) | 6 (0.8) | 2.4 (1.0–5.7) |
| 0.75 mg | 132 (0.6) | 19 (1.7) | 3.1 (1.9–5.1)e | 76 (0.5) | 12 (1.6) | 3.5 (1.9–6.4) |
| Levonorgestrel | ||||||
| 0.09 mg | 153 (0.7) | 13 (1.2) | 1.8 (1.0–3.3) | 94 (0.6) | 9 (1.2) | 2.1 (1.0–4.2) |
| Norgestimate | ||||||
| 0.22 mg | 96 (0.4) | 5 (0.5) | 1.1 (0.5–2.8) | 67 (0.5) | 4 (0.5) | 1.3 (0.5–3.7) |
Abbreviation: OC, oral contraceptive.
aRecent use is defined as filling at least one combined oral contraceptive script in the year before reference date. Categories are not mutually exclusive and numbers may not add up to column totals because of missing values. Oral contraceptive formulations with <5 controls or invasive cases as recent users are not displayed. Low estrogen dose = 20 μg ethinyl estradiol and moderate estrogen dose = 30–35 μg ethinyl estradiol or 50 μg mestranol.
bAll ORs are implicitly adjusted for the matching factors.
cContains the estrogen mestranol rather than ethinyl estradiol.
dAll triphasic formulations contain moderate estrogen dose. Average progestin doses are listed. The dosing schedules are as follows: (i) Norethindrone 0.71 mg = 35 μg ethinyl estradiol/0.5 mg (7 days), 1.0 mg (9 days), 0.5 mg (5 days) norethindrone; (ii) norethindrone 0.75 mg = 35 μg ethinyl estradiol/0.5 mg (7 days), 0.75 mg (7 days), 1.0 mg (7 days) norethindrone; (iii) levonorgestrel 0.09 mg = 30 μg ethinyl estradiol/0.05 mg levonorgestrel (6 days), 40 μg ethinyl estradiol/0.075 mg levonorgestrel (5 days), 30 μg ethinyl estradiol/0.125 mg levonorgestrel (10 days); (iv) norgestimate 0.22 mg = 35 μg ethinyl estradiol/0.18 mg (7 days), 0.215 mg (7 days), 0.25 mg (7 days) norgestimate.
ePheterogeneity < 0.05 comparing recent users of the formulation to recent users of other formulations.