Table 4.
Doubling of sex steroids and SHBG and breast cancer risk: Nurses' Health Study II, 1999 to 2009
| All Cases* | Premenopausal at Diagnosis | Postmenopausal at Diagnosis | P het** | ||||
|---|---|---|---|---|---|---|---|
| cases/ | cases/ | cases/ | |||||
| controls | OR (95% CI) | controls | OR (95% CI) | controls | OR (95% CI) | ||
| FOLLICULAR | |||||||
| Estradiol | |||||||
| All cancers | 462/909 | 1.0 (0.9 to 1.2) | 340/677 | 1.1 (0.9 to 1.3) | 92/176 | 0.6 (0.4 to 0.9) | < 0.01 |
| Invasive | 299/909 | 1.0 (0.9 to 1.2) | 221/677 | 1.2 (1.0 to 1.4) | 62/176 | 0.6 (0.4 to 0.9) | < 0.01 |
| ER+/PR+ | 201/909 | 1.0 (0.8 to 1.2) | 152/677 | 1.2 (0.9 to 1.5) | 43/176 | 0.6 (0.4 to 0.9) | 0.01 |
| Free Estradiol | |||||||
| All cancers | 447/886 | 1.0 (0.8 to 1.1) | 330/668 | 1.1 (0.9 to 1.4) | 86/162 | 0.5 (0.4 to 0.8) | < 0.01 |
| Invasive | 288/886 | 0.9 (0.8 to 1.1) | 214/668 | 1.2 (0.9 to 1.5) | 57/162 | 0.5 (0.3 to 0.7) | < 0.01 |
| ER+/PR+ | 194/886 | 0.9 (0.8 to 1.1) | 146/668 | 1.2 (0.9 to 1.5) | 41/162 | 0.4 (0.3 to 0.7) | < 0.01 |
| Estrone | |||||||
| All cancers | 469/920 | 1.0 (0.8 to 1.3) | 347/692 | 1.0 (0.8 to 1.3) | 91/173 | 1.0 (0.6 to 1.7) | 0.83 |
| Invasive | 305/920 | 1.0 (0.8 to 1.2) | 227/692 | 0.9 (0.7 to 1.3) | 61/173 | 0.8 (0.5 to 1.4) | 0.85 |
| ER+/PR+ | 206/920 | 1.2 (0.9 to 1.5) | 156/692 | 1.1 (0.8 to 1.6) | 43/173 | 1.0 (0.6 to 1.8) | 0.95 |
| LUTEAL | |||||||
| Estradiol | |||||||
| All cancers | 479/959 | 1.0 (0.8 to 1.2) | 347/710 | 1.0 (0.8 to 1.3) | 98/190 | 1.1 (0.7 to 1.7) | 0.82 |
| Invasive | 316/959 | 1.2 (1.0 to 1.4) | 232/710 | 1.2 (1.0 to 1.6) | 67/190 | 1.1 (0.7 to 1.7) | 0.66 |
| ER+/PR+ | 215/959 | 1.2 (1.0 to 1.5) | 162/710 | 1.3 (1.0 to 1.8) | 47/190 | 1.2 (0.8 to 2.1) | 0.80 |
| Free estradiol | |||||||
| All cancers | 469/944 | 1.0 (0.8 to 1.2) | 339/702 | 1.0 (0.8 to 1.3) | 96/183 | 1.1 (0.7 to 1.7) | 0.61 |
| Invasive | 309/944 | 1.1 (0.9 to 1.4) | 227/702 | 1.2 (0.9 to 1.5) | 65/183 | 1.0 (0.7 to 1.7) | 0.52 |
| ER+/PR+ | 209/944 | 1.2 (0.9 to 1.5) | 157/702 | 1.2 (0.9 to 1.7) | 46/183 | 1.3 (0.8 to 2.3) | 0.88 |
| Estrone | |||||||
| All cancers | 500/1005 | 1.0 (0.8 to 1.2) | 366/751 | 0.9 (0.7 to 1.2) | 99/194 | 1.3 (0.8 to 2.1) | 0.22 |
| Invasive | 328/1005 | 1.1 (0.9 to 1.4) | 242/751 | 1.0 (0.8 to 1.3) | 67/194 | 1.4 (0.8 to 2.2) | 0.34 |
| ER+/PR+ | 221/1005 | 1.1 (0.8 to 1.4) | 167/751 | 1.0 (0.7 to 1.4) | 47/194 | 1.5 (0.9 to 2.7) | 0.26 |
| Progesterone | |||||||
| All cancers | 501/1009 | 1.0 (0.9 to 1.1) | 368/753 | 1.0 (0.9 to 1.2) | 96/193 | 0.9 (0.7 to 1.1) | 0.24 |
| Invasive | 329/1009 | 1.0 (0.9 to 1.1) | 243/753 | 1.1 (0.9 to 1.2) | 66/193 | 0.8 (0.7 to 1.0) | 0.29 |
| ER+/PR+ | 222/1009 | 1.0 (0.9 to 1.1) | 168/753 | 1.0 (0.9 to 1.2) | 46/193 | 0.8 (0.6 to 1.0) | 0.42 |
| LUTEAL AND UNTIMED | |||||||
| Testosterone | |||||||
| All cancers | 623/1245 | 1.2 (1.0 to 1.4) | 417/858 | 1.1 (0.9 to 1.4) | 141/271 | 1.3 (0.8 to 2.0) | 0.52 |
| Invasive | 421/1245 | 1.2 (1.0 to 1.5) | 278/858 | 1.1 (0.8 to 1.4) | 100/271 | 1.8 (1.1 to 2.8) | 0.16 |
| ER+/PR+ | 290/1245 | 1.3 (1.0 to 1.7) | 192/858 | 1.2 (0.9 to 1.7) | 70/271 | 1.9 (1.1 to 3.4) | 0.41 |
| Free testosterone | |||||||
| All cancers | 617/1237 | 1.0 (0.9 to 1.1) | 414/853 | 1.0 (0.8 to 1.2) | 138/267 | 1.2 (0.8 to 1.8) | 0.23 |
| Invasive | 416/1237 | 1.0 (0.8 to 1.2) | 276/853 | 0.9 (0.7 to 1.1) | 97/267 | 1.3 (0.9 to 1.9) | 0.24 |
| ER+/PR+ | 287/1237 | 1.1 (0.9 to 1.3) | 190/853 | 1.0 (0.8 to 1.3) | 69/267 | 1.7 (1.0 to 2.6) | 0.22 |
| DHEAS | |||||||
| All cancers | 628/1254 | 1.1 (1.0 to 1.2) | 422/861 | 1.1 (0.9 to 1.2) | 141/276 | 1.1 (0.8 to 1.4) | 0.71 |
| Invasive | 423/1254 | 1.1 (0.9 to 1.2) | 280/861 | 1.0 (0.9 to 1.2) | 100/276 | 1.1 (0.8 to 1.5) | 0.38 |
| ER+/PR+ | 291/1254 | 1.2 (1.0 to 1.4) | 193/861 | 1.1 (0.9 to 1.4) | 70/276 | 1.3 (0.9 to 1.9) | 0.22 |
| SHBG | |||||||
| All cancers | 624/1246 | 1.1 (1.0 to 1.3) | 421/859 | 1.2 (1.0 to 1.4) | 138/270 | 0.9 (0.7 to 1.4) | 0.27 |
| Invasive | 420/1246 | 1.2 (1.0 to 1.4) | 280/859 | 1.2 (1.0 to 1.5) | 97/270 | 1.0 (0.7 to 1.5) | 0.66 |
| ER+/PR+ | 290/1246 | 1.1 (0.9 to 1.3) | 193/859 | 1.2 (0.9 to 1.5) | 69/270 | 0.9 (0.6 to 1.3) | 0.37 |
*Includes women of all menopausal statuses at diagnosis (premenopausal, postmenopausal and unknown). **Phet represents heterogeneity between premenopausal vs. postmenopausal status at diagnosis, among women premenopausal at blood collection. All cancers: Conditional logistic regression for all cancers controlling for age at menarche, parity/age at first birth, BMI at age 18, family history of breast cancer, history of benign breast disease. Invasive, ER+/PR+ tumors: Unconditional logistic regression for invasive and ER+/PR+ disease controlling for factors listed above and matching factors.