Table 1.
Demographic and treatment characteristics of 17,903 female 5-year childhood cancer survivors (primary cancer diagnosis year 1946–2012) overall and by subsequent breast cancer status
| Characteristic | Total (n = 17,903) | Subsequent breast cancera (n = 782) | No subsequent breast cancer (n = 17,121) |
|---|---|---|---|
| No. (%) | No. (%) | No. (%) | |
| Primary childhood cancerb | |||
| Leukemia | 4,574 (25.5) | 81 (10.4) | 4,493 (26.2) |
| Non-Hodgkin lymphoma | 1,097 (6.1) | 37 (4.7) | 1,060 (6.2) |
| Hodgkin lymphoma | 2,101 (11.7) | 405 (51.8) | 1,696 (9.9) |
| Central nervous system tumor | 2,946 (16.5) | 14 (1.8) | 2,932 (17.1) |
| Neuroblastoma | 1,657 (9.3) | 15 (1.9) | 1,642 (9.6) |
| Retinoblastoma | 426 (2.4) | 2 (0.3) | 424 (2.5) |
| Renal tumor | 1,372 (7.7) | 45 (5.8) | 1,327 (7.8) |
| Bone tumor | 1,459 (8.1) | 106 (13.6) | 1,353 (7.9) |
| Soft tissue tumor | 1,405 (7.8) | 55 (7.0) | 1,350 (7.9) |
| Germ cell tumor | 440 (2.5) | 9 (1.2) | 431 (2.5) |
| Other malignant epithelial | 297 (1.7) | 11 (1.4) | 286 (1.7) |
| Otherc | 129 (0.7) | 2 (0.2) | 127 (0.8) |
| Cumulative doxorubicin dose (mg m−2) | |||
| 0 | 11,170 (62.4) | 431 (55.1) | 10,739 (62.7) |
| <100 | 912 (5.1) | 16 (2.0) | 896 (5.2) |
| 100–199 | 1,795 (10.0) | 69 (8.8) | 1,726 (10.1) |
| 200–299 | 1,026 (5.7) | 67 (8.6) | 959 (5.6) |
| 300–399 | 1,012 (5.7) | 64 (8.2) | 948 (5.5) |
| ≥400 | 779 (4.4) | 58 (7.4) | 721 (4.2) |
| Unknownd | 1,209 (6.8) | 77 (9.8) | 1,132 (6.6) |
| Cumulative daunorubicin dose (mg m−2) | |||
| 0 | 14,630 (81.7) | 684 (87.5) | 13,946 (81.5) |
| <100 | 623 (3.5) | 7 (0.9) | 616 (3.6) |
| 100–199 | 953 (5.3) | 16 (2.0) | 937 (5.5) |
| ≥200 | 645 (3.6) | 17 (2.2) | 628 (3.7) |
| Unknowne | 1,052 (5.9) | 58 (7.4) | 994 (5.8) |
| Epirubicin | |||
| No | 16,637 (92.9) | 717 (91.7) | 15,920 (93.0) |
| Yes | 325 (1.8) | 9 (1.2) | 316 (1.8) |
| Unknown | 941 (5.3) | 56 (7.2) | 885 (5.2) |
| Idarubicin | |||
| No | 16,843 (94.1) | 725 (92.7) | 16,118 (94.1) |
| Yes | 107 (0.6) | 1 (0.1) | 106 (0.6) |
| Unknown | 953 (5.3) | 56 (7.2) | 897 (5.2) |
| CEDf (mg m−2) | |||
| 0 | 7,951 (44.4) | 301 (38.5) | 7,650 (44.7) |
| <6,000 | 3,069 (17.1) | 94 (12.0) | 2,975 (17.4) |
| 6,000–17,999 | 3,899 (21.8) | 192 (24.6) | 3,707 (21.7) |
| ≥18,000 | 1,117 (6.2) | 47 (6.0) | 1,070 (6.2) |
| Unknown | 1,867 (10.4) | 148 (18.9) | 1,719 (10.0) |
| Chest radiotherapy fields and dosesg | |||
| No chest radiotherapy | 13,004 (72.6) | 250 (32.0) | 12,754 (74.5) |
| High-dose mantle (≥36 Gy; median: 40 Gy, IQR: 39–44 Gy)h | 698 (3.9) | 238 (30.4) | 460 (2.7) |
| Low-dose mantle (<36 Gy; median: 26 Gy, IQR: 21–30 Gy)h | 524 (2.9) | 93 (11.9) | 431 (2.5) |
| Mediastinal (median: 26 Gy, IQR: 21–36 Gy)h | 469 (2.6) | 33 (4.2) | 436 (2.5) |
| TBI (median: 12 Gy, IQR: 11–13 Gy)h | 371 (2.1) | 22 (2.8) | 349 (2.0) |
| Whole lung (median: 16 Gy, IQR: 12–23 Gy)h | 184 (1.0) | 23 (2.9) | 161 (0.9) |
| Other (median: 28 Gy, IQR: 21–36 Gy)h | 1,316 (7.4) | 63 (8.1) | 1,253 (7.3) |
| Unknown | 1,337 (7.5) | 60 (7.7) | 1,277 (7.5) |
| Pelvic radiotherapy dosei | |||
| No pelvic radiotherapy | 13,727 (76.7) | 505 (64.6) | 13,222 (77.2) |
| <10 Gy | 142 (0.8) | 6 (0.8) | 136 (0.8) |
| 10–19 Gy | 594 (3.3) | 24 (3.1) | 570 (3.3) |
| 20–29 Gy | 719 (4.0) | 38 (4.9) | 681 (4.0) |
| 30–39 Gy | 767 (4.3) | 82 (10.5) | 685 (4.0) |
| ≥40 Gy | 713 (4.0) | 72 (9.2) | 641 (3.7) |
| Unknown | 1,241 (6.9) | 55 (7.0) | 1,186 (6.9) |
| Age at diagnosis of primary cancer (years) | |||
| <5 | 7,376 (41.2) | 66 (8.4) | 7,310 (42.7) |
| 5–9 | 3,788 (21.2) | 65 (8.3) | 3,723 (21.7) |
| 10–14 | 3,930 (22.0) | 273 (34.9) | 3,657 (21.4) |
| 15–21 | 2,809 (15.7) | 378 (48.3) | 2,431 (14.2) |
| Treatment subgroupsj | |||
| Anthracyclinek and chest radiotherapy | 1,634 (9.1) | 163 (20.8) | 1,471 (8.6) |
| Anthracycline and no chest radiotherapy | 5,714 (31.9) | 156 (19.9) | 5,558 (32.5) |
| No anthracycline and chest radiotherapy | 1,962 (11.0) | 294 (37.6) | 1,668 (9.7) |
| No anthracycline and no chest radiotherapy | 7,096 (39.6) | 83 (10.6) | 7,013 (41.0) |
| Unknown | 1,497 (8.4) | 86 (11.0) | 1,411 (8.2) |
aIncluded both invasive and ductal carcinoma in situ breast cancer.
bBecause of the eligibility criteria of the cohort, the composition of primary cancer diagnosis groups in our pooled data may differ from the composition in underlying populations of childhood cancer survivors.
cIncluded the ICCC-3 classification groups ‘hepatic tumor’ (0 case/61 survivors), ‘other and unspecified’ (1 case/38 survivors), and ‘unclassified’ (1 case/30 survivors).
dThe unknown category under the variable ‘doxorubicin dose’ included both survivor groups with any doxorubicin (yes/no) unknown (56 cases/941 survivors) and with doxorubicin treatment but dose information unknown (21 cases/268 survivors).
eThe unknown category under the variable ‘daunorubicin dose’ included both survivor groups with any daunorubicin (yes/no) unknown (56 cases/953 survivors) and with daunorubicin treatment but dose information unknown (2 cases/99 survivors).
fCED calculation: CED (mg m−2) = 1.0 (cumulative cyclophosphamide dose (mg m−2)) + 0.244 (cumulative ifosfamide dose (mg m−2)) + 0.857 (cumulative procarbazine dose (mg m−2)) + 14.286 (cumulative chlorambucil dose (mg m−2)) + 15.0 (cumulative BCNU (carmustine) dose (mg m−2)) + 16.0 (cumulative CCNU (lomustine) dose (mg m−2)) + 40 (cumulative melphalan dose (mg m−2)) + 50 (cumulative Thio-TEPA (thiotepa) dose (mg m−2)) + 100 (cumulative nitrogen mustard dose (mg m−2)) + 8.823 (cumulative busulfan dose (mg m−2)).
gIncluded radiotherapy fields exposing (parts of) the chest. Radiation dose referred to the cumulative prescribed dose (including boost doses, if applicable), or slight variations, depending on definitions in the underlying cohorts25. Chest radiotherapy was categorized as the combination of chest radiation fields with the associated maximum chest radiotherapy dose below or above the median. The variable was classified as follows: high-dose mantle (median: 40 Gy, IQR: 39–44 Gy), low-dose mantle (median: 26 Gy, IQR: 21–30 Gy), mediastinal (median: 26 Gy, IQR: 21–36 Gy), TBI (median: 12 Gy, IQR: 11–13 Gy), whole lung (median: 16 Gy, IQR: 12–23 Gy), other (median: 28 Gy, IQR: 21–36 Gy) and unknown.
hDose represents the maximum cumulative prescribed chest dose (including boost doses, if applicable) of survivors classified in this group. This could include doses to chest field other than this category.
iIncluded radiotherapy fields exposing (parts of) the pelvis (including TBI). Radiation dose referred to the cumulative prescribed dose (including boost doses, if applicable), or slight variations, depending on definitions in the underlying cohorts25. The unknown category under the variable ‘pelvic radiotherapy dose’ included both survivor groups with any pelvic radiotherapy (yes/no) unknown (54 cases/1,212 survivors) and with pelvic radiotherapy treatment but dose information unknown (1 case/29 survivors).
jTreatment subgroup variable set to unknown if either of the treatment categories was unknown.
kAnthracyclines included doxorubicin, daunorubicin, epirubicin and idarubicin.