Table 2.
Associations between conjugated equine oestrogen and breast cancer incidence and mortality during and after the intervention in the Women's Health Initiative randomised trial
| Intervention Phase, N=10,739 (Events on or Before 29 Feb, 2004) |
Post-Intervention Phase1,N=9,671 (Events occurring 1 March, 2004–14 Aug, 2009) |
Overall (Events through 14 August, 2009) |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Oestrogen (n = 5,310) |
Placebo (n=5,429) |
Oestrogen (n=4,794) |
Placebo (n=4,877) |
Oestrogen (n=5,310) |
Placebo (n=5,429) |
||||||
| Follow-up time (months) | 85·5 | 85·9 | 47·1 | 47·2 | 128·2 | 128·5 | |||||
| Outcomes | N (%) | N (%) | HR2,3 (95% CI) | N (%) | N (%) | HR2,4 (95% CI) | P-diff5 | N (%) | N (%) | HR2,3 (95% CI) | P-het6 |
| Invasive Breast Cancer | 104 (0·28%) | 135 (0·35%) | 0·79 (0·61,1·02) | 47 (0·26%) | 64 (0·34%) | 0·75(0·51,1·09) | 0·76 | 151 (0·27%) | 199 (0·35%) | 0·77 (0·62,0·95) | |
| Histology7 | 0·33 | ||||||||||
| Ductal | 60 (0·16%) | 88 (0·23%) | 0·70 (0·51,0·98) | 26 (0·14%) | 43 (0·23%) | 0·62(0·38,1·01) | 0·63 | 86 (0·15%) | 131 (0·23%) | 0·67 (0·51,0·88) | |
| Lobular | 18(0·048%) | 12(0·031%) | 1·56 (0·75,3·24) | 2(0·011%) | 7 (0·038%) | 0·28(0·06,1·34) | 0·06 | 20 (0·036%) | 19 (0·033%) | 1·09 (0·58,2·04) | |
| Ductal and Lobular | 12 (0·032%) | 13 (0·034%) | 0·93 (0·42,2·03) | 7 (0·038%) | 5 (0·027%) | 1·38(0·44,4·34) | 0·55 | 19 (0·034%) | 18 (0·032%) | 1·06 (0·55,2·01) | |
| Other | 14 (0·037%) | 21 (0·055%) | 0·68 (0·34,1·33) | 12 (0·065%) | 9 (0·048%) | 1·37(0·58,3·25) | 0·22 | 26 (0·047%) | 30 (0·053%) | 0·88 (0·52,1·49) | |
| ER status7 | 0·78 | ||||||||||
| ER+ | 72 (0·19%) | 96 (0·25%) | 0·7 (0·57,1·05) | 38 (0·21%) | 53 (0·29%) | 0·72(0·48,1·10) | 0·79 | 110 (0·20%) | 149 (0·26%) | 0·75 (0·59,0·96) | |
| ER− | 19(0·051%) | 22 (0·058%) | 0·88 (0·48,1·63) | 6 (0·033%) | 9 (0·048%) | 0·70(0·25,1·96) | 0·68 | 25 (0·045%) | 31 (0·055%) | 0·81 (0·48,1·38) | |
| PR status7 | 0·34 | ||||||||||
| PR+ | 57 (0·15%) | 71 (0·19%) | 0·83 (0·58,1·17) | 35 (0·19%) | 41 (0·22%) | 0·86(0·55,1·36) | 0·91 | 92 (0·17%) | 112 (0·20%) | 0·84 (0·63,1·10) | |
| PR− | 32 (0·086%) | 43 (0·11%) | 0·76 (0·48,1·20) | 9 (0·049%) | 20 (0·11%) | 0·46(0·21,1·02) | 0·27 | 41 (0·074%) | 63 (0·11%) | 0·66 (0·45,0·98) | |
| HER2 overexpression7 | 0·045 | ||||||||||
| Yes | 18(0·048%) | 12(0·031%) | 1·58 (0·76,3·27) | 5 (0·027%) | 4 (0·022%) | 1·32(0·35,4·94) | 0·84 | 23 (0·041%) | 16 (0·028%) | 1·50 (0·79,2·83) | |
| No | 53 (0·14%) | 67 (0·18%) | 0·81 (0·56,1·16) | 36 (0·20%) | 54 (0·29%) | 0·67(0·44,1·03) | 0·50 | 89 (0·16%) | 121 (0·21%) | 0·74 (0·56,0·97) | |
| Triple-negative tumor7 | 0·26 | ||||||||||
| Yes | 12 (0·032%) | 8 (0·021%) | 1·54 (0·63,3·79) | 4 (0·022%) | 6 (0·032%) | 0·69(0·19,2·44) | 0·30 | 16 (0·029%) | 14 (0·025%) | 1·14 (0·56,2·34) | |
| No | 92 (0·25%) | 127 (0·33%) | 0·74 (0·57,0·97) | 43 (0·23%) | 58 (0·31%) | 0·75(0·51,1·12) | >0·99 | 135 (0·24%) | 185 (0·33%) | 0·74 (0·60,0·93) | |
| Stage7 | 0·19 | ||||||||||
| Local | 67 (0·18%) | 100 (0·26%) | 0·69 (0·51,0·94) | 34 (0·18%) | 44 (0·24%) | 0·79(0·50,1·24) | 0·67 | 101 (0·18%) | 144 (0·25%) | 0·72 (0·56,0·92) | |
| Regional or distant | 35 (0·094%) | 31(0·081%) | 1·15 (0·71, 1·86) | 13 (0·071%) | 18 (0·097%) | 0·72(0·36, 1·48) | 0·30 | 48 (0·086%) | 49 (0·086%) | 0·98 (0·66, 1·46) | |
| Grade7 | 0·56 | ||||||||||
| Well differentiated | 19(0·051%) | 26 (0·068%) | 0·74(0·41, 1·33) | 11 (0·060%) | 16 (0·086%) | 0·70 (0·32,1·51) | 0·91 | 30 (0·054%) | 42 (0·074%) | 0·72(0·45, 1·16) | |
| Moderately differentiated | 31 (0·083%) | 52 (0·14%) | 0·61(0·39,0·96) | 20 (0·11%) | 31 (0·17%) | 0·65 (0·37,1·14) | 0·91 | 51 (0·092%) | 83 (0·15%) | 0·62 (0·44, 0·88) | |
| Poorly differentiated | 29 (0·078%) | 40 (0·10%) | 0·75(0·46, 1·21) | 14 (0·076%) | 13 (0·070%) | 1·11 (0·52,2·37) | 0·40 | 43 (0·077%) | 53 (0·093%) | 0·83 (0·55, 1·24) | |
| Tumor size7 | 0·06 | ||||||||||
| ≤1 cm | 31 (0·083%) | 51 (0·13%) | 0·63 (0·40, 0·98) | 11 (0·060%) | 21 (0·11%) | 0·53 (0·26,1·11) | 0·70 | 42 (0·075%) | 72 (0·13%) | 0·60 (0·41, 0·87) | |
| 1 <2 cm | 35 (0·094%) | 52 (0·14%) | 0·69(0·45, 1·06) | 16 (0·087%) | 21 (0·11%) | 0·78 (0·41,1·50) | 0·77 | 51 (0·092%) | 73 (0·13%) | 0·71 (0·50, 1·02) | |
| 2+ cm | 25 (0·067%) | 23 (0·060%) | 1·10(0·63, 1·95) | 16 (0·087%) | 16 (0·086%) | 0·99 (0·49,1·97) | 0·79 | 41 (0·074%) | 39 (0·069%) | 1·05 (0·68, 1·63) | |
| Positive lymph nodes7 | 0·14 | ||||||||||
| No | 61 (0·16%) | 93 (0·24%) | 0·68 (0·49, 0·94) | 27 (0·15%) | 41 (0·22%) | 0·67 (0·41,1·09) | 0·94 | 88 (0·16%) | 134 (0·24%) | 0·67(0·51,0·88) | |
| Yes | 32 (0·086%) | 28 (0·073%) | 1·16(0·70, 1·92) | 11 (0·060%) | 16 (0·086%) | 0·69 (0·32,1·49) | 0·27 | 43 (0·077%) | 44 (0·077%) | 0·98(0·64, 1·49) | |
| All-Cause Mortality after | 7 (0·018%) | 12 (0·031%) | 0·60(0·22, 1·48) | 23 (0·087%) | 38 (0·14%) | 0·62 (0·36,1·03) | 0·92 | 30 (0·046%) | 50 (0·076%) | 0·62 (0·39, 0·97) | |
| Breast Cancer | |||||||||||
| Breast Cancer Deaths | 4 (0·011%) | 9 (0·023%) | 0·45 (0·12, 1·37) | 2 (0·008%) | 7 (0·026%) | 0·29 (0·04, 1·21) | 0·66 | 6 (0·009%) | 16 (0·024%) | 0·37(0·13, 0·91) | |
HR, hazard ratio; CI, confidence interval; ER, oestrogen receptor; PR, progesterone receptor;
Post-intervention phase includes data collected under extended follow-up (after 31 March, 2005). 3778(77·9%) of 4851 eligible participants randomised to conjugated equine oestrogen, and 3867(78·4%) of 4935 eligible participants randomized to placebo consented to extended follow-up.
From a proportional hazards model stratified by age group (50–54, 55–59, 60–69, 70–79), dietary modification randomisation arm.
Time to event measured from date of randomisation.
Time to event measured from 1 March, 2004.
P-diff based on tests for equality of the intervention and post-intervention phase hazard ratios in a proportional hazards model stratified by age group (50–54, 55–59, 60–69, 70–79), dietary modification randomisation arm, and trial phase (time-dependent) with time to event measured from date of randomisation.
P-het from a competing risks analysis that tests whether hazard ratios differ between tumor types.
Hazard ratios for a specific tumor characteristic are from proportional hazards model where incidence of tumor with alternate characteristics are censored. Tumor characteristics were missing on the following numbers of cases (active vs. placebo) for histology (0 vs. 1), ER status (16 vs. 19), PR status (18 vs. 24), HER2 over expression (39 vs. 62), stage (2 vs. 6), grade (27 vs. 21), tumor size (10 vs. 11), and positive lymph nodes (20 vs. 21). Eleven tumors of indeterminate size were found (7 vs. 4).