THE MILLION WOMEN STUDY

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Breast cancer and hormone replacement therapy in the Million Women Study.

Million Women Study Collaborators.

Lancet 2003; 362:419-427

Background Current use of hormone replacement therapy (HRT) increases incidence of breast cancer. The Million Women Study was set up to investigate the effects of specific types of HRT on incident and fatal breast cancer.

Methods 1,084,110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death.

Findings Half the women had used HRT; 9364 incident invasive breast cancers and 637 breast cancer deaths were registered after an average of 2.6 and 4.1 years follow-up, respectively. Current users of HRT at recruitment were more likely than never users to develop breast cancer (adjusted relative risk 1.66 [95% CI 1.58-1.75],p<0.0001) and die from it (1.22 [1.00-1.48], p=0.05). Past users of HRT were however, not at an increased risk of incident or fatal disease (1.01 [0.94-1.09] and 1.05 [0.82-1.34], respectively). Incidence was significantly increased for current users of preparations containing oestrogen only (1.30 [1.21-1.40], p<0.0001), oestrogen-progestagen (2.00 [1.88-2.12], p<0.0001) and tibolone (1.45 [1.25-1.68], p<0.0001), but the magnitude of the associated risk was substantially greater for oestrogen-progestagen than other types of HRT (p<0.0001). Results varied little between specific oestrogens and prgestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increeased seperately for oral, transdermal, and implanted oestrogen-only formulations (1.32 [1.21-1.45]; 1.24 [1.11-1.39]; and 1.65 [1.26-2.16], respectively; all p<0.0001). In current users of each type of HRT the risk of breast cancer increased with increasing total duration of use. 10 years use of HRT is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 users of oestrogen-only preparations and 19 (18-20) additional cancers per 1000 users of oestrogen-progestgen combinations. Use of HRT by women aged 50-64 years in the UK over the past decade has resulted in an estimated 20,000 extra breast cancers, 15,000 associated with oestrogen-progestagen; the extra deaths cannot be reliably estimated.

Interpretation Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.

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