Elsevier

The Lancet

Volume 362, Issue 9382, 9 August 2003, Pages 419-427
The Lancet

Articles
Breast cancer and hormone-replacement therapy in the Million Women Study

https://doi.org/10.1016/S0140-6736(03)14065-2Get rights and content

Summary

Background

Current use of hormone-replacement therapy (HRT) increases the 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

1084110 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 of 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 for other types of HRT (p<0·0001). Results varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increased separately 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 (15–23) additional cancers per 1000 users of oestrogen-progestagen combinations. Use of HRT by women aged 50–64 years in the UK over the past decade has resulted in an estimated 20000 extra breast cancers, 15000 associated with oestrogen-progestagen; the extra deaths cannot yet 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.

Introduction

Results from randomised controlled trials and from observational studies show that current and recent use of hormone-replacement therapy (HRT) increases the risk of breast cancer.1, 2, 3, 4 However, the effect of HRT on mortality from breast cancer is unclear1, 2, 3, 4, 5 and use of HRT preparations containing oestrogen-progestagen combinations may be associated with a greater risk of breast cancer than preparations containing oestrogen alone.6, 7, 8, 9, 10 The Million Women Study, a cohort study of a quarter of British women aged 50–64 years, was set up chiefly to investigate the relation between various patterns of use of HRT and breast cancer incidence and mortality.11

Section snippets

Data collection and definitions

The National Health Service Breast Screening Programme (NHSBSP) invites all women in the UK aged 50–64 years for routine screening once every 3 years. From May, 1996, to March, 2001, the NHS breast-screening centres participating in the Million Women Study included the study questionnaire together with their letter of invitation for routine mammography.11 This letter is generally posted 2–6 weeks before the woman's screening appointment. The questionnaire is returned before women are screened

Results

These results are based on the follow-up of 1084110 women recruited between 1996 and 2001, who were flagged on the NHS Central Registers and who had not been registered as having had cancer before they joined the Million Women Study. The average age of the women at recruitment was 55·9 years, and the average period of follow-up was 2·6 years for analyses of the cancer incidence and 4·1 years for analyses of mortality. During the follow-up period, 9364 incident invasive breast cancers and 637

Discussion

The results of this study confirm previous findings that current and recent use of HRT increases the risk of breast cancer,1, 2, 3, 4, 5, 6, 7, 8, 9, 10 but also provides new and reliable information about the effects of various patterns of use. The Million Women Study was set up to examine the effect of HRT on breast cancer incidence and mortality. Study participants were recruited at the time of their triennial invitation for routine mammography by the NHSBSP. The programme provides a routine

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