Long term use of combined hormone replacement therapy (HRT) doubles the risk of breast cancer, according to a major epidemiological study published last week that showed for the first time the higher risk with combined oestrogen and progestogen treatment.
Figure 1.
From 1996 to 2001 the million women study recruited 1 084 110 women in the United Kingdom aged 50-64 years. When they were invited to attend for routine mammography the women were asked to complete a questionnaire that included questions about their use of HRT. They were then followed up for mortality and incidence of cancer.
The results of the study, published in the Lancet (2003;362: 419-27), showed that current users of all types of HRT, including oestrogen only, combined oestrogen and progestogen, and tibolone (synthetic hormone treatment), had a higher risk of breast cancer than women who had never used HRT (adjusted relative risk 1.66 (95% confidence interval 1.58 to 1.75; P<0.0001)). The risk of breast cancer increased with longer use of HRT, but the effect seemed to wear off within a few years of stopping treatment. Also, the relative risk of death was 22% higher in current users than in women who had never used HRT (relative risk 1.22 (1.00 to 1.48; P=0.05)).
The risk was even higher in women who used combined HRT—the type of HRT that is generally recommended for women with a uterus (relative risk 2.00 (1.88 to 2.12; P<0.001)). This means that for every 1000 post-menopausal women taking combined HRT for 10 years there would be 19 extra cases of breast cancer, while oestrogen only HRT would be associated with an extra five cases. The researchers estimated that use of HRT in women aged 50-64 years has resulted in 20 000 extra cases of breast cancer over the past decade, of which 15 000 would be associated with combined HRT.
Valerie Beral, professor of epidemiology at the Cancer Research UK's Epidemiology Unit, at the Radcliffe Infirmary, Oxford, and one of the study authors, said: “Since our results show a substantially greater increase in breast cancer with combined HRT, women need to weigh the increased risk of breast cancer caused by the addition of progestogen against the lowered risk of uterine cancer.”
Richard Sullivan, head of clinical programmes at Cancer Research UK, agreed: “Each decision to start HRT should be made on an individual basis between each woman and her doctor.” He pointed out that HRT speeds up—rather than causes—the onset of breast cancer, acting as “a promoter not an initiator.”
“The risk of breast cancer does not start to increase until after one year of HRT,” he said.