HRT and breast cancer – the link questioned as study flaws are reported

By Dr. Ananya Mandal, MDJan 18 2012

There is a renewed doubt over the link between hormone replacement therapy and breast cancer after researchers cast aspersions over its justification.

The “Million Women Study” of 2003 concluded that taking HRT doubled a woman's risk of developing breast cancer. This risk has been underlined by further findings from the study, funded by Cancer Research UK.

In the latest report scientists writing in the Journal of Family Planning and Reproductive Health said there were flaws in the study which they claimed would have skewed the findings. “If the evidence was unreliable, the only effect of its massive size would have been to confer spurious statistical authority to doubtful findings,” critics said.

The Million Women Study was carried out by researchers in Oxford with the support of Cancer Research UK and the NHS, it drew on new cases of breast cancer arising in women invited for breast screening in the UK between 1966 and 2001. It showed a high risk of breast cancer with HRT and undermined the confidence in HRT. According to the charity, Women's Health Concern, the number of women taking HRT fell by 66%.

The new review, carried out by Professor Samuel Shapiro from the University of Cape Town, South Africa, and colleagues, found several design flaws which they said would have skewed the results. They write that some women enrolled on the study could have already had cancer - but these participants were not excluded. Also because participants were already in a breast screening programme, they were more likely to be HRT users who were already aware of signs of cancer such as breast lumps. This would have led to more cancers being found, the authors said. They add that crucial data was missing. In one of four reports on the Million Women Study, follow-up figures for between 57% and 62% of the study participants were unavailable. The authors conclude that HRT may or may not increase the risk of breast cancer, but the Million Women Study did not establish that it does.

They write, “The name ‘Million Women Study’ implies an authority beyond criticism or refutation. Many commentators, and the investigators, have repeatedly stressed that it was the largest study of HRT and breast cancer ever conducted…Yet the validity of any study is dependent on the quality of its design, execution, analysis and interpretation. Size alone does not guarantee that the findings are reliable…The MWS was an observational study, and it has the attendant problems and uncertainties intrinsic to such studies. If the evidence was unreliable, the only effect of its massive size would have been to confer spurious statistical authority to doubtful findings.”

Commenting on the results, Hazel Nunn, head of health information at Cancer Research UK, said to WebMD, “Studies suggest that in 2005 there were 1,400 fewer cases of breast cancer in the UK among women aged 50-59 than would have been if there had been no drop in HRT use…Women shouldn’t be unduly worried by this latest review of HRT and breast cancer risk. HRT can be an effective short-term treatment for menopausal symptoms - women taking it should try and use the lowest dose possible for as short a time as they need it.”

The charity Breakthrough Breast Cancer says HRT is an established factor which increases a woman’s risk of developing breast cancer and that other studies besides the Million Women Study, show that the link exists.

Dr Susie Jennings, senior policy officer at Breakthrough Breast Cancer, says in a statement, “Many studies have shown that HRT increases the risk of breast cancer and this study does not change that. It does suggest the risks may, in some instances, have been slightly overstated. However, we know that the risk of breast cancer starts to decrease as soon as a woman stops taking HRT. Anyone who has concerns about HRT should speak with their doctor. We hope the Breakthrough Generations Study, which is following 110,000 UK women over 40 years, will provide further clarity on this issue.”

In a joint statement, Professor Valerie Beral and Professor Richard Peto, from Oxford University, said, “HRT is one of the most important causes of breast cancer in the world and women can easily change their risk by stopping.” Prof Dame Valerie Beral added, “This paper is a re-statement of views held by many consultants to HRT manufacturers (as these authors are) attempting to dispute evidence about the adverse effects of HRT. The issues raised are not new and have been refuted previously. The authors omit to say that Million Women Study findings, of an increased risk of breast cancer in users of HRT, especially of estrogen-progestagen combinations, have been replicated in over 20 other studies. The totality of the worldwide evidence is now overwhelming. In line with the findings from these studies, the recent large decrease in HRT use has been followed in many countries by a nationwide decline in the incidence of breast cancer.”