Researchers claim breast cancer rate is linked to HRT

Researchers in the US have claimed that a decline in the amount of women taking hormone replacement therapy (HRT) is linked to a decline in new breast cancer cases, reported The Daily Telegraph and the Daily Mail .

Millions of women worldwide abandoned HRT following a study published in 2002 that linked it with an increased risk of heart disease, stroke and cancer. The newspapers said that this new research has reignited the row over the safety of HRT.

Both articles correctly state that the corresponding drop in HRT uptake and breast cancer levels in the US is not matched in the UK. In fact, British breast cancer rates have been rising despite a fall in HRT use.

The new research published this week suggests a link between the reduction in rates of both HRT use and breast cancer. Any interpretation of the results of this study need to take the design of the study into account. This is a time trend study and as such, only considers populations and not individuals. Therefore, we cannot associate a woman's use of HRT with her individual breast cancer risk.

The causes of breast cancer are complex, and although this study has exposed an area for further examination, further long-term studies would better reveal what effect taking HRT has on a woman's risk of breast cancer.

Where did the story come from?

The study was by K Kerlikowske and colleagues for the National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium, who also provided funding. The study was published in the peer- reviewed Journal of the National Cancer Institute .

What kind of scientific study was this?

This was a serial (or repeated) cross-sectional study designed to look into whether the decline in rates of breast cancer in the US were linked to a decline in HRT use or to a decline in mammography screening.

The researchers collected data from 603,411 mammography examinations on 232,212 women between the ages of 50 and 69 undergoing screening in four registries in the US between 1997 and 2003. None of the women had a prior diagnosis of breast cancer. Information on health, including gynaecological history and current HRT use, was collected at the time of the mammogram (most women had two scans during the period of the study).

Researchers then looked at the number of women who were diagnosed with breast cancer (invasive cancer [oestrogen-receptor positive or negative] or early pre-invasive cancer of the milk ducts) within 12 months of the screening examination.

From this information they used mathematical methods to calculate quarterly rates of breast cancer and HRT use per 1,000 mammograms, adjusting for other factors that may have an influence upon results such as age, registry and time between scans.

What were the results of the study?

The researchers found that rates of HRT use started to decline significantly between 2000 and 2002 (about the same time as other studies were published linking HRT to increased risk of breast cancer) and then declined even more rapidly between 2002 to the end of 2003.

The rates of invasive breast cancer were then found to have started to decline between 2001 and 2003; ductal carcinoma in situ rates stabilised; oestrogen-receptor positive rates declined between 2001 and 2003 but began to show a small increase again at the start of 2003; and oestrogen-receptor negative rates stabilised.

What interpretations did the researchers draw from these results?

The researchers suggest that the decline in HRT use has contributed to the significant decline in the rates of oestrogen-receptor positive invasive breast cancer. They say that although rates of mammography uptake among the population have also declined over this time period, the fact that this study has only examined screened women is likely to have taken that into account.

The researchers speculate that these possible links could be explained by the fact that HRT promotes fast tumour growth, and therefore ceasing to take HRT may slow the progression of breast cancer and may be causing the apparent decline in cancer rate. The researchers advise women who require HRT to use the therapy for the shortest time possible “to minimise the chance of an increase in breast cancer risk”.

What does the NHS Knowledge Service make of this study?

This repeated cross-sectional study provides quite reliable data on the number of new cases of breast cancer and HRT use among a large population of women. However, there are several points that need to be considered:

• This study cannot prove that the decrease in HRT use is linked to the decrease in invasive breast cancer rates. The researchers appear to have looked at time trends of HRT use and time trends of breast cancer. Though they do take into account various factors including age, there are a number of additional factors, that could be contributing to the observed trends.
• This type of study cannot show if there is a cause and effect relationship in what is being examined, because it only looks at what is happening at a population level rather than at the individual level. In this particular study, this means that the information on an individual's HRT use and disease state are not linked. Therefore we can never be sure whether the population of women who stopped using HRT are the same ones whose breast cancer rates are falling. Rates could be staying the same in this group and be falling in another.

The causes of breast cancer are complex, including genetic, gynaecological and medical factors. This study has exposed an area for further examination of how hormone use affects breast cancer risk. However, we cannot conclude from this study that a decline in the use of HRT is linked to a decline in the rates of diagnosed breast cancer in the US.