Long term hormone replacement therapy with estradiol alone is linked to breast cancer

Abstract

Research question What are the risks of breast cancer associated with different types of oestrogen only hormone replacement therapy?

Answer Women who use oral or transdermal estradiol for more than five years have a higher risk of breast cancer than the general population.

Why did the authors do the study? The evidence linking oestrogen only hormone replacement therapy to breast cancer is mixed. These authors wanted to find out if the risk varied with the type of oestrogen, the dose, or the route of administration. They focused on estradiol, the oestrogen most commonly used by women in Europe.

What did they do? They linked data from a Finnish register containing records of all reimbursements for oestrogen only hormone replacement therapy, with data from the Finnish cancer registry, which is thought to be almost 100% complete. Most of the reimbursements were for estradiol pills, patches, or gels. The few women prescribed conjugated equine oestrogens were excluded from the analysis. The authors looked for associations between breast cancer incidence and hormone use by calculating standardised incidence ratios—the ratio of observed to expected cases of breast cancer among women using systemic estradiol (oral or transdermal), oral estriol, or vaginal oestrogen creams. They did separate analyses for short term (up to five years) and long term (five years or more) use. The final cohort included 110 984 postmenopausal women aged over 50 who had used oestrogen alone for more than six months. All the women had had a hysterectomy.

What did they find? Women who took estradiol orally or transdermally for less than five years were no more likely to get breast cancer than women of a similar age in the general Finnish population (standardised incidence ratio 0.93 (95% CI 0.8 to 1.04)), but longer use of systemic therapy was associated with a significant rise in breast cancer incidence (ratio 1.44 (1.29 to 1.59)). Vaginal oestrogens and oral estriol seemed safe, even when used for more than five years.

The risk associated with long term use of systemic estradiol didn't vary significantly with the dose. Long term use was associated with both lobular and ductal cancers, and with both early and later stage disease.

What does it mean? These data suggest a link between breast cancer and long term treatment with oral or transdermal estradiol in postmenopausal Finnish women. It's possible that the hormone encourages the growth of breast cancers directly, but it's also possible that confounding factors such as body weight, age at the birth of the first child, and parity were at least partly responsible for the inflated risk. The authors were unable to account for any of these factors in their analysis, so we can't say for certain that the observed association was causal. Detection bias could also be relevant here. Women taking hormone replacement therapy may be more likely than other women to have breast examinations and mammograms.