Use of hormone replacement therapy ups breast cancer risk

A UK study has released further evidence of an increased risk of breast cancer associated with the use of hormone replacement therapy (HRT), with the levels of risk varying among HRT types and becoming higher for combined treatments and longer duration of use.

“This large observational study of HRT and breast cancer risk based on two large primary care databases analysed in an identical manner has confirmed the excess risk to be attributable mostly to combined treatments, with the lowest risks associated with use of the least commonly prescribed dydrogesterone,” the researchers said. “Rarely prescribed tibolone also showed low increased risks.”

Two nested case-control studies were conducted in UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data.

A total of 98,611 women aged 50–79 years with a primary diagnosis of breast cancer between 1998 and 2018 were included. The researchers matched the participants by age, general practice, and index date to 457,498 controls.

Of the women, 33,703 (34 percent) with a diagnosis of breast cancer and 134,391 (31 percent) controls had used HRT prior to 1 year before the index date. In recent users with >5 years’ duration, oestrogen-only therapy (adjusted odds ratio [aOR], 1.15, 95 percent confidence interval [CI], 1.09–1.21) and combined oestrogen and progestogen therapy (aOR, 1.79, 95 percent CI, 1.73–1.85) both correlated with elevated risks of breast cancer compared with never use. [BMJ 2020;371:m3873]

The increased risk for combined progestogens was highest for norethisterone (aOR, 1.88, 95 percent CI, 1.79–1.99) and lowest for dydrogesterone (aOR, 1.24, 95 percent CI, 1.03–1.48).

Notably, no risk increase was associated with past long-term use of oestrogen-only therapy and past short-term (<5 years) use of oestrogen-progestogen therapy. However, the increased risk associated with past long-term oestrogen-progestogen use persisted (aOR, 1.16, 95 percent CI, 1.11–1.21).

Furthermore, between three (in younger women) and eight (in older women) additional cases per 10,000 women years would be expected in recent oestrogen-only users, and between nine and 36 additional cases per 10,000 women years in oestrogen-progestogen users. For past oestrogen-progestogen users, between two and eight more cases per 10,000 women years could be expected.

“Our estimates were consistent with previous observational studies,” the researchers noted. [Cancer Epidemiol Biomarkers Prev 2016;25:1464-1473]

In the Million Women study, for instance, slightly higher risks were found compared with the current findings. However, the said study only covered a selected population of women who had undergone mammography and only a single baseline questionnaire was used to collect information. [Lancet 2003;362:419-427; J Natl Cancer Inst 2011;103:296-305]

“Our results add more evidence to the existing knowledge base and should help doctors and women to identify the most appropriate HRT formulation and treatment regimen, and provide more consistently derived information for women’s health experts, healthcare researchers, and treatment policy professionals,” the researchers said.