Nottingham, UK—Combined hormone replacement therapy (HRT) and longer duration of use most increase risks for developing breast cancer, according to a new study finding that levels of risks varied between types of HRT.
The report in The BMJ provides new estimates of the increased risks of breast cancer associated with use of different HRT products in the United Kingdom.
University of Nottingham–led researchers confirm that HRT use is associated with increased risk of breast cancer, especially for older women. Yet, it also suggests that, for longer-term HRT use, the increased risks are lower than those reported in other recent research, including a meta-analysis that combined the results of 24 studies.
The current study also demonstrated a sharper decline in risks once HRT therapy has ended, compared with the same meta-analysis.
Two nested case-control studies were conducted with data from UK general practices and linked to hospital, mortality, social deprivation, and cancer-registry information.
Participants were 98,611 women aged 50-79 years with a primary diagnosis of breast cancer between 1998 and 2018. Those patients were matched by age, general practice, and index date to 457,498 female controls.
Among the participants, 33 703 (34%) with a diagnosis of breast cancer and 134,391 (31%) controls had used HRT prior to 1 year before the index date.
Defined as main outcomes were breast cancer diagnosis from general practice, mortality, hospital, or cancer-registry records. Results indicate that, compared with never use, in recent users (less than 5 years) with long-term use (5 or more years), estrogen-only therapy and combined estrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 [95% CI, 1.09-1.21] and 1.79 [95% CI, 1.73-1.85]), respectively).
Researchers point out that, for combined progestogens, the increased risk was highest for norethisterone (1.88 [95% CI, 1.79-1.99]) and lowest for dydrogesterone (1.24 [95% CI, 1.03-1.48]).
The study also concludes that past long-term use of estrogen-only therapy and past short-term use of estrogen-progestogen therapy were not associated with increased risk. Yet, the authors explain that the risk associated with past long-term estrogen-progestogen use, however, remained increased (1.16 [95% CI, 1.11-1.21]).
Researchers calculate that, in recent estrogen-only users, between three (in younger women) and eight (in older women) extra cases per 10,000 women-years would occur, and in estrogen-progestogen users between nine and 36 extra cases per 10,000 women-years would result from the therapy.
They add that, for past estrogen-progestogen users, results indicate between two and eight extra cases per 10,000 women-years.
“This study has produced new generalizable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK,” the authors conclude. “The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.”
“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 add.
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