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Use of hormone replacement therapy (HRT) and risk of breast cancer

9 November 2020

Use of hormone replacement therapy (HRT) and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases [1]. A Critique.

Prepared by Nick Panay & Susan Davis on behalf of the International Menopause Society

Summary

Design and Methods
 
This paper describes two nested case-control studies using data from the two largest UK primary care databases. QResearch and Clinical Practice Research Datalink (CPRD) GOLD, utilising linked data from Hospital Episode Statistics (HES), Office for National Statistics (ONS) mortality data and cancer registry data (QResearch only). From the QResearch database, all cases of incident breast cancer were identified using general practice, hospital admission, mortality, and cancer registry records. From CPRD, when linked general practice, hospital admission (up to 31 December 2017), and mortality data records (up to 13 February 2018) were used to identify cases, and, when not linked, general practice records only. HRT prescription information was extracted for all estrogens, progestogens, and tibolone from practice records.
 
Results
 
59 999 and 38 612 (98 611) cases of breast cancer were identified in QResearch and CPRD, respectively, matched by age to 457 498 female controls. Compared with never use, long term use of systemic HRT (>/= 5 years) was found to be associated with an increased risk of breast cancer. The adjusted OR was 1.15 (95% CI 1.09 to 1.21) in women using estrogen and 1.79 (1.73 to 1.85) for combined estrogen and progestogen therapy. In those using combined estrogen and progestogen therapy, the increased risk was highest for norethisterone (1.88; 1.79 to 1.99) and lowest for dydrogesterone (1.24; 1.03 to 1.48). Past long term estrogen therapy and past short term combined therapy were not associated with an increased risk as opposed to past long term combined MHT usage, which remained slightly increased (1.16; 1.11 to 1.21). In terms of absolute numbers, this equated to 3-8 extra cases per 10 000 women-years with estrogen-only and 9-36 extra cases per 10 000 women-years in estrogen and progestogen users, depending on the age group. No increase in risk was associated with vaginal estrogen preparations.

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