Protocol to assess risk of breast cancer associated with use of hormone replacement therapy in real world settings: two nested case-control studies in primary care.

Hormone replacement therapy (HRT) is used to help women suffering from menopausal symptoms and reduce risk of osteoporosis. Although effective, the therapy may lead to an increased risk of breast cancer. Previous studies have not been powerful enough to investigate the risks associated with different types of HRT. The proposed nested case-control study aims to fill this gap. Women diagnosed with breast cancer between 1998 and 2018 will be matched to 5 controls without breast cancer by age, practice and calendar year. Excluding prescriptions in the year before the index date (date of diagnosis of breast cancer in the case), exposure to each type of HRT will be defined as at least one prescription for that HRT prior to the index date. Conditional logistic regression will be used to assess the risks associated with the different types of oestrogen and progestogen. The associations with duration, length of any gap since earlier use and method of application will also be analysed for the most common types of HRT