A 2021 systematic review and meta-analysis in the general population (n = 4050) showed a two-to three-fold increased risk of recurrent or new breast cancer in HRT users after estrogen receptor-positive but not estrogen receptor-negative breast cancer.32 When HRT is contraindicated or avoided there are several effective non-pharmacological and non-hormonal treatments for vasomotor symptoms.33,34. The gene discussed is ESR1; the disease is breast cancer.