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18th November 2021
Hormone replacement therapy (HRT) use for the management of menopausal symptoms in women with a history of breast cancer is associated with a significant increase in the risk of disease recurrence according to a meta-analysis by researchers from Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Although there have been major advances in the treatment of breast cancer, the blocking of oestrogen is associated with several adverse effects which negatively impact on a patient’s quality of life. HRT use is the most effective treatment for symptoms related to a reduction in the level of oestrogen although its use in breast cancer survivors is generally avoided. Among healthy women, the use of oestrogen only HRT leads to a reduced risk of breast cancer but when oestrogen is combined medroxyprogesterone, the risk is increased. Though it is generally advised that the use of HRT is avoided in patients with a history of breast cancer it has been suggested that there is insufficient evidence to contra-indicate HRT in breast cancer survivors.
With some uncertainty over whether HRT increases the risk in breast cancer survivors who experience oestrogen depletion-related symptoms, the Italian team decided to perform a systematic review and meta-analysis to assess the overall safety of systemic HRT use and its impact on disease recurrence in breast cancer survivors. They searched all of the main databases but restricted their search to articles published in English, randomised, placebo-controlled trials with breast cancer survivors and any studies reporting on the recurrence of breast cancer.
The literature search identified 12 studies of which, only 4 were included in the final analysis examining the effect of HRT on 4050 breast cancer survivors. All trials had randomised patients to either HRT or placebo with a total of 2022 patients randomised to HRT, either oestrogen/progestogen combinations or tibolone.
There was a low degree of heterogeneity in studies and compared to the placebo group, the use of HRT significantly increased the risk of breast cancer recurrence (hazard ratio, HR = 1.46, 95% CI 1.12 – 1.91, p = 0.006). In subgroup analysis, among patients with hormone receptor-positive tumours, the risk of disease recurrence was also significantly increased in those using hormonal therapy (HR = 1.80, 95% CI 1.15 – 2.82, p = 0.010). In contrast, in patients with hormone receptor-negative disease, there was no significant increase in risk (HR = 1.19, 95% CI 0.80 – 1.77, p = 0.39). In a further analysis, the risk of breast cancer recurrence was no different between combined HRT and tibolone (HR = 1.51 95% CI 0.84 – 2.72).
Based on these findings, the authors concluded that future research should focus on finding alternatives to hormone replacement therapy for women who have survived breast cancer yet experience symptoms related to oestrogen deficiency.
Poggio F et al. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat 2021