HRT use in women who have previously suffered from breast cancer is associated with a significantly increased risk of disease recurrence.
Hormone replacement therapy (HRT) use for the management of menopausal symptoms in women who had breast cancer in the past is linked to a significant increased risk of disease recurrence according to a meta-analysis by researchers from Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy. While great advances have been made in the treatment of breast cancer such as the use of monoclonal antibodies, blocking of oestrogen is associated with several adverse effects which negatively impact on a woman’s quality of life. HRT use is the most effective treatment for symptoms related to a reduced oestrogen levels although it is generally avoided in women with a past history of breast cancer.
In 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. Nevertheless, has been suggested that there is insufficient evidence to contra-indicate HRT in breast cancer survivors.
With some level of uncertainty over whether hormonal replacement therapy 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