This guideline uses the term “breast cancer recurrence” to refer to the occurrence of breast cancer in any location of the body after treatment for an initial breast cancer.
All 45 studies included in the primary systematic review were reviewed for information on breast cancer recurrence. Three studies of menopause hormone therapy reported formal data analyses on breast cancer recurrence, while three studies of other therapies reported cancer occurrence (not necessarily breast cancer recurrence) with no formal analysis.
Two systematic reviews, one of testosterone and another one of tibolone, identified in the supplementary Evidence Review included reporting of breast cancer recurrence as an outcome of interest.
Menopause hormone therapy
There was no level I evidence from systematic reviews regarding the recurrence of breast cancer in women after breast cancer who were administered menopause hormone treatments.
One RCT (with a high risk of bias) in women after breast cancer found that menopause hormone therapy (sequential or continuous combined oestrogen/progestogen) was associated with a significantly higher rate of new breast cancer events compared with no treatment, resulting in the early termination of this study.90 One RCT (with a high risk of bias) of menopause hormone therapy (combined oestradiol/medroxyprogesterone) in women after breast cancer was terminated early due to safety concerns related to breast cancer recurrence.91 One RCT (with a low risk of bias) in women after breast cancer found that tibolone (2.5 mg/d) was associated with a significantly higher rate of new breast cancer events compared with no treatment.34 [ES29]
Three RCTs in a Systematic Review (with a low risk of bias) in postmenopausal women reported that tibolone was associated with a significant reduction in breast cancer occurrence compared to placebo, but no significant difference in breast cancer occurrence compared to menopause hormone therapy. The authors acknowledge that the follow-up duration in these studies may be insufficient to fully assess the risk of breast cancer associated with tibolone.38 [ES67]
Other hormone therapies
Thirty-five RCTs analysed in a Systematic Review (with a low risk of bias) in peri- and postmenopausal women (natural or surgically-induced, with or without a history of breast cancer) did not report the effect of long term use of testosterone. The authors acknowledged that testosterone should be used with caution as the dose, duration, safety and long-term effects have not been established.44 [ES66]