Table 3.

Local hormonal treatments in breast cancer survivors: summary of studies and their outcomes

Ref.	Yr	n 1	Design	Treatment	Conclusion
Dew et al[178]	2003	69	Retrospective Cohort study	Estriol 0.5 mg cream and pessaries (33); Estradiol 25 μgtablets (n = 33)	VET does not seem to be associated with increased RR of BC
Kendall et al[190]	2005	7	Prospective before-after analysis	Estradiol 25 mg daily for 2 wk	Vaginal estradiol tablet significantly raises systemic estradiol levels. This reverses the estradiol suppression achieved by AIs in women with BC and is contraindicated
Biglia N et al[179]	2010	26	Prospective study	Estriol cream 0.25 mg (n = 10) or estradiol tablets 12.5 microg (n = 8) polycarbophil-based moisturizer 2.5 g (Replens®) (n = 8)	VET is effective in improving symptoms and objective evaluations in BCSs
Pfeifer et al[180]	2011	10	Prospective before-after analysis	0.5 mg vaginal estriol daily for 2 wk	Increase in FHS and LH may indicate systemic estradiol effects
Whiterby et al[201]	2011	21	Phase I/II pilot Before-After study	Testosterone cream daily for 28 d. 300/ 150 μg	Vaginal testosterone was associated with improved signs and symptoms of vaginal atrophy related to AI therapy without increasing estradiol or testosterone levels
Wills et al[49]	2012	24 vs 24	Prospective clinical trial	25 mcg estradiol vaginal tablet or ring vs control	VET treatment increases E2 levels. Should be used with caution
Le Ray et al[187]	2012	13479TAM (n = 10806) or AIs (n = 2673)	Retrospective, nested case-control study	Vaginal cream and tablets containing estrogen	Use of VET is not associated with increase in BC recurrence in those treated with TMX or AI
Dahir et al[202]	2014	13	Pilot before-after study	Testosterone cream daily for 28 d, 300 μg	Improvement in FSFI scores
Donders et al[181]	2014	16	Open label bicentric phase I pharmacokinetic study	0.03 mg Estriol + Lactobacillus	Estriol + Lactobacillusis safe in BCpatients andimprovessymptoms
Melisko et al[204]	2016	69	Randomised non-comparative study	Estradiol ring 7.5 ng vs Testosterone cream at 1% concentration: 1.5 mg/wk	Transient increase in E2 that finally reached normal levels. Meets the primary safety endpoint
Davis et al[203]	2018	44	Double-blind, randomised, placebo-controlled trial	Testosterone cream daily for 26 week/ 300 μg vs placebo	Testosterone improves sexual test items compared to placebo

¹Cases vs control. BC: Breast cancer, BCSs: Breast cancer survivors; TAM: Tamoxifen; AIs: Aromatase inhibitors; VET: Vaginal estrogen treatment; FSFI: Female Sexual Function Index.