Work

Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion

Year: 2025

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: IMPORTANCE: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain. OBJECTIVE: The present systematic review, meta-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors. DATA SOURCES: Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality. STUDY SELECTION: All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research. MAIN OUTCOMES AND MEASURES: Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of meta-analysis evidence with definition of current knowledge gaps and future research aims. RESULTS: = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders. CONCLUSIONS AND RELEVANCE: The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, cannot be ruled out when TE is used during AI.

Source: Cancer Treatment Reviews

DOI: 10.1016/j.ctrv.2025.102880