OBJECTIVES: Effectiveness of pre-operative endocrine therapy (PoET) in hormone-positive early-stage breast cancer (BC) patients for additional benefits (reduced cell proliferation and risk of recurrence) is being debated. Hence, we aimed to conduct this systematic review and meta-analysis to provide overview and comprehensive data on the effectiveness of PoET in reducing cancer cell proliferation among hormone positive breast cancer patients.

METHODS: We performed a comprehensive literature search in PubMed^®, Scopus^®, Embase®, The Cochrane Library, ClinicalTrail.gov and Google scholar to identify the literatures published from inception until December 2021 that evaluated the change in Ki67 index following PoET among hormone positive breast cancer patients. Mantel Haenszel random-effect model was used for estimating pooled risk-ratio for required outcomes.

RESULTS: A total of 8 studies (2 pre-post interventional studies and 6 randomized control trails) were included. These included 5610 patients for final analysis. Of them, 5/8 (62.5%) studies evaluated the Ki-67 changes in post-menopausal patients, 1/8 (12.5%) studies evaluated pre-menopausal patients and 2/8 (25%) studies evaluated both in pre- and post-menopausal patients. The duration of PoET ranges from 1-18 weeks and drugs employed were tamoxifen 1-20mg, letrozole 2.5mg, anastrozole 1mg, exemestane 25mg and raloxifene 60mg. Overall, in three studies showed significant reduction in Ki-67 following Tamoxifen therapy (P=0.0002, P=<0.001, P=0.0001). In four studies, compared the change in Ki-67 following different endocrine therapies found statistically significant reduction in Ki-67 level (letrozole vs tamoxifen P=0.0009, anastrozole vs tamoxifen vs anastrozole plus tamoxifen P=0.001, exemestane vs letrozole vs anastrozole P=<0.001, anastrozole vs letrozole P=<0.001) except one study (tamoxifen vs raloxifene P=0.78) indicates less cells proliferation. Meta-analysis shows significant difference in between patients receiving mono tamoxifen vs other mono or combination therapy (p=0.002)

CONCLUSIONS: This review reinforces that PoET has an ability to reduce the proliferation index (Ki67) in early stage of breast cancer.