Abstract P5-13-02: Neoadjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer: Comprehensive systematic review and meta-analysis
Authors: Spring L , Gupta A , Reynolds KL , Gadd MA , Isakoff SJ , Ellisen LW , Moy B , Bardia A 
Published: May 2016

Background: ER positive tumors are generally highly responsive to endocrine treatment. However, the specific indications for neoadjuvant endocrine therapy, both as monotherapy and in combination with other therapies, in early breast cancer remain unclear. We conducted a comprehensive systematic review and meta-analysis to evaluate the impact of neoadjuvant endocrine therapy on response rate (RR), based on clinical response or imaging, and pathological complete response rate (pCR) for ER positive breast cancer.

Methods: Based on QUORUM guidelines, a librarian-led search of PubMed, Ovid, and EMBASE was performed to identify eligible trials published prior to May 15, 2015. Inclusion criteria were prospective, randomized neoadjuvant trials that had at least one arm with neoadjuvant endocrine therapy and reported RR. Pooled odds ratios (ORs), 95% confidence intervals (CI), and p values were estimated for endpoints using the fixed and random effects statistical model.

Results: We identified 477 citations initially with 277 remaining after duplications were removed. Twenty trials ultimately met inclusion criteria, with a total sample size of 3,493. The majority of studies (90%) focused on post-menopausal women and compared chemotherapy to endocrine therapy, different durations and types of endocrine therapies, or combinations with growth factor pathway inhibitors. Overall, as compared to chemotherapy, neoadjuvant endocrine therapy had a similar clinical RR (OR 0.93, CI: 0.43-2.02, p = 0.85) and radiological RR (OR 0.73, CI: 0.48-1.09, p = 0.12), but lower rate of toxicity (febrile neutropenia, mucositis). Aromatase inhibitors were associated with significantly higher clinical RR (OR 1.69, CI: 1.36-2.10, p = &lt;0.01) and radiological RR (OR 1.49, CI: 1.18-1.89, p = &lt;0.01), as compared to tamoxifen. Dual combination therapy with growth factor pathway inhibitors (n = 4) was also associated with higher radiological RR (OR 1.59, CI: 1.04-2.438, p = 0.03), but not clinical RR (OR 0.76, CI: 0.541.07-1.07, p = 0.11), as compared to endocrine therapy alone. The incidence of pCR in any arm was low overall (&lt;10%) with resultant low numbers not suitable for inter-group comparisons.

Conclusion: Neoadjuvant endocrine therapy is associated with similar response rates as neoadjuvant chemotherapy but with lower toxicity, and neoadjuvant AIs are superior to tamoxifen for ER-positive tumors. Compared to endocrine monotherapy, dual combination therapy may have superior response rates by imaging, but the low number of trials limits strong conclusions. Additional studies and more predictive biomarkers are needed to personalize the optimal neoadjuvant endocrine combination for an individual patient with ER positive breast cancer.

Citation Format: Spring L, Gupta A, Reynolds KL, Gadd MA, Isakoff SJ, Ellisen LW, Moy B, Bardia A. Neoadjuvant endocrine therapy for estrogen receptor (ER) positive breast cancer: Comprehensive systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-13-02.