Abstract P3-08-40: Prognostic factors associated with clinical outcomes in HR+, HER2- advanced breast cancer: Systematic literature review
Authors: Carter Gebra C , Stenger Keri , Mohanty Maitreyee , Chong Amy L , Basa Pradeep , Singuru Shivaprasad , Singh Sheena , Tongbram Vanita , Kümmel Sherko , Guarneri Valentina , Tolaney Sara M 
Published: March 2020

Background Advanced breast cancer (ABC) is a heterogeneous disease with several well-defined subtypes, among which, HR+, HER2- is the most prevalent. While clinical factors and genomic signatures have clear prognostic significance in the early breast cancer setting, this is less clear in the advanced disease setting. The aim of this systematic literature review was to identify the strength and consistency of evidence for prognostic factors in HR+, HER2-, ABC patients. Methods A comprehensive search was conducted of the major electronic databases (MEDLINE, EMBASE and Cochrane Controlled Register of Trials) in November 2018 for primary research clinical studies published since 2010 in HR+, HER2- ABC patients. Endpoints of interest were tumor response, progression-free survival (PFS), overall survival (OS), and breast-cancer specific survival (BCSS). Studies were screened by two independent reviewers for eligibility. Results Seventy-nine studies (72 full-text publications and 7 conference abstracts) were included wherein all patients were diagnosed with ABC and ≥50% of the population were HR+, HER2-. The majority were observational studies (n=71). Among the four endpoints, OS was the most commonly (n=67) assessed. Negative progesterone receptor (PR) status, higher tumor grade, higher CTC count, higher Ki67 level, number of metastatic sites (multiple vs. single) and sites of metastases (e.g., presence of liver metastases vs. absence), patients with relapsed BC compared with de novo metastatic BC, shorter time to recurrence or progression to ABC, poor performance status, prior therapy attributes in the early or metastatic setting (type of therapy, treatment line, response of prior therapy), and race (black vs. white) were consistently (&gt;50% of studies found significant association) associated with worse OS; the relationship was inconsistent for tumor size, histological type (lobular vs. ductal), lymph node involvement and age. Directionality of relationship was consistent for all factors except lymph node involvement. Strength of association with OS was moderate [hazard ratio (HR) between 1.5-2.9] for PR status, tumor grade, CTC count, and Ki67 level, number and site (e.g., bone, liver, lung) of metastases, time to recurrence or progression to ABC, performance status, prior therapy attributes, and weak (HR&lt;1.5) for de novo metastatic BC and race. Heterogeneity was observed across the studies in the composition of the patient population, definition and categorization for a few prognostic factors (e.g., number and sites of metastases, prior therapy, age). Similar results from fewer number of studies were observed for tumor response, PFS, BCSS. Conclusions Based on consistency and strength of the data PR status, tumor grade, CTC count, number and sites metastases, time to recurrence or progression to ABC, performance status, and prior therapy attributes were identified as the prognostic factors that had the strongest evidence. The application of these factors may be able to inform future research and clinical decision-making to improve outcomes in patients with HR+/HER2- ABC.

Association between prognostic factors and overall survivalPrognostic factor Total no. of studies that assessed associationTotal no. of studies reporting significant association No. studies with significant multivariate analysis PR status1085Tumor Grade211411CTC count1097Ki67542No. of metastatic sites262313Site of metastasis332117De novo metastatic BC543Tumor size1255Lymph node1141Histological type 511Time to disease recurrence or progression18138Performance status14118Prior therapy352720Age371713Race1376

Citation Format: Gebra C Carter, Keri Stenger, Maitreyee Mohanty, Amy L Chong, Pradeep Basa, Shivaprasad Singuru, Sheena Singh, Vanita Tongbram, Sherko Kümmel, Valentina Guarneri, Sara M Tolaney. Prognostic factors associated with clinical outcomes in HR+, HER2- advanced breast cancer: Systematic literature review [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-40.