Prognostic Factors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2–) Advanced Breast Cancer: A Systematic Literature Review

Abstract

Gebra Cuyún Carter,1 Maitreyee Mohanty,2 Keri Stenger,1 Claudia Morato Guimaraes,1 Shivaprasad Singuru,3 Pradeep Basa,3 Sheena Singh,3 Vanita Tongbram,2 Sherko Kuemmel,4,5 Valentina Guarneri,6 Sara M Tolaney7 1Eli Lilly and Company, Indianapolis, IN, USA; 2Global Health Economics and Outcomes Research, ICON Plc, New York, NY, USA; 3Global Health Economics and Outcomes Research, ICON Plc, Bangalore, Karnataka, India; 4Interdisciplinary Breast Unit, Kliniken Essen-Mitte (KEM), Essen, Germany; 5Charité – Universitätsmedizin Berlin, Department of Gynecology with Breast Center, Berlin, Germany; 6Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, PD, Italy; Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, PD, Italy; 7Dana-Farber Cancer Institute, Brookline, MA, 02215, USACorrespondence: Maitreyee MohantyGlobal Health Economics and Outcomes Research, ICON Plc., New York, NY, USAEmail [email protected]: Advanced breast cancer is a heterogeneous disease with several well-defined subtypes, among which, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) is most prevalent. Determination of HR and HER2 status influences prognosis and, thus, disease management. Although literature on these prognostic factors exist, especially in the early breast cancer setting, it remains unclear to what extent these factors can guide clinical decision-making in the advanced disease setting. Therefore, we sought to identify the strength and consistency of evidence for prognostic factors in patients with HR+/HER2– advanced breast cancer.Methods: A systematic literature review (SLR) of the major electronic databases was conducted in November 2018 for primary research studies published since 2010. Endpoints of interest were tumor response, progression-free survival (PFS), overall survival (OS), and breast cancer-specific survival (BCSS).Results: Seventy-nine studies were included wherein all patients were diagnosed with advanced breast cancer and ≥ 50% of the population were HR+/HER2–. OS was the most commonly assessed endpoint (n=67) followed by PFS (n=33), BCSS (n=5) and tumor response (n=3). The prognostic factors with strongest evidence of association with worse OS were negative progesterone receptor status, higher tumor grade, higher circulating tumor cell (CTC) count and higher Ki67 level, number of metastatic sites (eg multiple vs single) and sites of metastases (eg presence of liver metastases vs absence), shorter time to recurrence or progression to advanced breast cancer, 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). The prognostic factors that had strongest evidence of association with PFS included CTC count, number and sites of metastases, and absence of prior therapy or higher lines of therapy in the early or metastatic setting. The directionality of association was consistent for all prognostic factors except between lymph node and OS, and de novo metastatic breast cancer and PFS.Conclusion: Multiple disease, treatment, and patient-related prognostic factors impact survival, particularly OS, in patients with HR+/HER2– advanced breast cancer. Treatment outcomes can vary considerably due to these factors. Understanding poorer prognostic factors for patients can result in improved clinical decision-making.Keywords: advanced breast cancer, prognostic factors, survival

Keywords

• advanced breast cancer
• prognostic factors
• survival