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

Abstract

Purpose 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.

Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer

“…The rwPFS endpoint measured in this study has also been validated in the Flatiron database 33 . A key strength of this analysis is the inclusion of key variables that can affect treatment selection and survival, including the number of metastatic sites, ECOG performance status, visceral involvement, and the interval from initial breast cancer diagnosis to MBC diagnosis, improving the ability to balance patient cohorts and reduce the risk of confounding 34 , 35 . The opportunity for real-world evidence to be a component in regulatory decision making continues to evolve, and as standards in real-world study design and transparency in analysis and reporting are adhered to there remains an important opportunity to leverage this data for that purpose 36 .…”

Clever-1 positive macrophages in breast cancer

“…CD8 + lymphocytes are cytotoxic cells that engage in tumor killing by inducing cytolysis [ 40 ], which explains their positive effect on prognosis, a finding well in line with previous studies [ 41 – 45 ]. PR negativity associates with a worse prognosis in ER + breast cancer, and with resistance to endocrine treatment [ 46 , 47 ].…”

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

“…Prognostic factors are important in estimating outcomes and identifying the optimal treatment for each patient. Some clinical or histological markers are commonly used and validated in HR+/HER2- mBC such as poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS), higher tumor grade and Ki67 expression, negative progesterone receptor (PR) status, prior therapy, sites and number of metastases (multiple vs single), and shorter time to progression to mBC ( 7 ). The choice of first-line treatment is crucial, as it affects patients’ outcome.…”