Clinicopathological Features Related to the Efficacy of CDK4/6 Inhibitor-Based Treatments in Metastatic Breast Cancer

Abstract

Background: Resistance to endocrine therapy has been a major obstacle in the management of hormone receptor (HR)-positive metastatic breast cancer (MBC). Meanwhile, a number of treatments are available to such patients, and physicians often encounter difficulties in choosing the most appropriate treatments for individual patients. The combination of CDK 4/6 inhibitors (CDKi) and endocrine therapy has now become a standard treatment for HR-positive and human epidermal growth factor receptor 2 (HER2)-negative MBC. However, no predictive markers for CDKi-based treatments have been established. Considering their side effects and the financial burden on patients, identifying such markers is crucial. Methods: Clinicopathological features of 107 patients with HR-positive HER2-negative MBC, who received CDKi-based treatments at our institution were retrospectively investigated. HR status in distant metastatic lesions and immunocompetent cells in peripheral blood were also studied. Results: Progression-free survival (PFS) was significantly shorter in patients whose primary tumour was high grade ( P = 0.016) or high neutrophil-to-lymphocyte ratio (NLR) at baseline ( P = 0.017). Meanwhile, there were no differences in other factors, such as expression levels of hormone receptors. Patients whose metastatic lesions were of low tumour grade or high Ki67 labelling index had longer PFS, and such trends were more obvious than primary lesions. Conclusion: Our data indicate that tumour grade in primary lesion and NLR are potential predictive factors for CDKi-based treatments. Moreover, pathological assessment of metastatic lesions might also be useful.

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

“…Our population is therefore notably homogeneous, that increasing the power. Indeed, other studies were interested in the NLR prognostic factor, but their population was inhomogeneous as they included patients at the localized and metastatic stage ( 39 ), or metastatic patients only and under cdk4/6 inhibitors but all lines combined without information on previous treatments ( 40 , 41 ). In this sense, it is an original study.…”

High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs

“…The platelet-to-lymphocyte ratio (PLR) has also been studied, and for breast cancer patients, both NLR and PLR are now established prognostic markers across all intrinsic subtypes [ 10 , 12 , 13 ]. In relation to therapeutic effect, a high NLR reportedly correlates with poor responsiveness to systemic treatments in breast cancer patients [ 11 , 14 ] and we also previously reported a similar trend in eribulin-based and CDK4/6 inhibitor-based treatments [ 15 , 16 ]. Lymphocyte activity is also recognized as crucial and high lymphocyte counts are associated with better response to chemotherapies in patients with metastatic breast cancer [ 17 – 19 ].…”

An Italian Real-World Study Highlights the Importance of Some Clinicopathological Characteristics Useful in Identifying Metastatic Breast Cancer Patients Resistant to CDK4/6 Inhibitors and Hormone Therapy

“…Shikanai A and colleagues analyzed the clinicopathological features related to the efficacy of CDK4/6 inhibitor-based treatments in metastatic breast cancer in Japan [ 31 ]. They reported that progression-free survival (PFS) was significantly shorter in patients whose primary tumor was high grade ( p = 0.016) or in those with a high neutrophil-to-lymphocyte ratio (NLR) at baseline ( p = 0.017).…”