Supplementary Material for: The Prognostic Significance of Ki-67 Expression in Breast Cancers Developing Malignant Effusions

Purpose: To investigate the prognostic significance of Ki-67 in breast cancer patients developing malignant effusions. Methods: In this retrospective study, 76 breast cancer patients developing a malignant effusion were enrolled. The Ki-67 immunohistochemistry (IHC) findings from both initial tissue and paired metastatic effusion samples of these patients were grouped into the following three categories: ≤5, 6-29, and ≥30%. Results: Triple negative breast cancer (TNBC) showed higher Ki-67 levels at both initial diagnosis (p<0.001) and malignant effusion samples (p=0.015), compared to the non-TNBC phenotypes at the same tumor evolution phases, respectively. A Ki-67≥30% at initial diagnosis was associated with a shorter overall survival (p=0.031; long-rank test), in addition to an earlier development of a malignant effusion (p<0.001; long-rank test). A Ki-67≤5% at malignant effusion cell block samples was associated with a longer post-effusion survival (p=0.015; long-rank test). Lastly, a Ki-67 index≤5% at the effusion samples showed a significantly lower risk of mortality following the development of malignant effusions (HR: 0.355 (0.150 - 0.842; p=0.019)), after being adjusted for the intrinsic subtype covariate (TNBC vs non-TNBC). Conclusion: Estimating the Ki-67 IHC expression in malignant effusion cytology samples may have a prognostic significance, when evaluating patients with metastatic breast cancer. However, larger-scale prospective studies would be necessary to provide more evidence on this topic.