Translational RelevancePre-/perimenopausal patients with hormone-receptor positive (HR+)/human epithelial growth factor 2 negative (HER2-) advanced breast cancer (ABC) typically have a poorer prognosis and are under-represented in clinical trials. MONALEESA-7 is a phase 3 trial that studied ribociclib plus endocrine therapy (ET) versus placebo plus ET and dedicated specifically to peri-/premenopausal patients with HR+/HER2-ABC. The final protocol-specified overall survival (OS) analysis of MONALEESA-7 demonstrated a statistically significant OS benefit with ribociclib, however, outcomes can change over time, requiring prolonged observation to account for this disease's long natural history.An exploratory OS analysis of MONALEESA-7 with an extended follow-up (median, 53.5 months) was conducted revealing a median OS of 58.7 months in the ribociclib group versus 48.0 months in the placebo group (hazard ratio, 0.76; 95% CI, 0.61-0.96) with no new safety signals observed. These results show that ribociclib + ET continued to demonstrate OS benefit in pre-/perimenopausal patients long term.Research.
Despite decades of research, ovarian cancer is still associated with unacceptably high mortality rates, which must be addressed by novel therapeutic approaches. One avenue through which this may be achieved is targeting of tumor-initiating ‘Cancer Stem Cells’ (CSCs). CSCs are sufficient to generate primary and recurrent disease through extensive rounds of asymmetric division, which maintain the CSC pool while producing the tissues that form the bulk of the tumor. CSCs thrive in the harsh tumor niche, are generally refractory to therapeutic intervention and closely-linked to the Epithelial-Mesenchymal Transition process, which facilitates invasion and metastasis. While it is well-accepted that CSC-targeting must be assessed as a novel therapeutic avenue, few ovarian CSC models have been developed due to perceived and actual difficulties associated with the process of ‘CSC Discovery’. In this article we review contemporary approaches to CSC Discovery and argue that this process should start with an understanding of the specific challenges associated with clinical intervention, laying the pipeline backwards towards CSC Discovery. Such an approach would expedite the bridging of the gap between laboratory isolation and clinical targeting of ovarian CSCs.
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