Ahmet N. Sanli1, Kadri Altundag2
1Department of General Surgery, Silivri State Hospital, Istanbul, Turkey.
2MKA Breast Cancer Clinic, Tepe Prime, Ankara, Turkey.
Abstract
Dear Editor,
Breast cancer is the most common cancer in women worldwide. Understanding the biology of this tumor is a prerequisite for selecting an appropriate treatment. Cell cycle alterations are seen in many cancers, such as breast cancer. Newly popular targeted agents in breast cancer are cyclin-dependent kinase inhibitors (CDKIs) (palbociclib, ribociclib, abemaciclib) which are agents inhibiting the function of cyclin-dependent kinases (CDKs) [1]. On October 12th 2021, the United States Food and Drug Administration (FDA) approved abemaciclib in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptorpositive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test. A pivotal adjuvant trial concluded that abemaciclib + endocrine therapy significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile [2]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (p<0.0001) and distant relapse-free survival (DRFS) (p<0.0001) benefit was maintained. However, median follow-up time is still quite short for a study of ER+ adjuvant therapy, where the majority of recurrences and deaths occur after 5 years in many studies. Furthermore, this class of cyclin-dependent kinase 4 and 6 is likely cytostatic, rather than cytocidal. It means that it blocks cell proliferation rather than leading to cell senescence and apoptosis. Overall survival was a secondary outcome measure for the monarchE study [2] . This survival information was not included in the recent study, due to immaturity of the data. Whether the survival curves for combination therapy will come together with those for endocrine therapy alone once patients stop taking the drug is still common concern and needs to be investigated.
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