Cancer is a leading cause of death globally, claiming almost 10 million deaths in 2020.1 Breast cancer is one of the most common cancers in women, with nearly 2.3 million new breast cancer diagnoses in 2020 worldwide.1 Gene-expression profiling has identified distinct subtypes of cancer, among which there are subpopulations expressing specific markers.2 According to the National Institutes of Health (NIH), hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) is the most prevalent breast cancer.3 Cyclin-dependent kinase 4 and 6 (CDK4/6) are good drug targets for cancer, owing to their role in cell cycle progression.4 Ribociclib is one of the 3 inhibitors of CDK4/6 approved in combination with fulvestrant for treating HR+/HER2- advanced breast cancers in adults, based on a series of phase 3 clinical trials called MONALEESA, which tested ribociclib along with different drug partners in HR+/HER2- cancer patients.4-7 The MONALEESA-2 study showed that progression-free survival (PFS) was significantly longer with first-line ribociclib + letrozole than with placebo + letrozole.7 The MONALEESA-7 trial also showed significantly longer median overall survival (mOS) in ribociclib in combination with the endocrine therapy (ET) vs. the placebo arm in postmenopausal HR+/HER2- cancer patients.6 Similarly, the primary MONALEESA-3 trial and its subsequent analysis Demonstrated that ribociclib + fulvestrant had significant OS benefit as compared with placebo in HR+/HER2- patients advanced breast cancer patients.5,6 In a recently held European Society of Medical Oncology (ESMO) Breast Cancer Congress, Neven, et al. presented an updated exploratory mOS analysis result with the longest follow-up of the MONALEESA 3 study to date.8