The heterogeneity of
hormone receptor (HR)-positive, HER2-negative early breast
cancers reinforces the importance of individualized, risk-adapted treatment approaches. Numerous factors contribute to the risk for recurrence, including clinical
tumor features, individual
biomarkers, and genomic risk. Current standard approaches for patients with HR-positive, HER2-negative, early stage disease focus on endocrine
therapy and
chemotherapy. The specific treatment regimen and duration of adjuvant
therapy should be selected based on accurate risk assessment, tolerability of available
therapies, and consideration for patient preferences. For patients with high-risk features, such as highly proliferative
tumors, large
tumor size, and significant nodal involvement, the risk for recurrence remains clinically significant despite appropriate adjuvant treatment with current standards of care. This has driven investigation into novel treatment approaches, including the addition of
cyclin-dependent kinase 4 and 6 inhibitors to adjuvant endocrine
therapy.
Cyclin-dependent kinase 4 and 6 inhibition has demonstrated significant efficacy in patients with high-risk, HR-positive, HER2-negative, nonmetastatic
breast cancer and now offers a new strategy to greatly improve outcomes in this difficult to treat patient population.; LAY SUMMARY:
Hormone receptor (HR)-positive, HER2-negative early breast
cancers are highly diverse and need to be managed differently for individual patients. The use of adjuvant endocrine
therapy and
chemotherapy should be driven by a patient's risk for recurrence, preferences, and risk for side effects. Patients with high-risk
tumors have a persistently elevated risk for recurrence despite current standards of care. Emerging
cyclin-dependent kinase 4 and 6 inhibitors are highly effective when added to endocrine
therapy in high-risk, HR-positive early
breast cancer and have the potential to improve patient outcomes in this difficult to treat patient population.