Neue Strategien beim metastasierten, endokrin sensitiven Mammakarzinom

Therapeutic strategies for hormone receptor-positive, human epidermal growth factor receptor-negative (HR+, HER2−) metastatic breast cancer will experience relevant changes in upcoming years due to new endocrine treatment options.

This paper summarizes the current standards and gives an outlook on new strategies and representative agents.

The current work is based on a selective literature research in the PubMed databank on the subject “treatment of metastatic HR+, HER2− breast cancer” from the year 2020 onwards.

Treatment with a CDK4/6 inhibitor in first line remains standard. Among all CDK4/6 inhibitors, only ribociclib showed a clinically relevant and statistically significant overall survival benefit in all first-line trials. Treatment with a CDK4/6 inhibitor beyond progression, particularly with a switch of the CDK4/6 inhibitor and the endocrine therapy backbone, remains limited to individual case decisions. With the use of triplets (CDK4/6 inhibitor, PI3K inhibitor in the case of PI3K mutation, selective estrogen receptor destabilizer [SERD]), the early progression in primary and secondary endocrine resistance seems to be avoidable to a large extent. Oral SERDs will replace fulvestrant. They help to overcome endocrine resistance in the case of an ESR1 mutation but above all, they reduce the “time toxicity” caused by the need of patients’ visits. Capivasertib shows a good improvement in progression-free survival, especially in patients with mutations in the AKT signal transduction pathway, but shows relevant side effects (diarrhea, nausea, hyperglycemia).

Only treatment with a CDK4/6 inhibitor provided an overall survival benefit among all endocrine therapies. Treatment algorithms will change in the future due to the overall survival benefits of antibody–drug conjugates (ADCs) and the use of endocrine triplets.