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[131]
although the pharmacodynamic analysis confirmed the target inhibition in the entinostat-treated cohort .
Nevertheless, epigenetic modifiers open a new field of research in treating HR-positive breast cancer that
will certainly gain importance in the future. Furthermore, preclinical data provide evidence that combining
[134]
entinostat with palbociclib enhances the antitumoral activity of both drugs . Further clinical studies on
this novel and promising substance are still pending.

CONCLUSION
Endocrine therapeutic strategies are currently being improved and expanded by adding molecularly-
targeted substances. These play an increasingly important role in managing advanced hormone receptor-
positive breast cancer, particularly given the central problem of resistance to endocrine therapy. The search
for biomarkers must be intensively pursued to individualize cancer therapies further. CDK4/6 inhibitors, in
addition to endocrine therapy, have already become the standard of care in the first-line treatment of HR-
positive advanced breast cancer. However, several novel promising substances (e.g., oral SERDs or PI3K
inhibitors) are also being investigated in clinical trials, so an expansion of therapy options can be expected
shortly. Given the rapid scientific progress, knowledge and management of adverse events are critical, as the
new targeted agents are associated with side effects that differ significantly from endocrine therapy alone.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Droste A, Schmidt M

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Marcus Schmidt has received personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD,
Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen. His institution has received
research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos,
Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent
for EP 2951317 B1 issued. Annika Droste reports no conflict of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2023.

REFERENCES
1. Fitzmaurice C, Allen C, Barber RM, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived
with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of
disease study. JAMA Oncol 2017;3:524-48. DOI PubMed PMC