Current Landscape of Targeted Therapies for Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer

Frontiers in Oncology
Tarah J BallingerValerie M Jansen

Abstract

The majority of deaths from MBC are in patients with hormone receptor (HR) positive, HER2 negative disease. Endocrine therapy (ET) remains the backbone of treatment in these cases, improving survival and quality of life. However, treatment can lose effectiveness due to primary or acquired endocrine resistance. Analysis of mechanisms of ET resistance has led to the development of a new generation of targeted therapies for advanced breast cancer. In addition to anti-estrogen therapy with selective estrogen receptor modulators, aromatase inhibitors, and/or selective estrogen receptor degraders, combinations with cyclin dependent kinase (CDK) 4/6 inhibitors have led to substantial progression free survival (PFS) improvements in the first and second line settings. While the PI3K/AKT/mTOR pathway is known to be an important growth pathway in HR positive breast cancer, PI3K inhibitors have been disappointing due to modest effect sizes and significant toxicity. The mTOR inhibitor everolimus significantly improves progression free survival when added to ET, and recent studies have improved supportive care allowing less toxicity. While these combination targeted therapies improve outcomes and often delay initiation of chemotherapy, long ...Continue Reading

References

Jul 1, 1999·Genes & Development·C J Sherr, J M Roberts
Nov 15, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J BonneterreM von Euler
Feb 24, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J G KlijnUNKNOWN Combined Hormone Agents Trialists' Group and the European Organization for Research and Treatment of Cancer
Dec 9, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Linda A deGraffenriedManuel Hidalgo
Oct 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xiaojiang CuiAdrian V Lee
Jul 12, 2007·Nature Clinical Practice. Oncology·Giuseppe Curigliano, Aron Goldhirsch
Aug 19, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·H S Rugo
Dec 7, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sara Lopez-Tarruella, Rachel Schiff
Dec 7, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jill BaylissDorraya El-Ashry
Nov 18, 2008·Cancer Treatment Reviews·Alex S StrimpakosKostas N Syrigos
Aug 25, 2009·Nature Reviews. Cancer·Elizabeth A Musgrove, Robert L Sutherland
Sep 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Angelo Di LeoMiguel Martin
Oct 5, 2010·Annual Review of Medicine·C Kent Osborne, Rachel Schiff
Dec 14, 2011·The New England Journal of Medicine·José BaselgaGabriel N Hortobagyi
Jul 4, 2012·Cell Cycle·A Kathleen McClendonErik S Knudsen
Aug 3, 2012·The New England Journal of Medicine·Rita S MehtaGabriel N Hortobagyi
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Nov 16, 2013·Virchows Archiv : an International Journal of Pathology·Lucia Veronica CuorvoMattia Barbareschi
Dec 10, 2013·Journal of the National Cancer Institute·Angelo Di LeoMiguel Martin
May 21, 2014·Oncology Reports·Rubí Viedma-RodríguezDiego Arenas-Aranda
Sep 19, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M PiccartJ Baselga
Nov 2, 2014·Oncology Letters·Paul ZarogoulidisKonstantinos Zarogoulidis
Dec 3, 2014·Biochimica Et Biophysica Acta·Kai XuWenyi Wei
Dec 3, 2014·Clinical Breast Cancer·John F R RobertsonJulia M W Gee
Aug 8, 2015·Polish Journal of Pathology : Official Journal of the Polish Society of Pathologists·Agnieszka AdamczykJerzy Jakubowicz
Oct 22, 2015·The New England Journal of Medicine·Nicholas C TurnerMassimo Cristofanilli

❮ Previous
Next ❯

Citations

Jan 10, 2019·Marine Drugs·Geert van WeeldenJohanna M A Pijnenborg
Dec 18, 2018·Oncotarget·Meenakshi AnuragSvasti Haricharan
Jan 11, 2019·BioMed Research International·Youcef Derbal
Mar 19, 2020·International Journal of Molecular Sciences·Lei DingQinghua Cui
Feb 6, 2020·Endocrine-related Cancer·Phungern KhongthongJoanne Edwards
Dec 7, 2018·International Journal of Molecular Sciences·Joseph Antoine Salvator FabreArmand Bensussan
Mar 2, 2021·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·Michael CiarametaroRobert Dubois
Jul 16, 2021·Toxicon : Official Journal of the International Society on Toxinology·Cristina Ferreira AlmeidaNatércia Teixeira
Aug 13, 2021·Breast Cancer Research and Treatment·Mariam F EskanderSamilia Obeng-Gyasi
Aug 23, 2021·Progress in Biophysics and Molecular Biology·Josephine WolfElizabeth M O'Day
Sep 14, 2021·Breast Cancer Research and Treatment·Jason A MouabbiMothaffar F Rimawi

❮ Previous
Next ❯

Methods Mentioned

BETA
ESR

Clinical Trials Mentioned

NCT02376985
NCT01610284
NCT01633060
NCT02115282
NCT02632045
NCT03147287
NCT02732119

Software Mentioned

MONALESSA
BALLET
TRINITI
MANTA

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Related Papers

The Breast : Official Journal of the European Society of Mastology
Domen RibnikarFatima Cardoso
Current Opinion in Obstetrics & Gynecology
Parvin F Peddi
Expert Opinion on Drug Metabolism & Toxicology
Joan Rou-En Choo, Soo-Chin Lee
© 2022 Meta ULC. All rights reserved