TY - JOUR
T1 - The next era of treatment for hormone receptor-positive, HER2-negative advanced breast cancer
T2 - Triplet combination-based endocrine therapies
AU - Cortés, Javier
AU - Im, Seock Ah
AU - Holgado, Esther
AU - Perez-Garcia, Jose M.
AU - Schmid, Peter
AU - Chavez-MacGregor, Mariana
N1 - Funding Information:
Dr. Cortés has received honoraria from Roche, Novartis, Eisai, Celgene, and Pfizer, and has acted as a consulting advisor to Roche, Celgene, AstraZeneca, Cellestia Biotech, and Biothera. Dr. Im reports advisory board member consultation fees from Novartis, Spectrum, and Hanmi outside the submitted work. Dr. Schmid reports personal fees from Pfizer, Boehringer, Bayer, Puma, Eisai, Celgene, and Roche/Genentech. Dr. Chavez-MacGregor reports research support from Novartis and personal fees from Pfizer outside the submitted work. Dr. Holgado and Dr. Perez-Garcia have no conflicts of interest to disclose.
Publisher Copyright:
© 2017 The Authors
PY - 2017/12
Y1 - 2017/12
N2 - Until recently, the standard of care for hormone receptor-positive (HR+) breast cancer was single-agent endocrine therapy, which aims to prevent estrogen receptor signaling. This therapeutic strategy has extended survival without the toxicity associated with chemotherapy, but primary endocrine therapy resistance is common, and secondary resistance develops over time. Adjunct downstream inhibition of the cyclin-dependent kinase (CDK)4/6 pathway, intended to delay and prevent endocrine therapy resistance, has further extended progression-free survival in patients receiving endocrine therapy; however, resistance still eventually develops in these patients. Addition of phosphatidylinositol-3 kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors to combined CDK4/6 and endocrine inhibitor regimens may help prolong CDK4/6 inhibitor sensitivity. Early trials combining CDK4/6 inhibitors, PI3K or mTOR inhibitors, and endocrine therapy have shown encouraging signs of clinical activity. However, further research is needed to help understand the extent of treatment benefit from triplet therapy and where this strategy will fit in the treatment sequence for patients with HR+ breast cancer.
AB - Until recently, the standard of care for hormone receptor-positive (HR+) breast cancer was single-agent endocrine therapy, which aims to prevent estrogen receptor signaling. This therapeutic strategy has extended survival without the toxicity associated with chemotherapy, but primary endocrine therapy resistance is common, and secondary resistance develops over time. Adjunct downstream inhibition of the cyclin-dependent kinase (CDK)4/6 pathway, intended to delay and prevent endocrine therapy resistance, has further extended progression-free survival in patients receiving endocrine therapy; however, resistance still eventually develops in these patients. Addition of phosphatidylinositol-3 kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors to combined CDK4/6 and endocrine inhibitor regimens may help prolong CDK4/6 inhibitor sensitivity. Early trials combining CDK4/6 inhibitors, PI3K or mTOR inhibitors, and endocrine therapy have shown encouraging signs of clinical activity. However, further research is needed to help understand the extent of treatment benefit from triplet therapy and where this strategy will fit in the treatment sequence for patients with HR+ breast cancer.
KW - Advanced breast cancer
KW - Cyclin-dependent kinase 4/6 inhibitor
KW - Endocrine therapy
KW - Hormone receptor-positive
KW - PI3K/mTOR inhibitor
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U2 - 10.1016/j.ctrv.2017.09.011
DO - 10.1016/j.ctrv.2017.09.011
M3 - Review article
C2 - 29100169
AN - SCOPUS:85032488299
SN - 0305-7372
VL - 61
SP - 53
EP - 60
JO - Cancer treatment reviews
JF - Cancer treatment reviews
ER -