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recurrent breast cancer in Japan: a role for mammalian target of rapamycin inhibitors?

Takahiro Nakayama

Fumie Fujisawa

Takahiro Nakayama

*Author for correspondence: Tel.: +81 6 6945 1181; Fax: +81 6 6945 1900;

E-mail Address: taqnakayama@gmail.com

https://orcid.org/0000-0002-3713-1624

Breast & Endocrine Surgery, Osaka International Cancer Institute, Osaka, Japan

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Fumie Fujisawa

https://orcid.org/0000-0001-8436-9072

Medical Oncology, Osaka International Cancer Institute, Osaka, Japan

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Published Online:2 Jul 2020https://doi.org/10.2217/fon-2020-0326

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Abstract

Despite advances in the treatment of hormone receptor-positive, HER2- metastatic breast cancer, the disease is rarely curable. In this review, we focus on the use of CDK4/6 inhibitors, examining clinical experience and the mechanisms underlying the development of resistance, and evaluating treatment options after failure to respond to CDK4/6 inhibitors. Current basic research supports the use of mammalian target of rapamycin inhibitors after CDK4/6 inhibitor failure; however, more data are needed, particularly regarding treatment sequencing. Real-world data studies may help to fill the current knowledge gap, particularly where large-scale randomized controlled studies are not feasible.

Lay abstract

This review highlights the importance of CDK4/6 inhibitors in the treatment of postmenopausal, hormone receptor-positive (HR+), HER2- metastatic breast cancer (MBC), and provides published evidence to suggest mammalian target of rapamycin inhibitors as a therapeutic option for patients who do not respond to CDK4/6 inhibitors. Ideally, clinicians would be able to offer optimal treatment sequences to avoid CDK4/6 inhibitor resistance development and recommend therapeutic options for patients who have developed resistance. This review identifies current issues with the treatment of postmenopausal HR+, HER2- metastatic breast cancer and offers suggestions for moving toward best practices.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 16, No. 24

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History

Received 9 April 2020

Accepted 28 May 2020

Published online 2 July 2020

Published in print August 2020

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Keywords

Author contributions

T Nakayama was responsible for the conception/design of the work, analysis/interpretation of the information and drafting the manuscript. F Fujisawa was responsible for the conception/design of the work, analysis/interpretation of the information and critically revising the manuscript for important intellectual content. Both authors provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Financial & competing interests disclosure

This paper was funded by Novartis Pharma K.K. T Nakayama reports receiving honoraria from Chugai, AstraZeneca, Novartis, Eli Lilly, Pfizer, Ono, Taiho, and Takeda. F Fujisawa reports receiving honoraria from Chugai, AstraZeneca, Novartis, Pfizer, and Eisai. No grants, equipment, or drugs were provided to the authors for research support related to this review article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors thank SA Mitchell of Edanz Medical Writing for providing medical writing support, which was funded by Novartis Pharma K.K. through EMC K.K. in accordance with Good Publication Practice guidelines (www.ismpp.org/gpp3).

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. As the data analysis was retrospective, patient informed consent was not required.

Data sharing statement

Data relating to the retrospective analysis will be provided by the corresponding author, upon reasonable request.

Open access

This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

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