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or across disparate stages of breast cancer development, including metastasis. Indeed, TMM selection may
itself be subject to evolutionary dynamic forces. In addition, the plasticity inherent in TMM identity has far-
reaching prognostic and therapeutic implications. Tumors driven by distinct TMMs may show sensitivity
or resistance to specific treatments, which has substantial impact on patient survival. Moreover, different
subpopulations within a single tumor (e.g., stem vs. non-stem cells) may be reliant upon unique TMMs.
Such TMM heterogeneity may beget residual, resistant clones that underlie disease recurrence. In the future,
gaining a deeper understanding of telomeres and the pathways controlled by the telomere machinery will
provide immense insight into the origin, progression, and eradication of one of the world’s deadliest cancers.

DECLARATIONS
Acknowledgments
Members of the Schiemann Laboratory are thanked for critical comments and reading of the manuscript.

Authors’ contributions
Conception and study design: Robinson NJ, Schiemann WP
Drafted and revised the manuscript: Robinson NJ, Taylor DJ, Schiemann WP

Availability of data and materials
Not applicable.

Financial support and sponsorship
Research support was provided in part by the National Institutes of Health (CA236273) to Schiemann WP,
(CA186571) to Taylor DJ; and (T32 GM007250 and F30 CA213892) to Robinson NJ. Additional support
was graciously provided by the METAvivor Foundation (Schiemann WP), and by pilot funding from the
Case Comprehensive Cancer Center’s Research Innovation Fund, which is supported by the Case Council
and Friends of the Case Comprehensive Cancer Center (Schiemann WP), and from the Case Clinical &
Translational Science Collaborative (Schiemann WP). Finally, Taylor DJ is also supported by the American
Cancer Society (RSG-13-211-01-DMC).

Conflicts of interest
All authors declare that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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