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Page 2 of 4 Schiemann. J Cancer Metastasis Treat 2020;6:3 I http://dx.doi.org/10.20517/2394-4722.2020.01
[12]
[13]
[11]
metastatic cascade , as well as eloquent analyses of how fluidity and plasticity within the hierarchy of
normal and malignant stems cells drives breast cancer development and metastatic progression. Similarly,
[14]
Robinson et al. provide an elegant perspective on how alternations in telomere maintenance mechanisms
influence the metastatic evolution of breast cancer stem cells. Likewise, thoughtful discussions on the
regulation of epithelial-mesenchymal transition (EMT) programs and carcinoma plasticity also extend into
[15]
new arenas of: (1) epigenetic modification of histones by lysine-specific demethylase (LSD1 or KDM1A );
(2) spatiotemporal control of the translatome coupled to EMT by aberrant expression and activation of
[16]
hnRNP E1 ; and (3) mRNA splicing factors and their essential contribution to the acquisition of EMT
[17]
[18]
and metastatic phenotypes . Along these lines, Maisel and Schroeder present an intriguing and
comprehensive discourse on how defects in retrograde trafficking of cytokine and growth factor receptors
contribute to the acquisition of metastatic phenotypes in breast cancer.

Science and medicine currently lack the knowledge to understand how disseminated breast cancers escape
clinical detection by remaining dormant for years before reemerging as chemoresistant and incurable
secondary tumors [19,20] . Indeed, the mysteries of metastatic dormancy have been identified as one of the
[21]
ten most critical research gaps and translational priorities needed to be solved to alleviate breast cancer .
Herein, the paradoxical role of autophagy in both suppressing and promoting breast cancer development
and metastatic progression is discussed, particularly its importance in maintaining dormancy-associated
[22]
[23]
phenotypes in disseminated breast cancer cells . Gooding et al. highlight the far-reaching impact
of the noncoding genome and the long noncoding RNA BORG in regulating breast cancer metastasis,
chemoresistance, and disease recurrence during metastatic dormancy. Not to be forgotten are the
essential functions of the tumor microenvironment in regulating breast cancer biology and metastatic
[24]
progression . Indeed, the therapeutic potential of disrupting breast cancer cell communication with
[25]
stromal factors and cryptic peptides is presented , as are intriguing discussions of how: (1) involution
in the postpartum mammary gland engenders a pro-metastatic microenvironment reminiscent of those
[26]
found in their tumorigenic counterparts ; and (2) stress and inflammatory signals disrupt neuronal
[27]
circuitry, thereby contributing to brain metastasis by breast cancers .
This Special Issue also considers the translational and clinical aspects of therapeutic targeting metastatic
[28]
breast cancers. Indeed, Kamal et al. present a comprehensive review comparing active vs. passive
[29]
treatment strategies to alleviate breast cancer metastasis to the brain, while dos Santos et al. offer an
equally far-reaching review on the molecular mechanisms underlying photodynamic therapy and its
potential to treat metastatic disease. Additionally, the clinical utility of monitoring circulating tumor
[30]
cellsas a measure of disease progression and therapeutic effectiveness is also discussed .

Finally, it is our hope that these timely and topical reviews will prove to be intellectually stimulating and
highly thought-provoking. Likewise, we invite you to explore the 13 original articles and 3 case reports,
which dovetail topically with the aforementioned reviews.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
CA236273.