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Wallace et al. J Cancer Metastasis Treat 2019;5:9 Journal of Cancer
DOI: 10.20517/2394-4722.2019.01 Metastasis and Treatment

Review Open Access

Studies of postpartum mammary gland involution
reveal novel pro-metastatic mechanisms

Taylor R. Wallace , Sarah E. Tarullo , Lyndsey S. Crump , Traci R. Lyons 1,2,3,4
1,2
1,2
1,2
1 Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045,
USA.
2 Young Women’s Breast Cancer Translational Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045,
USA.
3 University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
4 University of Colorado Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora,
CO 80045, USA.

Correspondence to: Dr. Traci R. Lyons, Department of Medicine, Division of Medical Oncology, University of Colorado Asnchutz
Medical Campus, 12801 East 17th Avenue, Aurora, CO 80045, USA. E-mail: traci.lyons@ucdenver.edu

How to cite this article: Wallace TR, Tarullo SE, Crump LS, Lyons TR. Studies of postpartum mammary gland involution reveal
novel pro-metastatic mechanisms. J Cancer Metastasis Treat 2019;5:9. http://dx.doi.org/10.20517/2394-4722.2019.01
Received: 1 Jan 2019 First Decision: 15 Jan 2019 Revised: 23 Jan 2019 Accepted: 24 Jan 2019 Published: 19 Feb 2019

Science Editor: William P. Schiemann Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Postpartum involution is the process by which the lactating mammary gland returns to the pre-pregnant state after
weaning. Expression of tumor-promotional collagen, upregulation of matrix metalloproteinases, infiltration of M2
macrophages, and remodeling of blood and lymphatic vasculature are all characteristics shared by the involuting
mammary gland and breast tumor microenvironment. The tumor promotional nature of the involuting mammary
gland is perhaps best evidenced by cases of postpartum breast cancer (PPBC), or those cases diagnosed within
10 years of most recent childbirth. Women with PPBC experience more aggressive disease and higher risk of
metastasis than nulliparous patients and those diagnosed outside the postpartum window. Semaphorin 7a
(SEMA7A), cyclooxygenase-2 (COX-2), and collagen are all expressed in the involuting mammary gland and,
together, predict for decreased metastasis free survival in breast cancer. Studies investigating the role of these
proteins in involution have been important for understanding their contributions to PPBC. Postpartum involution
thus represents a valuable model for the identification of novel molecular drivers of PPBC and classical cancer
hallmarks. In this review, we will highlight the similarities between involution and cancer in the mammary gland,
and further define the contribution of SEMA7A/COX-2/collagen interplay to postpartum involution and breast
tumor progression and metastasis.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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