TY - JOUR
T1 - Characterization of weaning-induced breast involution in women
T2 - implications for young women’s breast cancer
AU - Jindal, Sonali
AU - Narasimhan, Jayasri
AU - Borges, Virginia F.
AU - Schedin, Pepper
N1 - Funding Information:
Margaret C. Neville for critical review of the manuscript and members of Schedin, Borges, and Coussens labs for intellectual contribution. We are grateful to members of IU Simon Komen Tissue Bank for contributing specimens and to all the women who donated their breast tissue for research purposes. This work was funded by the following grants to V.B. & P.S: NIH/NCI R01#1CA169175, the Willard L. and Ruth P. Eccles Foundation, the Coit Family Foundation, and the Kay Yow Foundation This work is also funded in part through the Oregon Health & Science University School of Medicine Faculty Innovation Funds to P.S. and through the John F. and Patricia Young Connor endowed chair to V.B. We appreciate the contribution to this research from the Tissue Bio banking and Processing Shared Resource of Colorado’s NCI Cancer Center Support Grant P30CA046934 and the OHSU Knight Cancer Institute’s Cancer Center Support Grant P30CA69533.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - In rodents, weaning-induced mammary gland involution supports increased mammary tumor incidence, growth, and progression to metastasis. Further, the protumor attributes of gland involution are COX-2 dependent and mitigated by short-duration non-steroidal anti-inflammatory drugs (NSAIDs), suggesting a potential prevention strategy. However, the transition from lactation to postweaning breast involution has not been rigorously evaluated in healthy women. Here we queried breast biopsies from healthy women (n = 112) obtained at nulliparity, lactation, and multiple postweaning time points using quantitative immunohistochemistry. We found that mammary remodeling programs observed in rodents are mirrored in the human breast. Specifically, lactation associates with the expansion of large, secretory mammary lobules and weaning associates with lobule loss concurrent with epithelial cell death and stromal hallmarks of wound healing, including COX-2 upregulation. Altogether, our data demonstrate that weaning-induced breast involution occurs rapidly, concurrent with protumor-like attributes, and is a potential target for NSAID-based breast cancer prevention.
AB - In rodents, weaning-induced mammary gland involution supports increased mammary tumor incidence, growth, and progression to metastasis. Further, the protumor attributes of gland involution are COX-2 dependent and mitigated by short-duration non-steroidal anti-inflammatory drugs (NSAIDs), suggesting a potential prevention strategy. However, the transition from lactation to postweaning breast involution has not been rigorously evaluated in healthy women. Here we queried breast biopsies from healthy women (n = 112) obtained at nulliparity, lactation, and multiple postweaning time points using quantitative immunohistochemistry. We found that mammary remodeling programs observed in rodents are mirrored in the human breast. Specifically, lactation associates with the expansion of large, secretory mammary lobules and weaning associates with lobule loss concurrent with epithelial cell death and stromal hallmarks of wound healing, including COX-2 upregulation. Altogether, our data demonstrate that weaning-induced breast involution occurs rapidly, concurrent with protumor-like attributes, and is a potential target for NSAID-based breast cancer prevention.
UR - http://www.scopus.com/inward/record.url?scp=85092647908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092647908&partnerID=8YFLogxK
U2 - 10.1038/s41523-020-00196-3
DO - 10.1038/s41523-020-00196-3
M3 - Article
AN - SCOPUS:85092647908
SN - 2374-4677
VL - 6
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 55
ER -