Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.
Background: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of...
| Published in: | Breast Cancer Research Vol. 21; no. 1 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | research Journal Article |
| Published: |
BioMed Central
7/17/2019
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137558508&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137558508 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 7/17/2019 vid: 21 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 137558508 137558508 NLM31315645 137558508 10.1186/s13058-019-1163-7 NLM31315645 137558508 ppct: 1 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer. aug: au: Basree, Mustafa M. Shinde, Neelam Koivisto, Christopher Cuitino, Maria Kladney, Raleigh Zhang, Jianying Stephens, Julie Palettas, Marilly Zhang, Allen Kim, Hee Kyung Acero-Bedoya, Santiago Trimboli, Anthony Stover, Daniel G. Ludwig, Thomas Ganju, Ramesh Weng, Daniel Shields, Peter Freudenheim, Jo Leone, Gustavo W. Sizemore, Gina M. affil: The Comprehensive Cancer Center, College of Medicine, The Ohio State University, 460 West 12th Avenue, 43210, Columbus, OH, USA sug: subj: Breast Neoplasms Metabolism Inflammation Metabolism Signal Transduction Estrogens Metabolism Breast Feeding Breast Neoplasms Etiology Inflammation Complications Estrogens Adverse Effects Models, Biological Mice Immunohistochemistry Pregnancy Risk Factors Collagen Metabolism Proteins Metabolism Hyperplasia Human Animal Studies Steroids Metabolism Flow Cytometry Lactation Female Inflammation Pathology Breast Neoplasms Pathology Risk Assessment Epithelial Cells Metabolism Biopsy Disease Susceptibility Gene Expression Profiling Validation Studies Comparative Studies Evaluation Research Multicenter Studies Short Portable Mental Status Questionnaire Female ab: Background: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood.Methods: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer.Results: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors.Conclusions: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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