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Title:
Postpartum breast involution reveals regression of secretory lobules mediated by tissue-remodeling | Breast Cancer Research
Description:
Introduction A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women. Methods Adjacent normal breast tissues from premenopausal women (nâ=â183) aged 20 to 45 years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods. Results Human nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12 months postpartum. By 18 months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame. Conclusions Human postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.
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Keywords {đ}
breast, postpartum, cancer, type, lobules, lobular, pubmed, lobule, cases, involution, article, nulliparous, google, scholar, figure, years, composition, women, gland, tissue, mammary, cell, pregnancy, analysis, area, months, cas, types, number, lactation, cohort, data, human, study, parous, age, acini, schedin, observed, immune, reproductive, compared, file, tumor, cells, size, additional, central, error, research,
Topics {âď¸}
steroidal anti-inflammatory drugs article download pdf pro-tumorigenic extracellular matrix weaning-induced breast involution dominant tissue-remodeling process post-partum breast cancer benign-disease breast tissues tumor cell migration mouse mammary gland node-negative breast cancer nsaid-based intervention targeted epithelial cell death weeks post-weaning corroborate age-related lobular involution mammary gland involution mammary epithelial cells identify age-related involution mammary gland morphological postpartum mammary gland epithelial cell proliferation confound lobule-type quantitation dominant regression program apoptotic cell death mammary tissue remodeling mammary epithelial area privacy choices/manage cookies programmed cell death postpartum gland involution provenzano pp grant numbers bc104000 full size image early involution event apoptotic epithelial cells confirmed previous reports article number r31 colorado cancer center watson cj breast cancer outcomes mammary gland development postpartum breast involution o'neill ma borges & pepper schedin normal breast tissues exp cell res registry-based cohort study o'brien collagen remodeling characterize fibrillar collagen deposition retrospective chart review obtained grant funding
Questions {â}
- Borges VF, Schedin P: Could NSAIDS become preventative therapy in pregnancy-associated breast cancer?
- O'Brien J, Schedin P: Macrophages in breast cancer: do involution macrophages account for the poor prognosis of pregnancy-associated breast cancer?
- Vierkant RA, Hartmann LC, Pankratz VS, Anderson SS, Radisky D, Frost MH, Vachon CM, Ghosh K, Distad TJ, Degnim AC, Reynolds CA: Lobular involution: localized phenomenon or field effect?
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headline:Postpartum breast involution reveals regression of secretory lobules mediated by tissue-remodeling
description:A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women. Adjacent normal breast tissues from premenopausal women (nâ=â183) aged 20 to 45Â years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods. Human nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12Â months postpartum. By 18Â months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame. Human postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.
datePublished:2014-03-28T00:00:00Z
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headline:Postpartum breast involution reveals regression of secretory lobules mediated by tissue-remodeling
description:A postpartum diagnosis of breast cancer is an independent predictor of metastases, however the reason is unknown. In rodents, the window of postpartum mammary gland involution promotes tumor progression, suggesting a role for breast involution in the poor prognosis of human postpartum breast cancers. Rodent mammary gland involution is characterized by the programmed elimination of the secretory lobules laid down in preparation for lactation. This tissue involution process involves massive epithelial cell death, stromal remodeling, and immune cell infiltration with similarities to microenvironments present during wound healing and tumor progression. Here, we characterize breast tissue from premenopausal women with known reproductive histories to determine the extent, duration and cellular mechanisms of postpartum lobular involution in women. Adjacent normal breast tissues from premenopausal women (nâ=â183) aged 20 to 45Â years, grouped by reproductive categories of nulliparous, pregnant and lactating, and by time since last delivery were evaluated histologically and by special stain for lobular area, lobular type composition, apoptosis and immune cell infiltration using computer assisted quantitative methods. Human nulliparous glands were composed dominantly of small (approximately 10 acini per lobule) and medium (approximately 35 acini per lobule) sized lobules. With pregnancy and lactation, a >10 fold increase in breast epithelial area was observed compared to nulliparous cases, and lactating glands were dominated by mature lobules (>100 acini per lobule) with secretory morphology. Significant losses in mammary epithelial area and mature lobule phenotypes were observed within 12Â months postpartum. By 18Â months postpartum, lobular area content and lobule composition were indistinguishable from nulliparous cases, data consistent with postpartum involution facilitating regression of the secretory lobules developed in preparation for lactation. Analyses of apoptosis and immune cell infiltrate confirmed that human postpartum breast involution is characterized by wound healing-like tissue remodeling programs that occur within a narrowed time frame. Human postpartum breast involution is a dominant tissue-remodeling process that returns the total lobular area of the gland to a level essentially indistinguishable from the nulliparous gland. Further research is warranted to determine whether the normal physiologic process of postpartum involution contributes to the poor prognosis of postpartum breast cancer.
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Lobule Type
Lobular Involution
Reproductive Category
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Cancer Research
Oncology
Surgical Oncology
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