Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Sonali Jindal; Nathan D. Pennock; Duanchen Sun; Wesley Horton; Michelle K. Ozaki; Jayasri Narasimhan; Alexandra Q. Bartlett; Sheila Weinmann; Paul E. Goss; Virginia F. Borges; Zheng Xia; Pepper Schedin

doi:10.1038/s41467-021-26505-3

Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Sonali Jindal, Nathan D. Pennock, Duanchen Sun, Wesley Horton, Michelle K. Ozaki, Jayasri Narasimhan, Alexandra Q. Bartlett, Sheila Weinmann, Paul E. Goss, Virginia F. Borges, Zheng Xia, Pepper Schedin

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

Original language	English (US)
Article number	6341
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26505-3
State	Published - Dec 1 2021

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{1d0cac145e0140f0abac627383915b93,

title = "Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes",

abstract = "Young women{\textquoteright}s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.",

author = "Sonali Jindal and Pennock, {Nathan D.} and Duanchen Sun and Wesley Horton and Ozaki, {Michelle K.} and Jayasri Narasimhan and Bartlett, {Alexandra Q.} and Sheila Weinmann and Goss, {Paul E.} and Borges, {Virginia F.} and Zheng Xia and Pepper Schedin",

note = "Funding Information: This work was funded by grant NIH/NCI R01#1CA169175 to P.S. and V.F.B.; the Willard L. and Ruth P. Eccles Foundation, the Coit Family Foundation, Oregon Health & Science University—School of Medicine Faculty Innovation Funds, and Oregon Clinical and Translational Research Institute (OCTRI)–Kaiser Permanente Northwest tissue retrieval funds, and the Knight Cancer Institute to P.S.; and funding from the Avon Foundation to P.G. We also want to thank Colorado{\textquoteright}s NIH/NCI Cancer Center Support Grant P30CA046934, the Knight Cancer Institute{\textquoteright}s Cancer Center Support Grant P30CA69533, NIH-OD011092 for the Oregon National Primate Research Center Bioinformatics and Biostatistics Core, and NIH/NLM K01 K01LM012877 (to Z.X.) and the Collins Medical Trust grant (to Z.X.). The funding bodies listed above played no role in; the design of the study, collection, analysis, or interpretation of data, nor were they involved in the preparation of this manuscript. The authors wish to acknowledge the Gene Profiling Shared Resource and Massive Parallel Sequencing Shared resources at OHSU for oversight for isolation and sequencing of RNA, Kristin Muessig and Chalinya L Ingphakorn (Kaiser Permanente Northwest) for administrative support; Weston Anderson for excellent support in review and editing of the manuscript and Wendy Ingman and Sarah Bernhardt for assistance in computing pseudo-Oncotype Dx{\textregistered} scores. RNA extractions were performed by the OHSU Gene Profiling Shared Resource. Illumina sequencing was performed by the OHSU Massively Parallel Sequencing Shared Resource. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

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doi = "10.1038/s41467-021-26505-3",

language = "English (US)",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

AU - Jindal, Sonali

AU - Pennock, Nathan D.

AU - Sun, Duanchen

AU - Horton, Wesley

AU - Ozaki, Michelle K.

AU - Narasimhan, Jayasri

AU - Bartlett, Alexandra Q.

AU - Weinmann, Sheila

AU - Goss, Paul E.

AU - Borges, Virginia F.

AU - Xia, Zheng

AU - Schedin, Pepper

N1 - Funding Information: This work was funded by grant NIH/NCI R01#1CA169175 to P.S. and V.F.B.; the Willard L. and Ruth P. Eccles Foundation, the Coit Family Foundation, Oregon Health & Science University—School of Medicine Faculty Innovation Funds, and Oregon Clinical and Translational Research Institute (OCTRI)–Kaiser Permanente Northwest tissue retrieval funds, and the Knight Cancer Institute to P.S.; and funding from the Avon Foundation to P.G. We also want to thank Colorado’s NIH/NCI Cancer Center Support Grant P30CA046934, the Knight Cancer Institute’s Cancer Center Support Grant P30CA69533, NIH-OD011092 for the Oregon National Primate Research Center Bioinformatics and Biostatistics Core, and NIH/NLM K01 K01LM012877 (to Z.X.) and the Collins Medical Trust grant (to Z.X.). The funding bodies listed above played no role in; the design of the study, collection, analysis, or interpretation of data, nor were they involved in the preparation of this manuscript. The authors wish to acknowledge the Gene Profiling Shared Resource and Massive Parallel Sequencing Shared resources at OHSU for oversight for isolation and sequencing of RNA, Kristin Muessig and Chalinya L Ingphakorn (Kaiser Permanente Northwest) for administrative support; Weston Anderson for excellent support in review and editing of the manuscript and Wendy Ingman and Sarah Bernhardt for assistance in computing pseudo-Oncotype Dx® scores. RNA extractions were performed by the OHSU Gene Profiling Shared Resource. Illumina sequencing was performed by the OHSU Massively Parallel Sequencing Shared Resource. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

AB - Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

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Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

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