TY - JOUR
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
Y1 - 2021/12
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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U2 - 10.1038/s41467-021-26505-3
DO - 10.1038/s41467-021-26505-3
M3 - Article
C2 - 34732713
AN - SCOPUS:85118580518
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6341
ER -