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

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

doi:10.1038/s41467-021-26505-3

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.

Highlights

Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity
To gain insight into the features that could lead to poorer outcomes in postpartum breast cancer (PPBC) patients, we focused our analyses on clinically determined estrogen receptor (ER)+ cases, as ≥65% of all young breast cancer patients (≤45 years of age) are diagnosed with ER+ disease[53]
Of 40 selected cases, 16 ER+ cases (PPBC n = 9, nulliparous breast cancers (NPBC) n = 7) yielded RNA in sufficient quantity and quality to advance to RNA sequencing and subsequent gene expression analyses

Summary

Introduction

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. 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. These results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes. An elevated proportion of poor prognostic hormone receptor (HR)-negative and HER2-positive breast cancers is often cited to account for the adverse outcomes in young patients[15,16,17,18]. In the same US SEER study reporting a

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Conclusion