Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles

Cells. 2022 Jul 24;11(15):2286. doi: 10.3390/cells11152286.


Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+/HER2- breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.

Keywords: PD-L1; biomarkers; breast cancer; breast cancer during pregnancy; early-onset breast cancer; pregnancy-related breast cancer; tumor microenvironment; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating
  • Neoplasm Recurrence, Local / pathology
  • Pregnancy
  • Pregnancy Complications, Neoplastic* / immunology
  • Pregnancy Complications, Neoplastic* / pathology
  • Tumor Microenvironment*


  • B7-H1 Antigen

Grant support

This research was partially funded by the Oncomine Clinical Research Grant Program.