Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers

Joshua Ogony, Tanya L. Hoskin, Melody Stallings-Mann, Stacey Winham, Rushin Brahmbhatt, Muhammad Asad Arshad, Nagarajan Kannan, Alvaro Peña, Teresa Allers, Alyssa Brown, Mark E. Sherman, Daniel W. Visscher, Keith L. Knutson, Derek C. Radisky, Amy C. Degnim

Research output: Contribution to journalArticlepeer-review


Purpose: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. Methods: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. Results: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. Conclusions: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Jan 2023


  • BRCA mutations
  • Benign breast disease
  • Breast lobule
  • Immune cells
  • Immune microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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