The Landscape of Immune Microenvironments in Racially Diverse Breast Cancer Patients
Year: 2022
Type: article
Abstract: BACKGROUND: Immunotherapy is a rapidly evolving treatment option in breast cancer; However, the breast cancer immune microenvironment is understudied in Black and younger (<50 years) patients. METHODS: We used histologic and RNA-based immunoprofiling methods to characterize the breast cancer immune landscape in 1,952 tumors from the Carolina Breast Cancer Study (CBCS), a population-based study that oversampled Black (n = 1,030) and young women (n = 1,039). We evaluated immune response leveraging markers for 10 immune cell populations, compared profiles to those in The Cancer Genome Atlas (TCGA) Project [n = 1,095 tumors, Black (n = 183), and young women (n = 295)], and evaluated in association with clinical and demographic variables, including recurrence. RESULTS: Consensus clustering identified three immune clusters in CBCS (adaptive-enriched, innate-enriched, or immune-quiet) that varied in frequency by race, age, tumor grade and subtype; however, only two clusters were identified in TCGA, which were predominantly comprised of adaptive-enriched and innate-enriched tumors. In CBCS, the strongest adaptive immune response was observed for basal-like, HER2-positive (HER2+), triple-negative breast cancer (TNBC), and high-grade tumors. Younger patients had higher proportions of adaptive-enriched tumors, particularly among estrogen receptor (ER)-negative (ER-) cases. Black patients had higher frequencies of both adaptive-enriched and innate-enriched tumors. Immune clusters were associated with recurrence among ER- tumors, with adaptive-enriched showing the best and innate-enriched showing the poorest 5-year recurrence-free survival. CONCLUSIONS: These data suggest that immune microenvironments are intricately related to race, age, tumor subtype, and grade. IMPACT: Given higher mortality among Black and young women, more defined immune classification using cell-type-specific panels could help explain higher recurrence and ultimately lead to targetable interventions.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Susan G. Komen for the Cure, Tessa Therapeutics, National Institutes of Health, Gillings School of Public Health, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Environmental Health Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Awards: G1434892013, G2627953802, G4574274672, G534517478, G7047688319, Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium, Impact of the Breast Cancer Immune Microenvironment on Racial Disparities and Survivorship, P53, DNA Repair Imbalance, and Immune Response in Breast Cancer Mortality Disparities, UNC Center for Environmental Health and Susceptibility, SPORE in Breast Cancer, The role of B-cells in the anti-tumor immune response in triple negative breast cancer, Cancer Center Support Grant, Cancer Control Education Program, G958207224
OpenAlex ID: W4224217428