ASPO Abstracts
Uncovering spatial relationships of the tumor microenvironment in the Carolina Breast Cancer Study
Category: Cancer Health Disparities
Conference Year: 2020
Abstract Body:
Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Although
breast cancer mortality rates have dropped over the last few decades, the mortality rate for Black women is still
40% higher than White women. Even among the breast cancer subtype with the best prognosis (ER+/HER2-),
Black women still have a higher risk of recurrence (ROR). Some work has been done to uncover differences in the
biology of breast cancer between White and Black women, but there has been little study of how immune
responses differ by race. To identify spatial relationships between tumor and specific immune subpopulations in
the microenvironment of breast cancer, we performed digital spatial profiling (DSP) of tumor whole sections and
tumor microarrays from the Carolina Breast Cancer Study (CBCS), a large population-based study that
oversampled for Black and younger women. DSP identifies relationships among immune subpopulations,
analyzing approximately 40 immune markers in areas selected for CD45, CD68, or pan-cytokeratin content. Thus
immune ‘hot spots’ and tumor microenvironment can be evaluated separately. In whole tumor slides, we found that
immune hot spots (with high CD45 infiltrations) had elevated expression of many immune markers, suggesting
that there was a widespread, robust immune response that included Macrophages, Dendritic cells, B-cells, and T-
cells. However, we also observed that immune markers were detectable in tumor-enriched areas, and that tumor-
enriched areas had distinct immune signals depending upon subtype, with Tregulatory cell markers being higher in
Basal-like and Dendritic cell markers being higher in Luminal A breast cancers. Extending these findings to tumor-
enriched material on TMAs, we evaluated 76 patients and once again found subtype-specific immune responses,
including enrichment of Tregulatory cell markers in Basal-like breast cancers. DSP elucidates spatial differences in
the tumor microenvironment and highlights how whole slide and TMA specimens can be used to understand the
breast cancer microenvironment by subtype. The contribution of race to these immune responses will require
larger numbers of tumors of specific subtypes, as there are strong immune response differences by subtype.
Keywords: Spatial Immune Microenvironment, Breast Cancer