Background: The dominant invasive breast cancer histologic subtype, ductal carcinoma, shows intrinsic subtype diversity. However, lobular breast cancers are predominantly Luminal A. Both histologic subtypes show distinct relationships with patient and tumor characteristics, but it is unclear if these associations remain after accounting for intrinsic subtype. Methods: Generalized linear models were used to estimate relative frequency differences (RFDs) and 95% confidence intervals (95% CIs) for the associations between age, race, tumor characteristics, immunohistochemistry (IHC) and RNA-based intrinsic subtype, TP53 status, and histologic subtype in the Carolina Breast Cancer Study (CBCS, n = 3,182) and The Cancer Genome Atlas (TCGA, n = 808). Results: Relative to ductal tumors, lobular tumors were significantly more likely to be Luminal A [CBCS RNA RFD: 44.9%, 95% CI (39.6, 50.1); TCGA: RFD: 50.5%, 95% CI (43.9, 57.1)], were less frequent among young (≤ 50 years) and black women, were larger in size, low grade, less frequently had TP53 pathway defects, and were diagnosed at later stages. These associations persisted among Luminal A tumors (n = 242). Conclusions: While histology is strongly associated with molecular characteristics, histologic associations with age, race, size, grade, and stage persisted after restricting to Luminal A subtype. Histology may continue to be clinically relevant among Luminal A breast cancers.
Bibliographical noteFunding Information:
We would like to thank that participants who generously participated in these studies. This work was supported by the Komen Graduate Training and Disparities Research Training Grant (LAW); Komen Career Catalyst Grant (CCR16376756) (KAH); National Institutes of Health: P50 CA058223 and U01 CA179715 (AFO and MAT); R01 HG009125, P01 CA142538, and P30 ES010126 (MIL), and U54 CA156733 (MAT), R01 CA19575401 (CMP).
- Breast cancer
- Histologic subtype
- Intrinsic subtype