Early and more advanced unifocal and multifocal breast carcinomas and their molecular phenotypes

I examined the relationship between the recently established prognostic parameter, molecular tumor phenotype and tumor size, lesion distribution (unifocal, multifocal, diffuse growth), and lymph node status.

I analyzed 660 consecutive invasive breast carcinomas documented in large-format histology sections. Immunohistochemistry was used to phenotype the tumors on the basis of estrogen and progesterone receptor expression, HER2 (human epithelial growth factor receptor 2) overexpression, and expression of basal markers.

The proportion of luminal A tumors (84.8% vs. 71.6%; P < .0001) and basal-like tumors (5.0% vs. 14.8%; P < .0001) were significantly different in early (<15 mm) and more advanced invasive breast carcinomas, whereas the proportion of luminal B and HER2 type tumors (4.2% vs. 7.8%, and 5.7% vs. 4.8%, respectively) were not. All the phenotypes had similar percentages of multifocal tumors, whereas most diffuse invasive carcinomas were luminal A type. Early luminal A carcinomas had significantly fewer lymph node metastases (LNM) than more advanced carcinomas but luminal B and HER2 type tumors showed no such difference. This difference was evident (15.4% vs. 42.4%) but statistically not significant in the basal-like category. Multifocal tumors of all phenotypes had significantly higher frequencies of LNM compared with unifocal tumors.

Multifocality of the invasive component represents a negative prognostic parameter associated with significantly increased LNM in all phenotype, whereas larger tumor size was such a parameter only in the luminal A category. HER2 overexpression occurs early in the natural history of tumors and is associated with high LNM rates.