Prognostic variables in invasive breast cancer: Contribution of comedo versus noncomedo in situ component

Background: Many invasive breast cancers are accompanied by a variety of noninvasive components. Histological distinctions have been made between these components, but to understand their importance, it is essential to examine their molecular biology. Methods: Proliferative indices, oncoproteins, and steroid receptor expression were compared for invasive breast cancers containing comedo-type ductal carcinoma in situ (n=35), noncomedo-type ductal carcinoma in situ (n=34), and pure invasive cancers (n=49). Ploidy, S-phase fraction, Ki-67 staining, estrogen receptor (ER), progesterone receptor (PR), and the expression of HER-2/neu and epidermal growth factor receptor (EGFR) were evaluated in these tumors. Results: The comedo-invasive subgroup differed significantly from the noncomedoinvasive subgroup, demonstrating significantly higher mean ploidy (1.6 vs. 1.3;p=0.0156), S-phase fraction (7.9% vs. 4.3%;p=0.0066), Ki-67 staining (20.3% vs. 12.0%;p=0.0058), and HER-2/neu values (2,247 fm/mg vs. 1,014 fm/mg;p=0.0412) and lower ER (76 fm/mg vs. 339 fm/mg;p=0.006) and PR values (99 fm/mg vs. 265 fm/mg;p=0.0608). A higher percentage of comedo-invasive carcinomas demonstrated aneuploidy (71%;p=0.0158), elevated levels of S-phase fraction (75%;p=0.0016) and Ki-67 staining (55%;p=0.0512), overexpression of HER-2/neu oncogene (47%;p=0.0011), and were ER negative (35%;p=0.0148), PR negative (47%;p=0.0073) when compared to noncomedo-invasive carcinomas. Comedo-invasive and noncomedo-invasive tumors were comparable for nodal status and tumor size, but differences were noted for tumor differentiation and percentage of tumors that were >1 cm. Comedo-invasive tumors were predominantly poorly differentiated (60 vs. 32%) and were >1 cm (94 vs. 77%, p<0.05). Results: Comedo-invasive cancers were comparable to pure invasive cancers for ploidy, S-phase fraction, Ki-67 staining, and ER, PR, and EGFR expression. However, comedoinvasive carcinomas had greater HER-2/neu overexpression when compared to pure invasive tumors (47 vs. 19%;p=0.0359). Conclusions: These results are consistent with the hypothesis that comedo carcinoma is a more aggressive type of ductal carcinoma in situ and may have independent prognostic value when seen in association with infiltrating ductal carcinoma. In invasive tumors, comedo carcinomas are associated with poor prognostic factors, including higher ploidy, S-phase fractions, Ki-67 staining, negative ER and PR status, poorer differentiation, larger tumors, and presence of HER-2/neu oncogene overexpression.