The clinical behavior of breast carcinoma is Probably determined at the preinvasive stage (Ductal carcinoma in Situ)

BACKGROUND: Mammography has greatly increased the number of women diagnosed with ductal carcinoma in situ (DCIS) of the breast. New classifications of DCIS recently have been proposed. In this study, these classifications were applied to DCIS associated with invasive tumors and correlated with patient prognosis. METHODS: Three hundred cases of infiltrating ductal carcinoma of the breast in which there was associated DCIS in the surrounding breast were studied. The DCIS was classified as well, moderately, or poorly differentiated, according to two recently published systems using the cytonuclear features of the malignant cells (Holland classification) and cytology and the presence of necrosis (Van Nuys classification). RESULTS: The differentiation of DCIS was significantly correlated with the grade of the invasive carcinoma (P < 0.0001), the Nottingham prognostic index (P < 0.0001), and the clinical outcomes of the patients (P < 0.0001). CONCLUSIONS: These findings indicate that a model in which there is increasing in situ dysplasia before the development of stromal invasion is incorrect for breast carcinoma. Rather, in most cases, well-differentiated DCIS probably gives rise to low grade invasive breast carcinoma with a better long term clinical outcome. These data suggest that many of the important prognostic biologic and genetic characteristics of breast carcinoma are already established in the neoplastic clones of malignant cells at the preinvasive stage of the disease.