Biological staging of incipient, in situ and invasive breast carcinomas

The objective of breast cancer staging is to help define the natural history of tumor progression and clinical behavior. Experimental models showed different pathways for the development of breast tumors.’.’ In human breast cancer, the histological studies performed gave limited information about the molecular mechanisms of the cancerogenetic multistep process. The earliest morphologically recognizable lesions constitute a heterogeneous group with different progression potential; carcinoma in situ comprises, in fact, different entities: one (incipient tumors) with low and others with intermediate (ductal carcinoma in situ non-. comedo, lobular carcinoma in situ) or high (ductal carcinoma in situ comedo) risk of progression, respectively. At present, the most important problem is tounderstand the different biological meaning of precancerous proliferative lesions and invasive tumors. Several biological parameters, such as estrogen and progesterone receptors (ER, PK), proliferation index (PI), and oncogene and suppressor gene overexpression, are becoming increasingly important as prognostic adjuncts to standard morphological eval~ation.~-T*h is could be useful to characterize early lesions (carcinoma in situ) as well as invasive tumors detected by screening mammography (small size, special types, and node-negative). In recent years, the immunohistochemical (ICA) demonstration of biological markers has brought about considerable advantages, allowing their direct visualization in tissue and cytological pecimens. Moreover, the development of computerized image analysis systems has provided a quantitative evaluation of biological markers. In this study, 1895 primary invasive (collected since 1985) and 49 in situ (collected since 1991) carcinomas were biologically characterized and ICA assays were measured by an image analysis system (CAS 200 BD).”-I4 The relationships between biological and pathological parameters (node status, size, histotype) were studied with a multivariate analysis. A cluster analysis was performed with the aim to classify cases into subgroups, according to their biological profile. Clinical usefulness of biological assessment was evaluated in 461 patients (median follow-up of 71.6 months). This study underlines the importance of the biological profile, which may be used in concert with other factors to help identify tumor outcome.