Ductal Carcinoma in Situ of the Breast: a New Phenotype Classification System and its Relation to Prognosis

Center for Police Research, Uppsala University, Uppsala, Uppsala, Sweden
Breast Cancer Research and Treatment (Impact Factor: 3.94). 07/2002; 73(3):215-21. DOI: 10.1023/A:1015816406078
Source: PubMed


In a study of invasive breast cancer, multiple correspondence analysis (MCA) revealed clustering of eight pathobiological variables. Two different phenotypes were distinguished by an index calculated on the basis of the variables (histologic grade, necrosis, lymphoid infiltration, number of mitosis and expression of c-erbB-2, p53, progesterone receptor and Bcl-2). Phenotype A lesions share most of the features of normal breast tissue. Phenotype B looks more malignant, has a higher early recurrence rate and is more frequently seen in younger patients. Our aim was to see if ductal breast carcinoma in situ (DCIS) could be divided into the same phenotypes. One hundred and eighty DCIS were investigated. Association between the eight variables was studied in 2 x 2 models. The phenotype index was calculated by summing weights for the variables in the MCA. All variables were associated, except Bcl-2. DCIS was divided in two phenotypes. Thirty-three tumours were Phenotype A and 147 Phenotype B. The mean age at diagnosis was 65.5 and 58.4 years for Phenotypes A and B, respectively (p = 0.0012). No difference regarding local relapse free survival was seen. Two phenotypes were distinguished in DCIS, similar to invasive breast cancer. In an earlier study, 45% of the invasive cancers were classified as Phenotype B. In this study, 82% of DCIS were Phenotype B. This may indicate that invasive breast cancer of Phenotype B is derived from DCIS of Phenotype B. The distribution of DCIS phenotypes with a small proportion of Phenotype A DCIS may be due to that Phenotype A DCIS is less likely to be detected by mammography, or that some invasive breast cancers of Phenotype A progress to invasiveness without passing the in situ phase.

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    ABSTRACT: Geno-phenotypic patterns of pre-invasive and invasive lobular breast cancers and infiltrating ductal carcinomas of low, intermediate, and high grade are reviewed. One of the main differences between lobular breast cancers and ductal carcinomas is the presence of inactivating E-cadherin gene mutations in lobular breast cancers. In many other respects, lobular breast cancers and low-grade ductal carcinomas exhibit similar geno-phenotypic profiles. The development of p53 dysfunction may be a hallmark of infiltrating ductal cancers of intermediate and high grade. Sequential Her-2/neu and ras abnormalities define a subset of aggressive high-grade tumors, and the development of Rb dysfunction may define a separate subset of aggressive ductal cancers. Based on these observations, a branching molecular evolutionary model for the development and progression of breast cancer is proposed.
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    ABSTRACT: The incidence of ductal carcinoma in situ (DCIS), a noninvasive form of breast cancer, has increased markedly in recent decades, and DCIS now accounts for approximately 20% of breast cancers diagnosed by mammography. Laboratory and patient data suggest that DCIS is a precursor lesion for invasive cancer. The appropriate classification of DCIS has provoked much debate; a number of classification systems have been developed, but there is a lack of uniformity in the diagnosis and prognostication of this disease. Further investigation of molecular markers should improve the classification of DCIS and our understanding of its relationship to invasive disease. Controversy also exists with regard to the optimal management of DCIS patients. In the past, mastectomy was the primary treatment for patients with DCIS, but as with invasive cancer, breast-conserving surgery has become the standard approach. Three randomized trials have reported a statistically significant decrease in the risk of recurrence with radiation therapy in combination with lumpectomy compared with lumpectomy alone, but there was no survival advantage with the addition of radiotherapy. Two randomized trials have suggested an additional benefit, in terms of recurrence, with the addition of adjuvant tamoxifen therapy, although in one trial the benefit was not statistically significant. Current data suggest that tamoxifen use should be restricted to patients with estrogen receptor-positive DCIS. Neither trial demonstrated a survival benefit with adjuvant tamoxifen. Ongoing and recently completed studies should provide information on outcomes in patients treated with lumpectomy alone and on the effectiveness of aromatase inhibitors as an alternative to tamoxifen.
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    ABSTRACT: OBJECTIVES: The aim of the present study was to evaluate the nuclear grade, the expressions of p53 and c-erbB-2 proteins, and the estrogen receptors (ER) of 38 women with ductal carcinoma in situ (DCIS) and invasive carcinoma of the same breast. METHODS: the protein profile of 38 women was investigated in a descriptive and retrospective study, through the immune-histochemical technique. The cut-off limit for positive staining was chosen at 10% or more of positive cells for p53 and c-erbB-2 proteins and for ER. The analysis of the concordance between the expressions of proteins and the nuclear grade was done by the kappa coefficient, according to Landis and Koch's criteria. MacNemar's test was used to assess the differences between the two groups. RESULTS: there was a perfect concordance in the expression of p53 proteins (kappa coefficient = 1.00) and almost a perfect concordance for c-erbB-2 proteins, ER and nuclear grade (kappa coefficients = 0.84, 0.89 and 0.89) between in situ and invasive elements of the same tumor. CONCLUSION: there was no difference between the expressions of p53 and c-erbB-2 proteins, ER and nuclear grade in the DCIS and invasive carcinoma of the same breast.
    Preview · Article · Jul 2004 · Revista Brasileira de Ginecologia e Obstetrícia
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