In a Danish nationwide prospective study of in situ carcinoma of the breast, a total of 275 women, treated with excision alone, were registered from 1982 to 1989. The series included 142 cases of ductal carcinoma in situ (DCIS), 100 cases of lobular carcinoma in situ (LCIS), 26 cases of DCIS+LCIS, and seven cases of atypical hyperplasia (AH). Within a median follow-up of 120 months, a crude recurrence rate of 28% (76 cases) was found, of which 53% (40 cases) recurred as invasive carcinomas (IC) and 47% (36 cases) as CIS. CIS recurrences appeared after median 18 months, compared to median 42 months for IC recurrences. No statistical difference was found with respect to development of IC between the three groups of DCIS, DCIS+LCIS, and LCIS. The majority of recurrences were ipsilateral, also for LCIS. Forty four of 49 recurrences following DCIS, and seven of nine recurrences following DCIS+LCIS occurred as local recurrences. Histopathologically, in DCIS a strong association was found between large nuclear size and comedonecrosis. Univariate analysis showed a significant association to recurrence for nuclear size, comedonecrosis, and size of the original lesion. Multivariate analysis showed that only comedonecrosis and size of lesion were independent predictors of recurrence, however, specimen margins were not included in the analysis, as this parameter could not be adequately evaluated in the present series. Nuclear size of original DCIS lesion was related to histologic grade of the IC recurrence. The recurrence rate for DCIS of small nuclear size increased from 6% at five years of follow-up to 16% at 10 years, possibly due to a slower growth rate and a continued but delayed risk. Similarities were found between LCIS and DCIS of small nuclear size, both showing a continued risk and comparable rate of recurrence. Further, progression to IC of similar, highly differentiated type was seen, indicating a linkage between biological behavior of the two histological types.

The coding region determinant binding protein (CRD-BP) was isolated by virtue of its high affinity to the c-myc mRNA coding region stability determinant and shown to shield this message from nucleolytic attack, prolonging its half -life. CRD-BP is normally expressed during fetal life but is also activated de novo in tumors. Considering that aberrant CRD-BP expression may represent an additional mechanism interfering with c-myc regulation, we screened 118 primary breast carcinomas for CRD-BP expression, 60 of which had also been analyzed by comparative genomic hybridization (CGH). Copy number gains encompassing 8q24, the chromosome band that contains the c-myc locus, were detected in 48.3% (29/60) of tumors, whereas gains involving band 17q21, which contains the CRD-BP locus, were observed in 18.3% (11/60) of tumors. CRD-BP expression was detected in 58.5% (69/118) of tumors, implying mechanisms of activation alternative to gene amplification. Altogether, some 75% of the tumors had alterations pertaining to c-myc since they either harbored 8q24 gains and/or expressed CRD-BP. Significant associations were detected between CRD-BP expression and the absence of estrogen receptors (p ‫؍‬ 0.005) and between the presence of 8q24 gains and an increased number of genomic changes as measured by CGH (p ‫؍‬ 0.0017). Tumors were divided into 4 groups according to CRD-BP expression and 8q24 gains. The odds for tumors having both characteristics to be classified as poorly differentiated (grade III vs. grade I and II) were 19.6 times the corresponding odds for tumors neither expressing CRD-BP nor harboring 8q24 gains. For tumors either harboring 8q24 gains only or expressing CRD-BP alone, the corresponding odds were 6.4 and 3, respectively.

We have investigated the localization of urokinase-type plasminogen activator (u-PA), type-I plasminogen-activator inhibitor (PAL I), U-PA receptor (u-PAR) and q-macroglobulinreceptor/low-density-lipoprotein-receptor-related protein (a2MR/LRP) in human breast tumors by immunohistochemical methods. Frozen sections of I33 primary breast carcinomas, 6 ductal carcinomas in situ and 33 lymph-node metastases were stained with monoclonal antibodies. Formalin-fixed sections of I 5 primary tumors and 2 lymph-node metastases were stained with polyclonal antibodies. In primary tumors, u-PA and PAI-I immunoreactivities were intense in macrophages and mast cells, and moderate in benign and malignant epithelial cells as well as in myofibroblasts and endothelial cells. A sub-group of poorly differentiated tumors showed particularly strong staining of stromal fibroblasts. U-PA immunoreactivity was also present in lymphocytes. a,MR/LRP and U-PAR immunoreactivities were intense in macrophages, but apart from these cells, a,MR/LRP was found only in fibroblasts, and U-PAR only in tumor cells located peripherally in tumor-cell clusters and glands and some myofibroblasts in the adjacent stroma. Lymphnode metastases showed staining for u-PA and PAI-I both of cancer cells and of stromal fibroblasts, also staining for U-PA of lymphocytes. Similarly to some of the poorly differentiated primary tumors, approximately half of the metastases showed very strong staining of stromal fibroblasts, and extracts of these metastases had higher U-PA and PAI-I levels, as determined by ELISA, than extracts of metastases without this staining pattern. qMR/LRP was present only in fibroblasts and U-PAR only in some tumor cells. The presence of u-PA, PAI-I, alMR/LRP and U-PAR was controlled biochemically by immunoblotting analyses, ligand-blotting analyses, and direct and reverse zymography. The spatial distribution and the variation in concentration of the various components of the plasminogen-activation system point to a complex, multifunctional role for the 4 proteins in and/or during the development and spread of breast cancer.o 1996 Wiley-Liss, Inc.

A review of 3299 benign breast lesions was carried out. Lobular carcinoma in situ (LCIs) was discovered in 52 cases; and of these, 44 had been treated by biopsy alone. During the follow-up period averaging 15.9 years, 11 patients developed invasive breast cancer (IBC): 9 ipsilateral lesions, and 4 contralateral. This was about 12 times the frequency expected. The development of IBC had no relation to the patient's age, nor could any correlation be drawn between the time periods which elapsed from the time of the diagnosis of the in situ cancer to the development of IBC. The ipsilateral occurrence of IBC was not isgnificantly different from the contralateral. Careful lifelong follow-up seems to be the rational treatment for women whose breast biopsy shows LCIs.

In a study of breasts from 83 consecutive, unselected female autopsies, 23 women (28%) were found to have radial scars. The lesion was multicentric in 67% and bilateral in 43%. The frequency of radial scar was significantly increased among women with fibrocystic disease (43%) compared to women without this lesion (17%). No difference in the frequency of radial scar was registered between women with primary breast malignancy and women with either normal breasts or benign breast abnormalities. No radial scar demonstrated transition to invasive or in situ carcinoma. No evidence was found of any association between radial scar and breast carcinoma.