Management of ductal carcinoma in situ of the breast

The natural course of primary osteoarthritis of the knee with or without treatment by intraarticular corticosteroid injections was investigated in 446 patients presenting from 1970 to 1973. Sixty-one of these patients were able to be followed up in 1982 and were divided into two groups. One group included 53 patients (82 knees) without corticosteroid injections. The other group had eight patients (14 knees) who received intraarticular steroids (mean number of injections: 25; range:4-78). The standing femorotibial angle at followup in the male patients receiving injections (p < 0.05) was four degrees of greater varus angulation. Radiographic degeneration was more advanced in 11 of the 24 steroid-treated knees (78.6%), and in 43 of the 82 knees without steroid injections (52.4%) (p < 0.01).     

Cancerization of lobules and atypical ductal hyperplasia adjacent to ductal carcinoma in situ of the breast

The splitting of the functions of purchaser and provider in the New Zealand health system in 1993 necessitated the use of explicit contracts between the two parties. This paper examines contracting experiences during the first two years of operation. The study focuses on four services: rest homes, primary care clinics, surgical services, and acute mental health services. The insights of transaction cost economics form the theoretical framework. The objective of this study was to examine whether the transaction costs associated with contracting vary across the four different services, and whether different types of contracts and contractual relationships are emerging as transactors attempt to reduce these costs. Information was collected in a series of 53 interviews with purchasers and providers, together with any relevant documentation. The results suggest that the costs of contracting are indeed greater for some services than for others. Other variables such as the style of negotiations, the type and specificity of contracts and the degree of monitoring also differ across the four services. At this early stage of the reform process, there was little evidence that purchasers and providers were attempting to reduce transaction costs by negotiating more flexible, longer-term, relational contracts. The main benefit from contracting to date has been improved accountability of service providers.     

Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast

Multiple tumor suppressor genes are implicated in the oncogenesis and progression of invasive carcinoma of the breast. To investigate the chronology of genetic changes we studied loss of heterozygosity on chromosome 17 in ductal carcinoma in situ, a preinvasive breast cancer. A microdissection technique was used to separate tumor from normal stromal cells prior to DNA extraction and loss of heterozygosity was assayed mainly using simple sequence repeat polymorphism markers and the polymerase chain reaction. Loss of heterozygosity on 17p was observed in 8 of 28 tumors (29%) when compared with normal control DNA, whereas no loss was seen on 17q, suggesting that at least one locus on 17p is involved early in the development of breast cancer.     

Protein expression profiles in human breast ductal carcinoma and histologically normal tissue

Reference two-dimensional (2-D) gels are presented for human breast ductal carcinoma and histologically normal tissue. Whole biopsy fragments were analyzed, including epithelial and nonepithelial components. Thirty-five spots have been assigned by gel matching to the human liver SWISS-2DPAGE reference map and/or to the human primary keratinocyte IPG map from the Danish Center for Human Genome. N-terminal microsequencing was applied to confirm randomly chosen matching assignments and to identify six new spots. Protein expression profiles in ductal carcinoma and in normal breast tissue appeared to be similar, except for a pattern consisting of 32 spots, which were highly expressed in all carcinoma specimens, and less intense and occasionally undetectable in normal tissue. This difference was statistically significant. Assignment has been obtained for several spots, namely GRP94, GRP78, GRP75, mitochondrial HSP60, calreticulin, protein disulfide isomerase, peptidyl-prolyl cis-trans isomerase, collagen-binding protein 2, fructose bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, thioredoxin, cytochrome c oxidase VA subunit, tubulin beta isoform and macrophage migration inhibitory factor (MIF). The cancer- and tissue-specificity of the described pattern was assessed by matching to the Swiss-2DPAGE human liver, hepatoma, lymphoma, erythroleukemia reference maps. The pattern of 32 spots was found to be indicative of epithelial neoplasia.     

The intermediate filaments and prognostically oriented morphological classification in ductal breast carcinoma

The expression of cytokeratins 7, 8, 14, 18, 19 and vimentin was examined in 100 cases of ductal invasive breast carcinomas. While the predominantly diffuse immunohistological positivity of simple epithelia cytokeratins 7 (in 93), 8 (in 100), 18 (in 100) and 19 (in 97) cases represents a constant feature of these tumors, cytokeratin 14 was detected in only 36 cases which were mostly of low grade and in a focal pattern. Vimentin positivity was found in 53 intermediate and high grade tumors and, again the pattern was also rarely diffuse. The ductal carcinomas can be grouped into four classes according to vimentin and cytokeratin 14 immunoreactivity. This grouping correlates well with tumor grade and with simple histological classification of ductal breast carcinoma, consisting of the low, intermediate and high malignancy categories, as proposed here. The types ofductal carcinomas can be sorted into prognostically different subgroups, according to ICD-O morphologic terminology and commonly adopted results of morphologic and prognostic studies.     

Tenascin expression in elastotic cuffs of invasive ductal carcinoma of the breast

We studied immunohistochemically one thousand one hundred and thirty-seven cases of primary invasive breast cancers (NST) and adjacent normal mammary glands for tenascin expression, and compared their elastic content to verify if a relationship exists between tenascin expression and elastosis. Periductal, perivascular and stromal elastosis were graded on a scale from 0 to 3 (absent to massive). All carcinomas showed tenascin expression and elastosis with various histological appearances. In the adjacent breast, teanscon was distributed around the normal ducts or with extasia and uctal hyperplasia without atypia. Digestion of the sections with elastase prior to staining resulted in a loss of the specific staining reactions in all areas where elastosis was present. Tenascin staining was observed in the mesenchyme closely surrounding the neoplastic ducts and the cancer cell nests. Stromal tenascin staining appeared stronger in those carcinomas that exhibited marked desmoplastic reactions. The highly differentiated tumours contained more elastosis in their tumour tissue than the poorly differentiated ones, whereas tenascin expression was stronger in poorly differentiated tumours than well differentiated tumours. A strong staining for tenascin was observed in the elastotic cuff. Tenascin staining did not disappear afterwards with elastase. We did not find a statistically significant correlation between tenascin expression, elastosis and prognostic factors such as size of the tumour, lymph node metastasis, tumour necrosis and age. In our study tenascin proved to be an additional element in elastotic areas even though the significance of an association between elastosis and tenascin is still unknown, as is that of elastosis itself.     

Tc-99m sestamibi uptake in infiltrating ductal carcinoma of the breast in a male patient

A 73-year-old man had an asymptomatic, slowly growing breast nodule. The mammographic appearance was highly suspicious of a malignancy, but the patient refused to undergo a biopsy. Because breast carcinoma has been previously described to accumulate Tc-99m MIBI in women, mammoscintigraphy was performed as a complementary examination. Uptake of the agent was noted.     

Cellular proliferation in breast ductal infiltrating carcinoma. Correlation with clinical and histopathological variables

To evaluate four methods to study cellular proliferation (mitotic count, mitotic index, PCNA and MIB1) in a series of breast ductal invasive cancer NOS, and the possible correlations between these different methods and other pathological variables, we studied 110 ductal invasive carcinomas NOS specimens. Mitoses per 1000 tumor cells and per 10 HPF, and immunostaining for PCNA and MIB1 were evaluated. Other accepted prognostic factors such as tumor size, histologic grade, estrogen and progesterone receptors measured by immunostaining and axillary status were obtained. Correlation between the four methods to evaluate cellular proliferation and these other variables was performed. Mitotic count, mitotic index, PCNA and MIB1 showed a good rate of correlation (r = 0.71-0.53, p < 0.05), with the exception of MIB1-mitotic index which was weak (r = 0.38, p < 0.05). A strong association between cellular proliferation, with independence of the method applied, and histologic grade, ER and PR was obtained. No association was observed with tumor size and lymph node involvement. In conclusion, there was a strong correlation between the four methods to evaluate cellular proliferation. Mitotic count (per 10 HPF) and MIB1 show a better correlation with other morphological variables. None of the evaluated methods are associated with the tumor size and axillary status, suggesting that mitotic count is the most accurate method to analyse cellular proliferation in routine practice.     

Evidence of significant apoptosis in poorly differentiated ductal carcinoma in situ of the breast

Following breast-conserving surgery for ductal carcinoma in situ (DCIS), the presence of comedo necrosis reportedly predicts for higher rates of post-operative recurrence. To examine the role of programmed cell death (apoptosis) in the aetiology of the cell death described as comedo necrosis, we studied 58 DCIS samples, using light microscopy, for morphological evidence of apoptotic cell death. The percentage of apoptotic cells (apoptotic index, AI) was compared between DCIS with and without evidence of 'comedo necrosis' and related to the immunohistochemical expression of the anti-apoptosis gene bcl-2, mitotic index (MI), the cellular proliferation antigen Ki67, nuclear grade and oestrogen receptor (ER) status. AI was significantly higher in DCIS samples displaying high-grade comedo necrosis than in low-grade non-comedo samples: median AI = 1.60% (range 0.84-2.89%) and 0.45% (0.1-1.31%) respectively (P < 0.001). Increasing nuclear grade correlated positively with AI (P < 0.001) and negatively with bcl-2 expression (P = 0.003). Bcl-2 correlated negatively with AI (P = 0.019) and strongly with ER immunoreactivity (P < 0.001). Cellular proliferation markers (MI and Ki67 immunostaining) correlated strongly with AI and were higher in comedo lesions and tumours of high nuclear grade (P < 0.001 in all cases). Thus, apoptosis contributes significantly to the cell death described in ER-negative, high-grade DCIS in which a high proliferative rate is associated with a high apoptotic rate. It is likely that dysregulation of proliferation/apoptosis control mechanisms accounts for the more malignant features typical of ER negative comedo DCIS.     

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

The N-terminal domain (1-318 amino acids) of mouse NFkappaB (p65) has been purified to homogeneity from the soluble fraction of Escherichia coli cells expressing this protein. Its complex with a full-length ikappaB-alpha (MAD3, 1-317 amino acids) molecule was generated by binding the E. coli-derived ikappaB-alpha to the purified NFkappaB and purifying the complex by sequential chromatography. The stoichiometry of NFkappaB to ikappaB in the complex was determined to be 2 to 1 by light scattering and SDS-polyacrylamide gel electrophoresis. The secondary structure of the NFkappaB (p65) determined by Fourier-transform infrared (FTIR) spectroscopy is in good agreement with that of the p50 in the crystal structure of the p50/DNA complex, indicating that no significant structural change in NFkappaB occurs upon binding of DNA. The FTIR spectrum of the NFkappaB/ikappaB complex indicates that its secondary structure is composed of 17% alpha-helix, 39% beta-strand, 18% irregular structures, and 26% beta-turns and loops. By comparing these data to the FTIR data for NFkappaB alone, it is concluded that the ikappaB (MAD3) in the complex contains 35% alpha-helix, 27% beta-strand, 22% irregular structures, and 16% beta-turns and loops. Circular dichroism (CD) analysis of a shorter form of ikappaB (pp40) indicates that it contains at least 20% alpha-helix and that the ikappaB subunit accounts for nearly all of the alpha-helix present in the NFkappaB/ikappaB complex, consistent with the FTIR results. The stabilities of NFkappaB, ikappaB, and their complex against heat-induced denaturation were investigated by following changes in CD signal. The results indicate that the thermal stability of ikappaB is enhanced upon the formation of the NFkappaB/ikappaB complex.     

Comparative genomic hybridisation of ductal carcinoma in situ of the breast: identification of regions of DNA amplification and deletion in common with invasive breast carcinoma

Comparative genomic hybridisation has been used to map copy number changes in nine cases of ductal carcinoma in situ of the breast obtained from wax-embedded archive material. A wide variety of abnormalities were detected including gain of regions of 1q, 17q, 19q, 20p and 20q and loss on 13q, 14q, 17p, 16q and 22q. Amplification of areas on 10p, 8q and 20q were also observed. Chromosomal alterations were more frequent in higher grade DCIS and closely resemble those previously detected in invasive breast cancer using the same technique. These data provide strong molecular support for the view that DCIS is a precursor lesion of invasive breast carcinoma.     

Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma

The increased use of screening mammography has resulted in a marked increase in detected cases of ductal carcinoma in situ (DCIS) of the breast since the early 1980s. In 1993, there were an estimated 23,275 newly diagnosed cases of DCIS in the United States, of which 4,676 were in women aged 40-49. DCIS accounted for 14.7% of all newly diagnosed breast cancers in women aged 40-49 in 1993, and perhaps 40% of all mammographically detected breast cancers in this age group are DCIS. Among women aged 40-49, an estimated 1,890 mastectomies and 2,707 lumpectomies (with or without radiation) were performed for DCIS in 1993. There is an urgent need to better understand the relationship of mammographically detected DCIS to invasive and potentially life-threatening breast cancer. Better information about the appropriate treatment of DCIS is also needed to reduce the confusion and uncertainty many women and their physicians currently experience in the face of a DCIS diagnosis. For the present, women considering screening mammography should be told the likelihood of being diagnosed with DCIS and that only some DCIS cases may be clinically significant but almost all will be treated surgically.     

A practical approach to breast ductal carcinoma in situ and tumors with an extensive intraductal component

Seventy-two patients were admitted in a multicentre trial with the purpose of assessing the clinical efficacy and safety of the hormonal control and tolerance of leuprolide acetate in a once-a-month depot injection formulation for the treatment of disseminated prostate cancer. During a 1-year follow-up, there were ten withdrawals for different reasons. At baseline and at 6 months of treatment the following parameters were evaluated: clinical examination, routine blood analysis, PAP, PSA, LH and testosterone, as well as bone scan. LH and testosterone determinations were repeated at 2, 4, 8, 12, 16, 20 and 24 weeks. Testosterone reached castration levels within the second week and was maintained until the end of the study. In agreement with the NPCP criteria, 65 patients were assessed as: complete response 3%, partial response 40%, disease stabilization 36%, and progression 21%. In summary, a once-a-month injection of leuprolide acetate offers a safe and effective alternative to surgical castration.     

Loss of heterozygosity on chromosome 11p15 during histological progression in microdissected ductal carcinoma of the breast

Two enone reductases catalyzing irreversibly the enantioselective reduction of alpha,beta-unsaturated carbonyls have been purified 165-fold and 257-fold, respectively, from the cytosolic fraction of Saccharomyces cerevisiae by means of streptomycin sulfate treatment, Sephadex G-25 filtration, DEAE-Sepharose CL-6B chromatography, blue Sepharose CL-6B chromatography and Superdex 200 preparation-grade filtration. One enzyme (E I) was NADPH-dependent, showed a molecular mass of 75 kDa and decomposed under denaturing electrophoretic conditions into two subunits of 34 kDa and 37 kDa. The other enzyme (E II) was NADH linked and the molecular mass estimated by means of Superdex 200 preparation-grade filtration, was 130 kDa. The enzyme decomposed into subunits of 56 kDa and 64 kDa on SDS/PAGE. Both enzymes were most active at pH 4.8 and accepted 1-octen-3-one, 1-hexen-3-one, 3-alken-2-ones, 4-alken-3-ones, 2-cyclohexen-1-ones, 2-alkenals, 2,4-alkadienals, 2-phenyl-2-alkenals, and 2-alkyl-2-alkenals as substrates. Both enzymes showed their highest activities with 1-hexen-3-one and 1-octen-3-one, respectively. The Km values for 1-octen-3-one were estimated as 0.54 mM (E I) and 0.20 mM (E II), respectively. Both enzymes catalyzed the enantioselective reduction of cis- and trans-2-phenyl-2-butenal into (R)-2-phenylbutanal.     

Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up

OBJECTIVE: To identify the independent and differential diagnostic and symptom correlates of suicidal ideation and suicide attempts and determine whether there are gender- and age-specific diagnostic profiles. METHOD: The relationships between suicidal ideation, suicide attempts, and psychiatric disorders were examined among 1,285 randomly selected children and adolescents, aged 9 to 17 years, of whom 42 had attempted suicide and 67 had expressed suicidal ideation only. Youths and their parents were interviewed as part of the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, using the Diagnostic Interview Schedule for Children Version 2.3 (DISC-2.3). RESULTS: Logistic regression analyses indicated that mood, anxiety, and substance abuse/dependence disorders independently increased the risk of suicide attempts, after controlling for sociodemographic characteristics. There was no significant independent contribution of disruptive disorders to suicide attempts, although its association with suicidal ideation was significant. Substance abuse/dependence independently differentiated suicide attempters from ideators. Noncriterion symptoms that remained significant predictors of suicide risk, after adjusting for psychiatric disorder, included panic attacks and aggressiveness. Perfectionism did not significantly increase suicide risk after adjusting for psychiatric disorder. The association of specific disorders and noncriterion symptoms with suicidality varied as a function of gender and age. CONCLUSION: A monolithic diagnostic risk profile for suicidality, ignoring gender- and age-specific risks, is inadequate. The contribution of substance abuse/dependence in the escalation from suicidal thoughts to suicide attempts is underscored.     

A comparative study of metastatic patterns of ductal and lobular carcinoma of the breast from two matched series (376 patients)

Five studies comparing metastatic patterns of lobular and ductal carcinoma have reported conflicting results. These results are based on the evaluation of heterogeneous groups, without taking clinical differences into account. The aim of this clinical study is to compare metastatic patterns of matched ductal and lobular carcinomas. One hundred eighty-eight lobular carcinomas were matched with 188 ductal carcinomas who showed identical ages, menopausal status, TNM, and dates of treatment. Hepatic, lung and brain metastases are more frequent in ductal carcinoma. Metastases to the gastrointestinal system, gynecologic organs, and peritoneum are more characteristic of lobular carcinoma. Life table analysis of overall and disease free survival shows no significant differences. The metastatic patterns of ductal and lobular carcinomas are different, and physicians should be aware that the classical staging of the breast cancer is not fit to lobular carcinoma. fit to lobular carcinoma. Could we define patients presenting high metastatic risks? Could we use CA. 125, sonography, laparoscopy in the staging? Should we change the whole therapeutic approach of lobular carcinoma?     

Paget's disease of the breast in a man without underlying breast carcinoma

A case of histologically confirmed Paget's disease of the breast in a 72 year old man, without underlying breast carcinoma, is reported. This report raises questions about the pathogenesis of this condition and suggests that Paget's disease is an independent, intraepidermal carcinoma rather than a direct extension of intraductal carcinoma of the breast to the nipple and areola.     

Metastasis of a sigmoid carcinoma to the breast

Breast metastases are usually a rare event. We present the case of a 42-year-old patient with a primary carcinoma of the sigmoid metastatic to the breast and metastasis in the liver as well. Although seldom, it is important that metastatic cancer to the breast be differentiated from primary breast carcinoma as both the treatment and the prognosis differ significantly.