Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS)

PURPOSE: The role of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS) is controversial. In particular, there is little data for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographic calcifications < or = 2.5 cm, negative resection margins, negative postbiopsy mammogram). This study reports outcome of conservative surgery and radiation for mammographically detected DCIS with an emphasis on results in patients considered candidates for excision alone. METHODS AND MATERIALS: From 1983 to 1992, 110 women with mammographically detected DCIS (77% calcifications +/- mass) and no prior history of breast cancer underwent needle localization and biopsy with (55%) or without a reexcision and radiation. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The most common histologic subtype was comedo (54%), followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven percent of patients with calcifications only had a negative postbiopsy mammogram prior to radiation. Radiation consisted of treatment to the entire breast (median 50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40 Gy. RESULTS: With a median follow-up of 5.3 years, three patients developed a recurrence in the treated breast. The median interval to recurrence was 8.8 years and all were invasive cancers. Two (67%) occurred outside the initial quadrant. The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two patients. There were too few failures for statistical significance to be achieved with any of the following factors: patient age, family history, race, mammographic findings, location primary, pathologic size, histologic subtype, reexcision, or final margin status. However, young age, positive or close margins, and the presence of a mass without calcifications had a trend for an increased risk of recurrence. There were no recurrences in the subset of 16 patients who would be candidates for surveillance by Lagios' criteria. CONCLUSION: For selected patients, conservative surgery and radiation for mammographically detected DCIS results in a low risk of recurrence in the treated breast and 100% 5- and 10-year cause-specific survival. Improved mammographic and pathologic evaluation results in better patient selection and reduces the risk of the subsequent appearance of DCIS in the biopsy site. The identification of risk factors for an ipsilateral invasive breast recurrence is evolving.     

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.     

Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls

Leptin reflects the amount of energy stores, regulates energy balance and is associated with circulating levels of reproductive hormones and insulin-like growth factor-I (IGF-I). Breast cancer has also been associated with obesity, reproductive hormones and circulating IGF-I levels. To determine whether leptin is involved in the etiology of breast cancer, we compared serum leptin levels in 83 cases of pre-menopausal carcinoma in situ of the breast and 69 healthy controls recruited in Massachusetts. Serum leptin levels were 13.69 + 1.3 ng/ml in cases and 16.03 + 1.7 ng/ml in controls. Data were also analyzed using multiple logistic regression with adjustment for known risk factors for the development of breast cancer as well as anthropometric, demographic and hormonal variables, including estradiol, prolactin, IGF-I and IGF-binding protein-3. Odds ratios were 1.75 (95% CI, 0.73-4.21) for the second control-defined tertile and 1.54 (0.46-5.16) for the third control-defined tertile relative to the first. Thus, leptin does not appear to increase the risk of pre-menopausal breast cancer in situ substantially.     

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.     

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.     

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.     

Ductal carcinoma in situ: introduction of the concept of ductal intraepithelial neoplasia

The current definition, diagnostic criteria, grading, and approach to assessment of extent of ductal carcinoma in situ (DCIS) are presented. The problem areas, particularly the difficulties in separating low-grade DCIS from atypical intraductal hyperplasia (AIDH), accurate assessment of size and/or extent of DCIS, and their impact on patient management are critically reviewed. On the basis of the route of progression of DCIS, recently confirmed by three-dimensional reconstructed models, an optimal and simple approach to uniform excision, orientation, and processing of biopsy samples is presented. Emphasis is placed on the role of intraductal proliferative lesions (IDH, AIDH, and DCIS) as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. It is proposed that these proliferations should be classified as "mammary intraepithelial neoplasia, ductal type" or as "ductal intraepithelial neoplasia" (DIN); the rational for the application of this classification system is provided. This approach obviates the current separation of AIDH and low-grade DCIS into two very drastically different categories of cancer and non-cancer without interfering with appropriate management of the various lesions. The DIN classification is presented in a simple translational table, along with the current terminology for various lesions.     

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.     

Ductal carcinoma in situ of the breast

PURPOSE: The increasing incidence and biological heterogeneity of ductal carcinoma in situ (DCIS) of the breast have made the management of this entity challenging and controversial. This paper reviews data on the natural history of the disease and results obtained with various management approaches. DATA SOURCES: Computerized MEDLINE search of articles related to DCIS published since 1966. STUDY SELECTION: Randomized trials were given higher value; however, because these were relatively scarce, retrospective studies and data published in abstract form were also included. DATA EXTRACTION: The authors reviewed all sources critically. No formal statistical calculations were made. DATA SYNTHESIS: The incidence of DCIS is increasing, and a greater proportion of diagnoses are being made in asymptomatic patients. No data from randomized trials compare mastectomy and breast-conserving therapy for the treatment of DCIS. A large randomized trial comparing lumpectomy with lumpectomy plus radiotherapy showed lumpectomy plus radiotherapy to be effective for management of this disease. The presence of comedo necrosis and surgical margin status are frequently used as predictors of subsequent recurrence, although this practice is controversial. The risk for in-breast recurrence at 5 years after lumpectomy and radiotherapy is approximately 8%. With more refined molecular analysis, the relation of DCIS to invasive breast cancer will be better defined. CONCLUSIONS: Treatment strategies for DCIS have evolved, and lumpectomy followed by radiotherapy is an appropriate alternative for most patients. The use of lumpectomy alone in selected patients remains controversial.     

Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma

Heterochromatin protein 1 (HP1) of Drosophila and its homologs in vertebrates are key components of constitutive heterochromatin. Here we provide cytological evidence for the presence of heterochromatin within a euchromatic chromosome arm by immunolocalization of HP1 to the site of a silenced transgene repeat array. The amount of HP1 associated with arrays in polytene chromosomes is correlated with the array size. Inverted transposons within an array or increased proximity of an array to blocks of naturally occurring heterochromatin may increase transgene silencing without increasing HP1 labeling. Less dense anti-HP1 labeling is found at transposon arrays in which there is no transgene silencing. The results indicate that HP1 targets the chromatin of transposon insertions and binds more densely at a site with repeated sequences susceptible to heterochromatin formation.     

Clinical problems of the breast carcinoma in situ

The results of diminution mammoplasties are reported. From 1972 to 1974, 70 diminution mammoplasties according to Str?mbeck were carried out. Indication for the operation was hypertrophy of the breasts with side effects of morbid value. In 47 patients side effects of the body posture were the leading indication. In 23 patients, psychosocial problems were the indication. Only patients with side effects of morbid value were considered to be sufficiently motivated to tolerate the total stress of the operation and the possible post-operative complications. The technical problems of the operation and the post-operative complications are described. 43 patients were followed up at least one year after the operation. In 36 patients the pre-operative complaints were alleviated by the operation. In 7 patients there was improvement. No patient had continuing pre-operative complaints. The mentally depressed and physically and psychologically in their relationship to their environment handicapped patients became usually more satisfied by the operation. Diminution mammoplasties are recommended for the operative treatment of hypertrophy of the breast with side effects of morbid value.     

Lobular carcinoma in situ of the breast: results of a radiosurgical conservative treatment

From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by mammography. Twelve women also received tamoxifen at 20 mg/day for two years. With a median follow-up of 88 months, no local or regional recurrences have been recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one metachronous). In the literature, only eight other cases of LCIS were treated by lumpectomy and radiation therapy, but without details and data on long-term results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred in about 15% of the cases. Thus, the classical radiosurgical association should represent an interesting alternative both for biopsy alone and radical surgery until now only proposed to treat LCIS.     

Nonselective debridement and antimicrobial cleansing of a venting ductal breast carcinoma

Supracondylar femur fractures above a total knee replacement are rare injuries that may be challenging to treat. We present a case of an elderly woman whose supracondylar femur fracture was not deemed amenable to conventional treatment. This patient underwent fixation of her femur fracture above a total knee replacement using an Ilizarov external fixator. The fixator was removed at 10 weeks, at which time the fracture was solidly healed. At the most recent follow-up, the patient is 19 months postinjury. She is fully weight bearing without walking aids and has a knee range of motion of 0 degree to 110 degrees.     

Case-control study of colorectal carcinoma in situ and cancer in relation to cigarette smoking and alcohol use (Japan)

A case-control study was performed in order to examine the relation of cigarette smoking and alcohol use to colorectal carcinoma in situ and cancer, separately. Study subjects consisted of 129 colorectal carcinoma in situ cases, 66 colorectal cancer cases, and 390 controls recruited from health check-up examinees in Tokyo from January 1991 to March 1993. Smoking status and alcohol habit were ascertained from a self-administered questionnaire. Both cumulative cigarette smoking and current smoking status were associated significantly with an increased risk of carcinoma in situ. A statistically nonsignificant increase in the risk of colorectal cancer was noted only among those with the heaviest exposure category of these measures of smoking. The cumulative exposure to cigarette smoking within recent 20 years was associated significantly with an increased risk of carcinoma in situ, whereas smoking until 20 years before the diagnosis was associated significantly with an increase of cancer risk. A significant and positive association was observed between cumulative alcohol drinking and colorectal cancer. These findings suggest that cigarette smoking may act as an initiator in colorectal carcinogenesis and also provide weak evidence that alcohol drinking is related to an increased risk of colorectal cancer.