UMLS:C0027627 - FACTA Search

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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-FU is a cycle-specific S-phase-dependent drug with a short half life of 10-20 min. There is therefore a rationale for its use in long-term continuous infusional therapy, with doses of up to 300 mg/m2 per day proving feasible for prolonged periods. The schedule is active in patients with heavily pre-treated breast cancer, with responses in up to 53% (overall 29%). At the Royal Marsden Hospital we have evaluated infusional 5-FU 200 mg/m2 per day for up to 6 months in combination with 3-weekly bolus epirubicin (E) 60 mg/m2 and cisplatin (C) 60 mg/m2 (infusional ECF) as pre-operative/neo-adjuvant treatment in 123 patients with operable breast cancer greater than 3 cm (median 6 cm), initially in a phase II study of 50 patients and subsequently as part of a randomised phase III trial. One hundred and eighteen (96%) have achieved objective tumour responses, with 67 (57%) achieving CR. The 5-year actuarial survival rate is 78% and the local recurrence rate without associated metastatic disease 12%. The pathological complete remission (CR) rate was 16%, with a further 5% having residual DCIS only. Pathological CR but not clinical CR is an independent predictor for disease-fee survival. The Royal Marsden is now conducting two multicentre randomised trials of infusional ECF: (i) versus conventional AC (adriamycin cyclophosphamide) as pre-operative/neo-adjuvant chemotherapy, with 376 patients so far randomised towards a target of 400; and (ii), more recently, a similar adjuvant trial versus conventional FEC (5-FU, epirubicin, cyclophosphamide), with 168 patients so far randomised. These trials will determine whether encouraging phase II activity with continuous infusional chemotherapy translates eventually into real survival benefit for patients with early breast cancer.
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PMID:Continuous infusional chemotherapy for early breast cancer: the Royal Marsden Hospital experience. 992 69

Postmastectomy radiation therapy may be recommended for patients with a high risk for local recurrence after mastectomy for ductal carcinoma in situ (DCIS). However, long-term outcomes after postmastectomy radiation therapy are not well described. This study was performed to determine long-term outcomes in patients treated with radiation therapy after mastectomy for DCIS. The authors reviewed the records of all patients with breast cancer treated with postmastectomy radiation therapy between 1978 and 1992. Of 287 total patients treated, three (1%) were for DCIS. These three patients had diffuse microcalcifications on screening mammography. The reason for postmastectomy radiation therapy was a potentially increased risk for local recurrence because of a positive resection margin after mastectomy for DCIS. Surgery consisted of a total mastectomy (n = 2) or a modified radical mastectomy (n = 1). Radiation therapy consisted of 4275-5000 cGy to the chest wall in 200-225 cGy fractions. The energy used was 6-MV photons (n = 2) or 15-MV photons (n = 1). No regional nodal irradiation was used. Bolus was applied to the chest wall every other day in one of the three patients. One patient was treated with a scar boost after chest wall irradiation (boost dose, 1000 cGy; total dose, 5275 cGy). The median age for the three patients was 46 years (range, 41-68 years). No patient received adjuvant chemotherapy or hormonal therapy. With a minimum follow-up of 7.1 years (median, 7.4 years; range, 7.1-19.4 years), no local-regional recurrence or evidence of metastatic disease developed in any of the patients. No long-term complication from radiation therapy was noted, and no contralateral breast cancer developed. All patients were alive and free of relapse at the last follow-up. The use of radiation therapy in this group of three patients has shown no evidence of relapse with a minimum of 7.1 years of follow-up. The authors conclude that radiation therapy may be indicated after mastectomy for DCIS to reduce the risk of recurrence for high-risk patients.
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PMID:Long-term outcome after postmastectomy radiation therapy for the treatment of ductal carcinoma in situ of the breast. 1036 24

MUC1 mucin is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of normal glandular epithelia. In many human adenocarcinomas, this protein is up-regulated and/or underglycosylated, and its expression changes from apical to the entire cell membrane. It is thought that entire cell membrane expression of MUC1 reduces cell-cell and cell-extracellular matrix interactions and therefore may facilitate invasive growth and development of metastases. In this study, we determined immunohistochemically the expression of normal and underglycosylated MUC1 in normal breast tissue (n = 8) and in a spectrum of breast lesions, including usual ductal hyperplasia (n = 23), atypical ductal hyperplasia (n = 7), and ductal carcinoma in situ (DCIS) (n = 22). We used 4 monoclonal antibodies; 115D8 is directed to a glycopeptide, the other 3 to the peptide core of the molecule, of which 139H2 is not affected by the degree of glycosylation of MUC1, whereas SM3 and VU-4-H5 stain only underglycosylated forms. All cases showed apical positivity for 115D8 and 139H2. Entire cell membrane expression of fully (normal) glycosylated MUC1 was mainly found in DCIS lesions. Apical staining of SM3 was found in 38% of normal cases and 60% of the ductal lesions with no difference between the different subgroups. Apical staining of VU-4-H5 was found more often in DCIS (27%) than in normal tissue or ductal hyperplasia (3%). Membrane expression of underglycosylated MUC1 was found only in poorly differentiated DCIS. In conclusion, aberrant expression of MUC1, i.e., on the entire cell membrane and/or underglycosylated forms, can be found in ductal hyperplasia with atypia and especially in DCIS of the breast. This finding implies that these lesions with aberrant expression are at higher risk for developing subsequent invasive breast carcinoma.
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PMID:Aberrant expression of MUC1 mucin in ductal hyperplasia and ductal carcinoma In situ of the breast. 1050 21

A case of primary breast cancer showing differentiation to malignant melanoma is reported. To obtain insight into the clonal relationship between the two components of the tumor, polymerase chain reaction-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 1q, 3q, 4q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, and 18q with microdissected tissues of both components was performed in addition to histologic, histochemical, immunohistochemical, and ultrastructural techniques. The tumor consisted of a combination of carcinoma and melanoma with morphologic transition. Metastases in the lymph nodes and thoracic spinal bone marrow showed dual tissue structure. One of the metastatic lung tumors showed melanomatous tissue structure. The abundant pigment in the cells was positive for Fontana-Masson staining and bleached with potassium permanganate. The carcinoma component was positive for epithelial membrane antigen and CA19-9, but the melanoma component was negative. Conversely, the melanoma component was positive for HMB45 and vimentin, but the carcinoma component was negative. Electron microscopic analysis showed premelanosomes and melanosomes in the melanoma component. Microsatellite analysis showed the same genetic alterations with loss of heterozygosity on chromosome arms 1p, 3q, 4q, 6q, 9p, 10q, 11q, 13q, 16q, 17p, and 17q in in situ, invasive, and metastatic foci. We concluded that the carcinoma and melanoma components had arisen from the same clone and that this breast carcinoma might have diverged to aberrant malignant melanoma through multiple genetic alterations in the early period of ductal carcinoma in situ.
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PMID:Breast carcinoma diverging to aberrant melanocytic differentiation: a case report with histopathologic and loss of heterozygosity analyses. 1052 31

Although ductal carcinoma in situ (DCIS) of the breast is accepted as a potential precursor lesion for invasive ductal cancer (IDC), the critical genetic events associated with the tumor progression remain unknown. Since some extensive DCIS may show a small focus of IDC, these cases seem to be particularly suitable to investigate the primary abnormalities that determine the progression from in situ to early invasive cancer. We combined laser-microdissection with degenerative oligonucleotide-primed PCR (DOP-PCR) and comparative genomic hybridization (CGH) to detect copy number changes in 7 cases of extensive (>4 cm) DCIS with 1 small adjacent invasive focus. In 3 of the cases, single lymph node metastases (LN) were already present and were also investigated. Analysis of DCIS, IDC and LN components in the same patients revealed several consistent chromosomal changes present at all 3 sites: 1q, 7q, 8q, 16, 17, 19, 20q, 21q and 22q, the most frequent losses on 4q, 11q and 13q. DNA gain on 3p and 12q were more frequently found in IDC than in DCIS, suggesting the presence of proto-oncogenes activated during the progression to invasive cancer on these regions. Using paired analysis, resemblence of alterations found in DCIS and IDC could be quantified (odds ratio 7.0, p< or = 0.01). Gains on 6p, 10q, 14q and 15q and losses on 9p were identified in DCIS and IDC but not in LN, which may, therefore, represent early events in the carcinogenic process. Additional losses were found in the LNs on 2q, 3q, 5q, 6q, 12q and 16q. CGH results on chromosome 1 and 20 were confirmed by FISH and on chromosomal region 9p by microsatellite analyses. Our findings strongly underline the precursor status of high-grade DCIS, in which most of the chromosomal changes identified in IDC are already present. However, although the early stages of breast cancer, i.e., DCIS and the small foci of IDC were mainly characterized by DNA gains, the progression to metastatic tumor (LN) must have involved additional DNA losses on several regions.
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PMID:Extensive ductal carcinoma In situ with small foci of invasive ductal carcinoma: evidence of genetic resemblance by CGH. 1058 88

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast. We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months. Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma. We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."
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PMID:Sarcomatoid salivary duct carcinoma of the parotid gland. 1068 35

This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a 'paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the pro
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PMID:From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. 1071 Dec 39

The purpose of the present paper was to evaluate the characteristics and outcomes of male breast cancer patients seen for adjuvant therapy at a single institution. A retrospective review of computerized records in the Departments of Medical and Radiation Oncology at the Royal Prince Alfred Hospital (RPAH) was undertaken. Between 1983 and 1996, 24 men were referred for treatment of breast cancer. Of these, 19 had localized breast cancer, four had metastatic disease and one had ductal carcinoma in situ (DCIS). The median age was 57.5 years (range: 26-78) and median follow-up was 6.2 years (range: 0.6-36). Pathological staging was performed. Survival was assessed using actuarial life table analysis. Of the 19 patients who presented with localized disease, there were 12 T1, five T2 and two T4 cancers. Eleven patients had axillary lymph node involvement. Ten patients were oestrogen receptor (ER) positive, two patients were ER negative and seven patients had unknown receptor status. All patients underwent surgery. Eleven patients received radiotherapy. The median dose and dose per fraction were 50 Gy and 2 Gy, respectively. Adjuvant systemic therapy was delivered to 10 patients, of whom nine were node-positive. Four patients received chemotherapy alone, three patients received chemotherapy and tamoxifen, and three patients received tamoxifen only. Seven patients relapsed (one local, five distant, one both). Of the two patients with local relapses, one had received radiotherapy. Of the distant failures, four of six patients had no systemic therapy. There were only two node-positive patients who were not given systemic treatment and both relapsed. Median survival in all patients with invasive cancer was 7.5 years, and in those with localized disease it was 7.6 years. The median survival of node-positive patients was 3.8 years. In node-negative patients the median survival had not been reached at a median follow-up of 6.2 years. The majority of patients (12/14) with known receptor status were ER+, a finding that parallels those of other studies. Local control rates were 88% (7/8) in patients who had mastectomy alone and 91% (10/11) in those patients receiving adjuvant radiotherapy. Systemic therapy was found to be beneficial in patients with node-positive disease. Chemotherapy was administered more frequently than hormonal therapy. The median survivals were consistent with those reported in other series.
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PMID:Carcinoma of the male breast: a review of adjuvant therapy. 1090 73

The purpose of this study was to determine factors associated with the incidence of axillary lymph node metastases (ALNM) in T1 tumors and cases in which axillary dissection could be omitted. Data from 195 patients with T1 primary invasive breast cancer (size < or = 2 cm) who underwent either mastectomy or wide local excision of the tumor and axillary dissection were reviewed. ALNM was found in 59 of 195 patients with T1 tumors (30.3%). Tumor size was found to be the only independent predictor of ALNM, having a directly analogous relationship with the probability of invaded nodes: T1a (< or = 5 mm) tumors had 0 per cent ALNM, whereas T1b (5 mm < T1b < or = 10 mm) and T1c (10 mm < T1c < or = 20 mm) tumors had 25.7 per cent and 33.8 per cent ALNM respectively. Among the other factors studied (patient age, tumor site, hormone receptor status, histologic type, and grade of the tumor) only the histologic grade of the tumor cells appeared to correlate with the incidence of lymph node involvement, but this was not statistically significant. In conclusion only tumor size has statistically significant correlation with the incidence of ALNM. Routine axillary dissection could be omitted only in patients at minimal risk of ALNM (ductal carcinoma in situ and T1a) and when treatment decisions were not influenced by lymph node status (e.g., elderly patients with clinically negative axilla). Axillary dissection (at least levels I and II) should be performed in all cases with primary invasive breast cancer with tumor size > 5 mm.
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PMID:Factors affecting axillary lymph node metastases in patients with T1 breast carcinoma. 1109 7

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.
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PMID:Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion. 1110 51

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