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

Breast cancer in African Americans in the US is more aggressive and has a worse outcome than breast cancer in Caucasians. Although the incidence of breast cancer among US whites is higher than among blacks, the mortality rates for blacks are much higher. Breast cancer in blacks is also associated with a more advanced stage at presentation and pathologically aggressive tumors commonly exhibiting estrogen receptor negativity, higher S-phase fractions, and higher numbers of involved lymph nodes. This paper reviews some of the genetic factors that have been shown to be associated with a difference in breast cancer outcome between African Americans and Caucasians in the US such as the BRCA1 and BRCA2 genes, p53 mutations, UGT1A1 gene polymorphisms, and HER-2/neu gene amplifications/overexpression.
Cancer Metastasis Rev 2003 Mar
PMID:Racial differences in genetic factors associated with breast cancer. 1271 36

It is not known if the behaviour of hereditary breast cancer (HBC) differs from that of sporadic breast cancer (BC). The aim of the present study was to analyze clinical-pathological characteristics in patients with BRCA1/2-mutation associated to BC. These data could be useful in the management of HBC. This study includes 17 patients with BC in whom a germ-line BRCA1/2-mutation was diagnosed. The patients were from 10 different families, and four patients had no family history of BC or ovarian cancer (OC). The study of mutations was with the protein truncation test (exon 11 for BRCA1, exons 10 and 11 for BRCA2) and sequencing (the rest of exons). At diagnosis the mean age was 37 years (28-54). Only 3/17 patients presented with involvement of axillary nodes; no patient was diagnosed with metastatic disease. All cases were infiltrating ductal carcinoma; two of them were medullary carcinoma. Histological grade was available in 13/17 cases, with grade III being the most frequent (12/13). Hormonal receptors were negative in 8/10 patients. The mean follow-up was 129 months (23-223). There were three local recurrences at 17, 108 and 151 months; and two distant relapses at 15 months (complete remission) and 92 months. There were three diagnosed contralateral BC. Hereditary breast cancer has malignant pathological features, but the clinical behaviour may be less aggressive than sporadic breast cancer in the same age group.
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PMID:Clinical and pathological findings of BRCA1/2 associated breast cancer. 1496 59

To increase awareness of the possible coexistence of an ovarian and breast carcinoma in a BRCA1 mutation carrier, we describe a patient with primary ovarian cancer who developed distant metastases after 3 years and again after 6 years. Surprisingly, at that time an occult breast carcinoma was identified to be the origin of the 2 metastatic locations as confirmed by molecular analysis. Eventually the patient could be treated accordingly.
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PMID:A metastasis of an adenocarcinoma in a BRCA1 mutation carrier, a diagnostic problem not solved by morphology alone. 1513 40

Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.
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PMID:Secretory breast cancer in a 7.5-year old boy. 1545 4

Women from families with multiple cases of breast and ovarian cancer, specifically those who carry cancer-associated mutations of BRCA1 or BRCA2 are at increased life-time risk for peritoneal carcinoma, even after previous surgery to remove the ovaries, fallopian tubes and uterus. Hereditary breast-ovarian cancer (HBOC) syndrome and the associated BRCA1 and BRCA2 mutations are particularly prevalent in women of Jewish lineage, and specific BRCA1 and BRCA2 germline mutations have been linked with peritoneal carcinoma and HBOC syndrome in Jewish populations, especially those of Ashkenazi descent. This review presents the currently available data and looks forward toward further and better understanding of peritoneal carcinoma in women with inherited susceptibility. Over 90% of peritoneal cancer in patients from HBOC syndrome kindreds and associated with BRCA1 and BRCA2 mutations are serous carcinomas, which is equivalent with the proportion of ovarian cancers that are serous carcinomas in similar patients. The best indications are that while many peritoneal carcinomas in genetically susceptible women may arise directly from malignant transformation of the peritoneum, others might represent metastases from primary ovarian or fallopian tube carcinomas. Although the incidence of borderline ovarian tumors may not be increased in HBOC syndrome kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, these individuals could be susceptible to malignant transformation of borderline lesions of the ovaries and peritoneum. Moreover, recent reports raise the question of possibly increased risk in Jewish carriers of germline BRCA1 mutations for uterine papillary serous carcinoma, which could be the source of metastasis to the peritoneum in some cases. The penetrance of cancer-associated BRCA1 mutations for ovarian cancer is estimated to be 11%-54%, and for BRCA2 mutations the penetrance for ovarian cancer is 11%-23%. So far, available screening methods appear to be insufficient for early detection of many ovarian cancers. Prophylactic oophorectomy has been found to reduce the risk for ovarian cancer in women from HBOC kindreds and those who carry cancer-associated BRCA1 and BRCA2 mutations, leaving a residual risk for peritoneal carcinomatosis of well less than 5%. Therefore, surgical removal of the ovaries, fallopian tubes and uterus, after child-bearing has been completed and by early in the fifth decade of life, are appropriate prophylactic procedures in women whose genetic susceptibility puts them at increased risk for cancers of mullerian tract origin, including ovarian and fallopian tube carcinomas and possibly serous carcinoma of the uterus. Hysterectomy, as well as salpingo-oophorectomy, removes the gynecologic organs targeted for malignant transformation in genetically susceptible women and simplifies decisions regarding hormone replacement therapy and chemical prophylaxis and treatment of breast cancer. Unless a transabdominal operative approach is otherwise indicated, laparoscopic-assisted transvaginal techniques are well suited for intra-abdominal exploration, cytology, biopsies and prophylactic salpingo-oophorectomy and hysterectomy in women with hereditary susceptibility to gynecologic cancer.
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PMID:Peritoneal carcinoma in women with genetic susceptibility: implications for Jewish populations. 1551 51

Breast ducts contain two types of epithelial cells, inner luminal cells and outer basal/myoepithelial cells. These cells can be distinguished by their immunophenotype. Cytokeratins (CKs) 8 and 18 are expressed in the luminal layer, whereas CK5/14 and the transcription factor p63 characterize the basal epithelial layer. We studied a population-based cohort of 288 sporadic ductal invasive cancers and found 9% positive for CK5/14 and 4% positive for p63. Using a highly sensitive polymer-based immunohistochemical staining, all sporadic tumors were positive for the luminal CK8/18, including those positive for CK5/14. Pairs of primary tumors and metastases (n = 38) were always concordant for CK5/14 expression. The majority of the CK5/14-positive cases were of histologic grade III (P = 0.0007) and steroid hormone receptor negative (P < 0.0001). CK5/14 expression was inversely associated with HER-2 oncogene amplification, but only in the subgroup of estrogen receptor-negative tumors (P = 0.007). In a separate set of 42 hereditary breast cancers, the majority (78%) of the BRCA1-associated tumors, but only one of 15 BRCA2-associated tumors was positive for CK5/14. In contrast to sporadic CK5/14-positive tumors, BRCA1-associated tumors displayed less intense CK8/18 staining, including some truly CK5/14-positive CK8/18-negative cases. These results suggest that CK5/14-positive sporadic breast cancers arise from glandularly committed progenitor cells rather than true CK8/18-negative basal cells.
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PMID:Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors. 1599 Aug 99

The aim of this study was to evaluate clinicopathological characteristics and immunophenotypes of simultaneous bilateral adenocarcinomas of the breast and their axillary metastases. Immunohistochemical analysis and in situ hybridization were performed using formalin-fixed/paraffin-embedded tissues. In total, 15 primary and 9 metastatic tumors from 8 patients were evaluated. The expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), Ki 67, p53, bcl-2, and bax were evaluated by immunohistochemistry. Her2 gene amplification was evaluated by chromogenic in situ hybridization (CISH). Four patients were younger that 40 years of age (mean 47 years). Six patients had pleomorphic lobular carcinoma in 1 breast. Four of these had invasive ductal carcinoma in the contralateral breast. One patient had atypical medullary carcinoma in both breasts and 1 patient had atypical medullary carcinoma in 1 breast and pleomorphic lobular carcinoma in the other. The phenotype of the primary tumors and corresponding metastatic tumors was similar for the expression of ER-alpha (p=0.001), PR (p=0.03), and HER-2 (p=0.018). While strong coexpression of HER-2 and ER-alpha is exceptional in hereditary breast carcinoma and sporadic breast carcinoma, 6/8 (75%) patients in this study had tumors with strong coexpression of HER-2 and ER-alpha. P53 protein expression was found in only 2/15 (13%) primary tumors, which is in contrast to BRCA1-related hereditary bilateral breast carcinomas, which often express p53 protein. Most of the patients presented with axillary metastases and had very aggressive course. Characteristically, the tumors showed high levels of expression of ER-alpha and Her2 amplification, were bcl-2 positive, and had high Ki-67 fraction. However, in patients with atypical medullary carcinoma there was no expression of ER-alpha or amplification of Her-2.
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PMID:Simultaneous bilateral breast carcinomas: a category with frequent coexpression of HER-2 and ER-alpha, high Ki-67 and bcl-2, and low p53. 1608 78

Occurrence of male breast cancer, a rare disease, peaks at age 71 years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Occupational risks include high temperature environments and exhaust fumes, but electromagnetic fields have not been implicated. Hyperoestrogenisation resulting from Klinefelter's, gonadal dysfunction, obesity, or excess alcohol, all increase risk as does exposure to radiation, whereas gynaecomastia does not. Presentation is usually a lump or nipple inversion, but is often late, with more than 40% of individuals having stage III or IV disease. Most tumours are ductal and 10% are ductal carcinoma in situ. Surgery is usually mastectomy with axillary clearance or sentinel node biopsy. Indications for radiotherapy, by stage, are similar to female breast cancer. Because 90% of tumours are oestrogen-receptor-positive, tamoxifen is standard adjuvant therapy, but some individuals could also benefit from chemotherapy. Hormonal therapy is the main treatment for metastatic disease, but chemotherapy can also provide palliation. National initiatives are increasingly needed to improve information and support for male breast cancer patients.
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PMID:Male breast cancer. 1648 3

Approximately half of lung cancer patients present with metastases, and a large proportion will develop recurrent disease, with median survival to cisplatin-based chemotherapy of 11 months. No predictive factor of response to cisplatin-based chemotherapy is yet available in clinical practice. The nucleotide excision repair system plays a major role in repairing a variety of distorting lesions, notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing cisplatin DNA damage. We carried out three different studies examining individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin-embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated advanced non-small-cell lung cancer (NSCLC) patients. Median survival was significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is involved in homologous recombination repair, and we observed that low levels of BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated patients. Our observations lead us to recommend that tumors be regularly assessed for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin treatment.
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PMID:Pharmacogenomics and gemcitabine. 1680 41

Molecular signaling events regulate cellular activity. Cancer stimulating signals trigger cellular responses that evade the regulatory control of cell development. To understand the mechanism of signaling regulation in cancer, it is necessary to identify the activated pathways in cancer. We have developed RepairPATH, a computational algorithm that explores the activated signaling pathways in cancer. The RepairPATH integrates RepairNET, an assembled protein interaction network associated with DNA damage response, with the gene expression profiles derived from the microarray data. Based on the observation that cofunctional proteins often exhibit correlated gene expression profiles, it identifies the activated signaling pathways in cancer by systematically searching the RepairNET for proteins with significantly correlated gene expression profiles. Analyzing the gene expression profiles of breast cancer, we found distinct similarities and differences in the activated signaling pathways between the samples from the patients who developed metastases and the samples from the patients who were disease free within 5 years. The cellular pathways associated with the various DNA repair mechanisms and the cell-cycle checkpoint controls are found to be activated in both sample groups. One of the most intriguing findings is that the pathways associated with different cellular processes are functionally coordinated through BRCA1 in the disease-free sample group, whereas such functional coordination is absent in the samples from patients who developed metastases. Our analysis revealed the potential cellular pathways that regulate the signaling events in breast cancer.
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PMID:Computational exploration of the activated pathways associated with DNA damage response in breast cancer. 1683 43


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