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

We analyzed the age at diagnosis and the tumor size as determinants of axillary node involvement in 725 consecutive patients with breast cancer. The prevalence of nodal involvement increased consistently with tumor diameter from 18.9% in tumors smaller than 10 mm to 72.9% in those measuring 40 mm, or more. The risk also varied with age, the lowest prevalence being found in the youngest and the oldest patients and the highest one in the 40-59-year age group. When analyzed as a continuous variable age was best fitted as a second order term and it was a statistically significant (p = 0.04) determinant of axillary metastases in a multivariate model where tumor diameter, histopathological classification and estrogen receptor concentration were taken into account as possible confounding variables. The findings indicate that the parallelism between the establishment of metastases in lymph nodes and at distant sites may vary with age. The prognostic value of nodal status may therefore depend on age at diagnosis.
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PMID:Age as a determinant of axillary node involvement in invasive breast cancer. 141 99

Breast cancers containing estrogen receptors are responsive to antiestrogen treatment and have a better prognosis than estrogen receptor-negative tumors. The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated tumors. We transfected the human estrogen receptor into the estrogen receptor-negative metastatic breast cancer cell line MDA-MB-231 in an attempt to restore their sensitivity to antiestrogens. Two stable sublines of MDA-MB-231 cells (HC1 and HE5) expressing functional estrogen receptors were studied for their ability to grow and invade in vitro and to metastasize in athymic nude mice. The number and size of lung metastases developed by these two sublines in ovariectomized nude mice was not markedly altered by tamoxifen but was inhibited 3-fold by estradiol. Estradiol also significantly inhibited in vitro cell proliferation of these sublines and their invasiveness in Matrigel, a reconstituted basement membrane, whereas the antiestrogens 4-hydroxytamoxifen and ICI 164,384 reversed these effects. These results show that estradiol inhibits the metastatic ability of estrogen receptor-negative breast cancer cells following transfection with the estrogen receptor, whereas estrogen receptor-positive breast cancers are stimulated by estrogen, indicating that factors other than the estrogen receptor are involved in progression toward hormone independence. Reactivation or transfer of the estrogen receptor gene can therefore be considered as therapeutic approaches to hormone-independent cancers.
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PMID:Activation of estrogen receptor transfected into a receptor-negative breast cancer cell line decreases the metastatic and invasive potential of the cells. 145 45

The biological activities of steroid hormones are effected via intracellular receptors. The receptors are part of a ligand-activated family of transcription regulator proteins that are critical for steroid-regulated cell differentiation. With recombinant cDNA technology, yeast and cultured animal cells can be made to express mammalian cDNA steroid receptors from cDNA clones that contain deletions and substitutions. Among the leading problems addressed in these models is the characterization of sequences that promote association or interaction with other transcription regulating molecules, including oncogene products. Recently it has been found that heat shock proteins may serve not only to stabilize the receptor proteins but also to precondition the activation imparted by ligand binding. Aberrant receptor proteins can be found in ovarian cancer. Whether aberrant receptor proteins are associated with transformation in general or with a variable clinical response to steroidal or anti-steroidal therapy is not known. Even after chemotherapy, steroid receptors are expressed in the metastases of ovarian cancers seen clinically, and they may have potential uses for localization and treatment of receptor-rich cancers. Radioligand pharmaceuticals appropriate for imaging or for site-directed radiocytotoxicity can be sequestered to the nuclei of receptor-rich cancers. Initial clinical imaging and therapy trials with such pharmaceuticals have been approved and begun. In the use of halogenated estrogen radiopharmaceuticals, liver metabolism and enterohepatic recirculation are important considerations. Ascites prolongs retention of a radiohalogenated estrogen in the abdominal cavity. Distant metastases have been localized with [123I]-estrogen in breast cancer patients in pre-operative procedures. Receptor-mediated cytotoxicity occurs when estrogen receptor radioligand pharmaceuticals that are Auger electron emitters are used in vitro.
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PMID:Intracellular actions of steroid hormones and their therapeutic value, including the potential of radiohalosteroids against ovarian cancer. 150 90

Steroid hormone receptors have been evaluated as independent prognostic factors as well as predictive factors for endocrine manipulation in the clinical management of breast cancer. The contribution of each receptor or combinations of different receptors remains controversial. In cytosols from 224 patients with operable breast cancer (stages I & II), estrogen receptor (ER), progesterone receptor (PgR) and androgen receptor (AR) content have been measured. An improved AR-assay has been used in order to circumvent some of the problems inherent in other methods. In this study, 91.1% of the patients were classified as AR 'positive' (i.e. greater than or equal to 10 pmol/g). The steroid hormone receptors were significantly correlated (P less than 0.001). Taking the median value of AR as cut-off (50.5 pmol/g), a significantly higher incidence (P = 0.004) of node negative patients was found in the group with a lower AR content. In a multivariate analysis the AR category (median value used as cut-off) was shown to be an independent predictor of the likelihood of axillary metastases (P = 0.001). AR category, however, did not reveal any significant prognostic information concerning relapse free survival. A subpopulation of node positive patients with ER positive tumors, have been included in a randomized trial on the role of tamoxifen as an adjuvant treatment compared with no endocrine treatment. In a multivariate analysis, PgR status was shown to be a single independent prognostic factor (P = 0.016) for relapse free survival in patients with a lower AR content (less than median value). The improved AR assay used in the present study may provide a basis for more correct estimation of the AR content in an individual tumor. The present study suggests that AR analysis and the use of a well-chosen cut-off level may add information about tumor biology to increase our understanding of breast cancer biology and treatment.
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PMID:Androgen receptors in operable breast cancer: relation to other steroid hormone receptors, correlations to prognostic factors and predictive value for effect of adjuvant tamoxifen treatment. 158 3

Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy versus observation in high-risk node-negative breast cancer patients. 162 37

pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p = 0.001 and p = 0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known.
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PMID:pS2 expression in primary breast carcinomas: relationship to clinical and histological features and survival. 162 14

17 alpha-[123I]Iodovinyl-11 beta-methoxyestradiol was injected into 19 women: group 1 (n = 8), initial evaluation of breast cancer; group 2, (n = 11) postoperative follow-up including 9 patients with bone metastases. The primary tumor (size: 8-10 mm) was visualized by breast tomoscintigraphy in 2/4 patients of group 1 with high estrogen receptor concentration (162-445 fmol/mg) and was not detectable in 4 patients with low estrogen receptor concentration (6-32 fmol/mg). Axillary lymph node metastases were detected in 1 patient of group 1 and in 1 patient of group 2. In 4 patients of group 2 with previous primary tumor containing estrogen receptors, MIVE2 uptake in bone metastases was demonstrated. MIVE2 scintigraphy is an original, specific and non-invasive method for breast cancer estrogen receptor imaging in primary and in metastatic tumors.
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PMID:Estrogen receptor imaging with 17 alpha-[123I]iodovinyl-11 beta-methoxyestradiol (MIVE2)--Part II. Preliminary results in patients with breast carcinoma. 162 15

Resection of isolated pulmonary metastases may yield improved survival in select patients. Between 1981 and 1991, 44 women (median age, 55 years) with a history of breast cancer underwent 47 thoracotomies with no operative deaths and only three minor postoperative complications (3/47, 6.4%). Confirmation of the metastatic origin of the lung lesion was made by direct histological comparison with the primary. Three patients had benign nodules and were excluded, and 4 patients had less than complete resection at thoracotomy. The median survival after thoracotomy of the remaining 37 patients with completely resected metastases was 47 +/- 5.5 months, and their actuarial 5-year survival was 49.5%. Patients with a disease-free interval of longer than 12 months had a longer survival (median survival, 82 +/- 6 months; 5-year survival, 57%) than patients with a disease-free interval of 12 months or less (median survival, 15 +/- 3.6 months; 5-year survival, 0%) (p = 0.004). Patients with estrogen receptor-positive status (n = 14) tended to have longer survival after resection than patients with estrogen receptor-negative status (n = 15) (median survival, 81 +/- 9 months versus 23 +/- 6 months, respectively; p = 0.098). Other clinical variables analyzed did not predict survival after thoracotomy. We conclude that resection of pulmonary metastases in patients with breast cancer can be done safely and may result in long-term survival for a substantial number of patients. Patients with a disease-free interval of longer than 12 months have an excellent prognosis after complete resection.
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PMID:Long-term survival after resection of pulmonary metastases from carcinoma of the breast. 163 12

Prior studies have shown that overexpression of HER-2/neu occurs in one third of breast and ovarian cancers and that overexpression is associated with poor prognosis. We used a monoclonal antibody to assess immunohistochemically the level of HER-2/neu expression in normal and malignant endometrium. In 24 normal endometrial samples light to moderate (1+ to 2+) staining for HER-2/neu was seen in the glands, and there was no variation in intensity of staining during the menstrual cycle. Among 95 endometrial adenocarcinomas, nine (9%) were found to have heavier staining for HER-2/neu than was seen in normal endometrium (3+). High expression of HER-2/neu was found in 27% of patients with metastatic disease compared with 4% of patients with disease confined to the uterus (p less than 0.005). High HER-2/neu expression also was associated with absence of estrogen receptor (p less than 0.005) and with increased mortality from cancer. Further studies are needed to determine the significance of HER-2/neu overexpression in endometrial cancer.
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PMID:Overexpression of HER-2/neu in endometrial cancer is associated with advanced stage disease. 167 Sep 8

Data regarding the prognostic value of HER-2/neu protein expression in breast cancer are conflicting, perhaps because of short follow-up and technical difficulties in the determination (the admixture of benign elements with the biochemical method and the subjectivity of the immunohistochemical assessment). Therefore, using digital image processing, we compared the correlation between and the prognostic value of (a) quantitative immunohistochemical HER-2/neu protein expression and (b) clinical, morphometric, and flow-cytometric DNA ploidy features; histologic grade; and biochemically assessed estrogen receptor content. Paraffin-embedded invasive breast Pancers of 82 patients with long-term follow-up were used. None of the patients had received adjuvant systemic therapy. HER-2/neu protein expression was significantly correlated with DNA index, lymph node status, and tumor size and, in the diploid tumors, was weakly correlated with the percentage of S-phase cells. Strong HER-2/neu protein expression was associated with a worse prognosis (although not significantly, p = 0.07). No differences were detected between cancers with or without axillary lymph node metastases. In survival analysis, the Multivariate Prognostic Index and the morphometric features were much stronger prognosticators than HER-2/neu protein overexpression, which, however, had additional prognostic value to that of many of the features analyzed, especially when more than 35% HER-2/neu protein levels (relative to the high expression SKBR3 cell line) were present. Combined diploidy and HER-2/neu protein content greater than 35% occurred in a small group of patients (n = 3), all of whom died. Likewise, in tetraploid cancers a combination of S-phase cells greater than or equal to 7% and HER-2/neu protein content greater than 35% was an ominous sign. In multivariate analysis, strong HER-2/neu protein overexpression was prognostically over-shadowed by the morphometric features. Nevertheless, it is important to further analyze the intriguing possibility of identifying a subgroup of breast cancer patients with a very poor outcome merely using cytometric analysis of paraffin-embedded material of the primary tumor.
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PMID:Comparative long-term prognostic value of quantitative HER-2/neu protein expression, DNA ploidy, and morphometric and clinical features in paraffin-embedded invasive breast cancer. 167 89


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