Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors analyzed the clinical and pathomorphological of T tumors for their association with the likelihood of axillary metastases. Two hundred forty three patients with early breast cancer (T1N0M0 T1N1M0) were studied. All underwent complete lymph node dissection. The parameters of the primary tumor evaluated included size, histologic subtype, hystological grade, hormone receptor status, lymphatic/vascular invasion (LVI). Clinical parameters were age, menopausal status and clinical lymph node status. Sixty two (25.5%) on 243 axillary dissection contained metastases. Univariate analysis showed that nodal involvement were associated with tumors larger than 1 cm and presence of LVI. Decision for complete axillary dissection should be individualized based on prognostic factors for lymph node involvement.
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PMID:[Prognostic factors and the risk of axillary metastases in early breast cancer]. 1036 51

In 1991, our group was the first to report the prognostic strength of plasminogen activator inhibitor type 1 (PAI-1) in primary breast cancer. The prognostic impact of invasion markers PAI-1 and urokinase-type plasminogen activator (uPA) on disease-free survival (DFS) and overall survival (OS) in breast cancer has since been independently confirmed. We now report on the prognostic impact of PAI-1 and uPA after long-term median follow-up of 77 months for our cohort (n = 316). Levels of uPA, PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. S-phase fraction (SPF) was measured flowcytometrically in paraffin sections. Using log-rank statistics, optimized cutoffs were found for PAI-1 (14 ng/mg), uPA (3 ng/mg), cathepsin D (41 pmol/mg), and SPF (6%). In all patients, various factors (PAI-1, uPA, nodal status, SPF, cathepsin D, grading, tumor size, hormone receptor status) showed significant univariate impact on DFS. In Cox analysis, only nodal status (p < 0.001, RR: 3.1) and PAI-1 (p < 0.001, RR: 2.7) remained significant. In node-negative patients (n = 147), PAI-1, uPA, and SPF had significant univariate impact on DFS, whereas in Cox analysis, only PAI-1 was significant. PAI-1 was also significant for DFS within subgroups defined by established factors. In CART analysis, uPA enhanced the prognostic value of PAT-1 and nodal status for determination of a very-low-risk subgroup. For OS, only lymph node status and PAI-1 were significant in multivariate analysis. PAI-1 levels in the primary tumor were also a significant prognostic marker for survival after first relapse in both univariate and multivariate analysis.
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PMID:Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following first relapse. 1042 5

Breast cancer rarely occurs in women below the age of 35 years. Data from various sources indicate that diagnosis at such an age is associated with a dire prognosis mainly because of a more aggressive presentation. Although the effect of chemotherapy for premenopausal patients is substantial, recent evidence on 2233 patients suggested that very young women with endocrine-responsive tumors had a statistically significantly higher risk of relapse than older premenopausal patients with such tumors. In contrast, results for younger and older premenopausal patients were similar if their tumors were classified as endocrine nonresponsive. Information from studies on 7631 patients who were treated with chemotherapy alone in trials of three major U.S. cooperative groups showed a similar interaction between the effect of age and steroid hormone receptor status of the primary tumor. Better treatments for very young patients are required and may involve ovarian function suppression in addition to other endocrine agents in patients with endocrine responsive tumors and a more precise investigation of chemotherapy and its timing, duration, and intensity in those with endocrine nonresponsive tumors. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues, which further complicate the phase of treatment decision making. The development of more effective therapies for younger patients requires tailored treatment investigations and cannot rely on information predominantly contributed from older premenopausal women.
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PMID:Adjuvant therapy for very young women with breast cancer: need for tailored treatments. 1177 91

We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.
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PMID:Stem cell dose and tumorbiologic parameters as prognostic markers for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous blood stem cell support. 1179 20

Breast cancer is a heterogenous disease with significant variations in biologic potential, ranging from small, low-grade, DCIS discovered mammographically with essentially no impact on patient survival to rapidly growing, palpable, locally advanced invasive breast cancer with clinically palpable nodal metastasis. The current challenge is to identify the clinical, pathologic, and molecular factors that determine the biologic potential of a particular breast cancer. Although size, nodal status, histologic grade, age, surgical margin, and hormone receptor status of breast cancer are the most important prognostic factors, the focus of research must be beyond these factors to other nonspecific prognostic information. Bone marrow micrometastasis may be an important factor to help predict outcome (7a) and the complement of sentinel node biopsy, bone marrow analysis, and primary tumor features may allow physicians to better select therapy. With increased understanding of the individual molecular events that control the invasive potential of a particular cancer, practitioners should be better able to predict more accurately which patients have little risk of recurrent disease or metastasis and would be best served by surgery alone versus patients who have a high risk of recurrent and metastatic disease and who should receive multimodality care.
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PMID:Contemporary management of breast cancer. 1189 65

The role of sex hormones in the pathogenesis of lung cancer is still unknown. There are conflicting results regarding immunohistochemical detection of the estrogen and progesterone receptors expression in non small cell lung cancer. To clarify these discrepancies 32 samples of lung carcinoma tissues obtained by lobectomy or pneumonectomy were studied. Two monoclonal antibodies (6F11 and ID5) for estrogen receptor detection and one (1A6) for progesterone receptor detection were used. Eighteen adenocarcinoma and 14 squamous cell carcinoma cases were investigated. There were 11 women and 7 men with adenocarcinoma and 4 women and 10 men with squamous cell carcinoma. Weak (+1) nuclear estrogen hormone receptor expression was detected in only one specimen of a woman with adenocarcinoma and in one specimen of a man with squamous cancer. None of the 32 blocks of paraffin embedded specimens expressed progesterone receptor. The positive estrogen and progesterone receptors expression in cancer tissue is an important argument against the pulmonary origin of the unknown primary tumor.
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PMID:Estrogen and progesterone receptors in non small cell lung cancer patients. 1202 90

The prognosis of cancer is primarily dependent on its potential to invade and metastasize. Data from both preclinical and clinical studies strongly suggest that serine proteases, as well as their inhibitors and receptor, play a central role in the processes leading to metastasis. We therefore investigated the prognostic value of plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2) and the combination of both inhibitors in 332 patients with operable breast cancer. PAI-1 and PAI-2 content was measured in the primary tumor cytosols using an enzyme-linked immunosorbent assay. For PAI-1 the median value (3.9 ng/mg protein) was used as cutoff, while the optimized cutoff for PAI-2 (6.5 ng/mg protein) was obtained using the log-rank statistic. After a median follow-up of 46 months 96 (29%) patients relapsed. In univariate analysis patients with a high PAI-1 or a low PAI-2 content had an increased risk of relapse. The difference was statistically significant for PAI-1 (p<0.0001) and almost statistically significant for PAI-2 (p=0.057). Stage, tumor size, differentiation grade, lymph node status and hormone receptor status also showed significant univariate impact on disease-free survival (DFS). In multivariate analysis (Cox model) PAI-1 (p<0.0001, RR=2.78), PAI-2 (p=0.0075, RR=2.17), UICC stage (p=0.0014, RR=2.2), differentiation grade (p=0.0097, RR=1.91) and nodal status (p<0.0001, RR=2.9) retained their significance. When both inhibitors were combined the worst prognosis was observed in patients with simultaneous high PAI-1 and low PAI-2 levels, whereas low PAI-1 in combination with high PAI-2 values indicated a very favorable prognosis. In conclusion, our study showed that both PAI-1 and PAI-2 had independent prognostic value in breast cancer. Combination of both inhibitors further improved the differentiation of patients with respect to prognosis.
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PMID:Prognostic value of plasminogen activator inhibitors in breast cancer. 1211 88

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.
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PMID:P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support. 1211 43

Treatments for men with breast cancer are based largely on accepted regimens for women with the disease. Surgical treatment of the primary tumor should be a mastectomy. Lymph node assessment can be done by conventional axillary node dissection or, similar to selected women with small primary tumors, by sentinel node dissection. Decisions regarding adjuvant systemic treatment should be made on the same basis as for women. Axillary node status, tumor size, hormone receptor status, and the health of the patient are important considerations in determining what adjuvant treatment is offered. The role of radiation after mastectomy in men is not well defined, but radiation should be used in patients at high risk for local recurrence. For patients with metastatic disease, treatment is based on the hormone receptor status of the tumor and is similar to the treatment for women. Because most men with breast cancer have hormone receptor-positive disease, hormonal therapy is a mainstay of treatment and tamoxifen remains the front-line drug of choice, although the latest generation of aromatase inhibitors have supplanted tamoxifen as a first-line therapy for women. As a second-line hormonal therapy for men, orchiectomy or a luteinizing hormone-releasing hormone agonist with or without an antiandrogen are reasonable alternatives. There are no reports regarding the use of the antiestrogen fulvestrant in men, but its mechanism of action and efficacy in women suggest that it will be a useful agent in hormone receptor-positive male breast cancer. For men with hormone-resistant disease, palliative chemotherapy with the same agents used for treatment of women with breast cancer is appropriate.
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PMID:Male breast cancer. 1259 42

To enable individualized risk-oriented adjuvant treatment of breast cancer, validated parameters are needed to help evaluate the individual relapse risk. The clinical significance of these factors is assessed by published evidence (level of evidence) and its utility in the clinical setting (utility score). The traditional prognostic factors (age, TNM stage, grading, and steroid hormone receptor status are of established clinical relevance, and their determination should be obligatory. Of the "new" tumor-biologic parameters, only the measurement of the urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in the primary tumor of node-negative patients has been adequately validated and can therefore be recommended for clinical application. Promising recent prognostic markers are the expression of Her2/neu, detection of disseminated tumor cells in bone marrow aspirates, various different surrogates for proliferative activity, and tumor-specific gene expression profiles. Currently, however, the data available are insufficient to allow recommendation of the parameters for routine clinical use at this time.
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PMID:[Prognostic factors in carcinoma of the breast. Thereupon depends success of the treatment]. 1286 97


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