UMLS:C0677930 - FACTA Search

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Query: UMLS:C0677930 (primary tumor)
20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conservatively treated premenopausal breast cancer has a higher rate of local relapse as well as an increased genetic predisposition to cancer. The current study's purpose was to evaluate the interactions between BRCA-1/2 status and molecular biologic markers in a cohort of conservatively managed breast cancer patients. Seventy-six premenopausal women treated with breast-conserving surgery and radiation therapy were this study's focus. All patients were treated with wide local excision with or without axillary dissection, followed by radiation to the intact breast. Systemic therapy was administered as clinically indicated. All patients in this study had an available paraffin block from the primary tumor and agreed to undergo complete sequencing of the BRCA-1 and BRCA-2 genes. The primary breast tumor tissue from each patient was immunohistochemically stained for estrogen receptor (ER), progesterone receptor (PR), p53, HER-2/neu, and Proliferating Cell Nuclear Antigen (PCNA). Of the 76 patients tested for BRCA, 50 patients had wild-type BRCA-1 and BRCA-2, 15 had variants of unclear significance, 6 had deleterious mutations in BRCA-1, and 5 had deleterious mutations in BRCA-2. p53 positivity correlated with deleterious mutations in BRCA-1 (p = 0.023), but not in BRCA-2. Though not significant, there was a trend for ER and PR negativity to correlate with BRCA-1 mutation (p = 0.087 and 0.054, respectively); there were no correlations between ER, PR, and BRCA-2. Though not significant, all 11 tumors with BRCA mutations were HER-2/neu negative. Patients with BRCA mutations have a unique molecular profile. These data can be helpful in understanding differences in the biologic behavior of patients with familial breast cancers.
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PMID:BRCA status, molecular markers, and clinical variables in early, conservatively managed breast cancer. 1275 24

Chromosomal copy number aberrations (CNAs) are common in breast cancer and involve genomic regions in a frequency and combination, suggesting distinct routes of tumor development. We studied chromosomal gains (+) and losses (-) by comparative genomic hybridization from a series of 305 unselected primary invasive breast cancers. CNAs were observed in >90% of the tumors and involved all chromosomal arms in various frequencies, the most common being +1q (55%), +8q (41%), +16p (40%), +17q (28%), -13q (27%), -16q (22%), +20q (19%), -8p (18%), and +11q (16%). Eighteen pairs of CNAs were revealed as significantly associated using Fisher's exact test with Bonferroni correction, the most common pairs being -8p/+8q, +17q/+20q, and -4q/-13q. To study more complex relationships between individual CNAs, principal component analysis and distance-based tree modeling were performed independently. Three distinct patterns of CNAs were observed. Group A was defined by +1q, +16p, and -16q, group B by +11q, +20q, +17q, and -13q, and group C by -8p and +8q. Group A was correlated to positive estrogen receptor and progesterone receptor (PgR) status (P < 0.001 and P < 0.05, respectively). Groups B and C were correlated to DNA nondiploidy (P < 0.001 and P < 0.05), high histological grade and lymph node positivity (P < 0.05), and group B also to high proliferation rate, large primary tumor size (P < 0.001), and negative PgR status (P < 0.05). Patients with aberrations in group A only had a significantly higher breast cancer survival rate than all other patients. The worst survival was seen for patients with aberrations in group C only along with the patients displaying aberrations from all CNA pattern groups (ABC). The 5-year survival rates vary from 96% in group A to 56% in group C. These correlations were independent of node status, tumor size, and PgR status in a multivariate analysis. We conclude that patterns of copy number gains and losses define breast tumors with distinct clinicopathological features and patient prognosis.
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PMID:Patterns of chromosomal imbalances defines subgroups of breast cancer with distinct clinical features and prognosis. A study of 305 tumors by comparative genomic hybridization. 1469 3

Increased detection rate in the lymph nodes is seen with serial sectioning or immunohistochemistry (IHC), but the importance of occult metastases is not resolved. IHC is still not recommended in routine examination of lymph nodes. Axillary lymph nodes from 385 node-negative breast cancer patients with a median follow-up of 25 years were examined with IHC for cytokeratins, applied on routine sections. The association between classic histopathologic prognostic factors and the presence of occult metastases was evaluated. Metastases were found in 45 of 385 cases (12%), 21 metastases (47%) measured < or =0.2 mm, 8 (18%) were larger than 2 mm; 14 metastases were located in the subcapsular sinus, 22 in the parenchyma of the lymph node; and 51% (23/45) of the metastases were recognized on hematoxylin-eosin staining on "second look." The detection of metastases was significantly associated with the number of sectioned lymph nodes (6% metastases for one to five lymph nodes examined versus 17% for more than five lymph nodes) and with histologic subtype (metastases in 11% of the ductal versus 33% of the lobular carcinomas). No significant association was found between occult metastases and age, tumor size, histologic grade, estrogen or progesterone receptor status, p53, or c-erbB-2. Metastases larger than 2 mm predicted a poorer recurrence-free survival rate for the whole series. A subcapsular location of the metastases was a strong predictor of overall survival. Whether or not the metastases could be identified on hematoxylin-eosin sections did not have any prognostic significance. In the multivariate analysis, histologic grade, tumor size of the primary tumor, progesterone receptor status, and the presence of occult metastasis in the lymph nodes had a prognostic impact on survival with a 25-year follow-up.
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PMID:Occult metastases in axillary lymph nodes as a predictor of survival in node-negative breast carcinoma with long-term follow-up. 1512 40

A mammary tumor cell line, designated MTCL, was successfully established from a mouse primary mammary tumor (MTP). The MTCL cells retain cytokeratin and both estrogen receptor (ER) and progesterone receptor (PR) in vitro. In vitro exposure of MTCL cells to progesterone causes a decrease in the cellular (3)H-thymidine uptake, indicating an inhibition by progesterone on MTCL cellular deoxyribonucleic acid synthesis, whereas exposure of the cells to a high dose of estrogen (15 pg/ml) for 48 h causes an increase of (3)H-thymidine uptake. We inoculated both MTP or MTCL tumor cells into normal cycling female C(3)HeB/FeJ mice and demonstrated that the post-resection metastatic recurrence of MTCL tumors, like the original MTP tumors, depends on the time of tumor resection within the mouse estrous-cycle stage. Both MTCL and MTP tumors have similar histological appearances with the exception of less extensive tumor necrosis and higher vascularity in MTCL tumors. Equivalent levels of sex hormone receptors (ER alpha, ER beta, and PR), epithelial growth hormone receptors (Her2/neu, EGFR1), tumor suppressors (BRCA1, P53), and cell apoptosis-relevant protein (bcl-xl) were found in these in vivo tumors by immunohistochemistry. Cyclin E protein, however, was significantly higher in MTP tumors compared with MTCL tumors. Our results indicate that MTCL cells retain many of the biologic features of the original MTP primary tumor cells, and to our knowledge, it is the first in vitro cell line that has been shown to maintain the estrous-cycle dependence of in vivo cancer metastasis.
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PMID:Creation of a stable mammary tumor cell line that maintains fertility-cycle tumor biology of the parent tumor. 1516 41

Disseminated tumor cells (DTC) in bone marrow are independently related to poor outcome in patients with breast cancer. Phenotypic characterization of DTC may be useful to improve evaluation of the metastasizing potential of DTC and also to more accurately target aggressive tumor cells. DTC were screened in bone marrow aspirates from breast cancer patients by immunocytochemistry with an anticytokeratin (anti-CK) antibody (A45B/B3). Because the cell permeabilization and fixation required for intracellular CK staining is deleterious for mRNA, we used microaspiration to isolate single tumor cells stained with a monoclonal antibody directed against a membrane epitope, epithelial cell adhesion molecule (EpCAM), in CK-positive cases. Urokinase-type plasminogen activator receptor (uPAR) was quantified by real-time quantitative RT-PCR. The SKBR3 human breast cancer cell line was used to calibrate RT-PCR. A linear relationship was observed between the cycle threshold (Ct) of uPAR and 18S gene expression and SKBR3 cells spiked (1, 3, 7, 10 and 20) in control patient bone marrow. EpCAM-positive cells were aspirated in 21 out of 25 bone marrow specimens from breast cancer patients with CK-positive cells and uPAR mRNA expression was determined in 16 cases. A high level of uPAR mRNA in DTC was detected in 8 out of 16 patients (50%) and was associated with a more aggressive primary tumor phenotype (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative or HER2-positive) (p = 0.01). We demonstrated that real-time quantitative RT-PCR was reliably adapted to phenotype analysis of isolated micrometastatic cells. A larger study would be useful to confirm the importance of uPAR to define higher risk subgroups of breast cancer patients with micrometastatic disease.
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PMID:Real-time quantitative PCR determination of urokinase-type plasminogen activator receptor (uPAR) expression of isolated micrometastatic cells from bone marrow of breast cancer patients. 1554 15

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.
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PMID:[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases]. 1562 61

Malignant melanoma (MM), the most common metastatic solid tumor to involve the breast, may present as a diagnostic problem, frequently requiring the use of ancillary studies for accurate diagnosis. The implication of hormonal interplay is strong since metastatic MM to the breast is seen nearly always in women. However, the role of hormonal status as a predisposing factor in the development of this entity is largely unresolved. A number of chromosomal loci, including 1p36 and 9p21-22, appear to harbor critical genes important to melanoma tumorigenesis, and additionally chromosome 9q22.3-31. We wanted to know if metastatic MM in breast showed chromosome 1p and 9p genetic alterations (loss of heterozygosity) similar to those that occur in primary cutaneous MM, and whether additional 9q LOH changes are present. Hormonal receptor status of the metastatic MM was also determined. We identified 20 patients with known MM metastatic to the breast, which we analyzed with the following genetic markers: D9S12 (9q22.3), D9S171 (9p21), IFNA (9p22), and D1S450 (1p). Visually directed microdissection was performed on archival histologic slides containing both tumor and adjacent normal breast epithelium, followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification for evaluation of loss of heterozygosity (LOH) for the above-listed markers. Immunohistochemical (IHC) stains for estrogen receptor (ER) and progesterone receptor (PR) was performed on 10 of the cases. Twelve of the 20 cases contained DNA suitable for PCR amplification following direct visualization microdissection. Four of 8 (50%) informative cases showed LOH at 9p21 with D9S171. Ten cases were heterozygous for IFNA, with 2 cases (20%) showing LOH at this locus. These particular cases also showed LOH at 9p21. One of 9 (11%) informative cases showed LOH for D1S450 (1p36). Five cases were heterozygous for D9S12, and 2 (40%) showed LOH in the tumor at 9q22.3. IHC stains for ER and PR were negative in the 10 tumors studied. Metastatic MM presenting as a breast mass is an interesting entity often requiring IHC studies for diagnosis, particularly when the histologic features simulate breast carcinoma or when no primary tumor is known. These tumors are ER and PR negative. Metastatic MM involving the breast shows similar genetic allelic losses on chromosome 9p21-22 (50%) and 1p36 (11%), as previously described in primary cutaneous MM. Additional LOH was observed at the 9q22.3-31 locus (40%). We suggest this locus to be investigated for harboring potential genes important in the tumorigenesis of cutaneous MM.
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PMID:Loss of heterozygosity on chromosome 1 and 9 and hormone receptor analysis of metastatic malignant melanoma presenting in breast. 1573 50

Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with locally advanced breast cancer (LABC). This was a retrospective review of 21 consecutive women who received NACT as initial treatment of LABC, followed by surgical excision. The pre- and post-treatment breast specimens and post-treatment axillary lymph nodes with metastases were immunostained to evaluate for proliferative index (PI) (MIB-1 Immunotech) and vascular endothelial growth factor (VEGF) expression (Santa Cruz, CA, clone A-20). Thirteen of the 21 patients (62%) had more than 50% tumor shrinkage following NACT. The breast's mean PI decreased from 47.86% to 23.95% after treatment (P = 0.005). The mean PI in the post-treatment lymph nodes was 24.47%. A nodal post-NACT PI of less than 10% and progesterone receptor-positive tumor status were associated with better survival, as all such patients are alive. A high PI after NACT was associated with recurrence or death. All of the patients who showed an excellent clinical response had either a decrease in the PI or an absence of a high level of VEGF after NACT. Most patients exhibited persistent expression of VEGF after NACT. Pathologic response in the primary tumor did not correlate with the response in the lymph nodes or with overall survival. NACT reduces the size and PI of the primary breast tumor independent of the patient's node status. The PI may be an early means by which to identify tumors most likely to reduce in size with chemotherapy. A low PI after NACT is associated with better survival. There is persistent expression of VEGF in post-NACT residual breast carcinoma. Thus, anti-VEGF drugs after conventional chemotherapy may benefit patients with residual carcinoma.
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PMID:Expression of vascular endothelial growth factor and proliferation marker MIB1 are influenced by neoadjuvant chemotherapy in locally advanced breast cancer. 1589 27

The clinical courses of patients with recurrent breast carcinoma vary greatly. We retrospectively examined data on 1863 Japanese patients treated for a breast carcinoma from 1981 to 2000. Among them, 345 (18.5%) who had clearly died of recurrence were reviewed. Patients died most frequently (63.2%) up to 30 months after the first recurrence. Based on multivariate analysis, the four factors that were most predictive of survival after the first recurrence were disease-free interval, site of recurrence, progesterone receptor (PgR) status, and vascular involvement. These findings showed that the intrinsic tumor biology of the initial primary tumor plays a critical role in determining survival after the first recurrence in patients with a breast carcinoma. The combined analysis of disease-free interval, site of recurrence, PgR status, and vascular involvement may assist in estimating the median survival after first recurrence, and may assist with the designing of new therapeutic strategies for patients with recurrence for whom there is an unfavorable prognosis.
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PMID:Prediction of survival from first recurrence of breast carcinoma in Japanese women. 1600 34

Several studies have demonstrated that tumor cell-derived RNA is presented in the plasma from breast cancer patients. However, no studies have focused on the detection of plasma erbB2 mRNA in breast cancer. In this study the expression of erbB2 mRNA in the plasma was analyzed in 106 breast cancer patients and 50 healthy subjects by using a nested RT-PCR strategy, and the circulating tumor cells were also detected by using a nested RT-PCR for detection of mammaglobin transcripts in the peripheral blood. Plasma erbB2 mRNA was detectable in 46 (43.3%) breast cancer patients, whereas only 5 normal subjects (10%) were positive in the control group (p = 0.001). The presence of erbB2 mRNA in the plasma was not associated with menopausal status, erbB2 expression in primary tumor tissues, tumor size, histological grade, Ki-67 expression or lymph node involvement, but it exhibited a trend for correlation with increasing tumor stages (p = 0.085), and the presence of erbB2 mRNA in the plasma was significantly associated with negative estrogen receptor (ER) and progesterone receptor (PR) status of the primary tumors (p = 0.031 and 0.026, respectively). Furthermore, in a small subset of 36 breast cancer patients we found the presence of plasma erbB2 mRNA was significantly correlated with the occurrence of circulating tumor cells (p = 0.01). Our study suggests that breast cancer patients with the presence of erbB2 mRNA in the plasma may have a high malignancy or an aggressive phenotype, and frequently detecting plasma erbB2 mRNA may provide a novel approach for monitoring breast cancer progression or response to treatment.
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PMID:Presence of erbB2 mRNA in the plasma of breast cancer patients is associated with circulating tumor cells and negative estrogen and progesterone receptor status. 1631 78

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