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)

The aim of this study was to evaluate the role of retinoblastoma protein (pRb), alone and in combination with p16, as a predictive marker for metastases in non-sentinel nodes in cases where the sentinel node showed metastatic breast carcinoma. Paraffin blocks of lymph nodes from 48 patients with metastatic breast carcinoma were immunostained with a monoclonal antibody to retinoblastoma protein (PharMingen). Results were compared with known prognostic parameters of the primary tumor, estrogen and progesterone receptor status, proliferation index, and p16 (DAKO) expression. Lymph nodes from 38 of the 48 (79%) cases were pRb positive. There was no correlation of pRb staining alone with the primary tumor parameters studied or the proliferative index of the metastatic tumor. In 16 patients with both a sentinel node biopsy and an axillary lymph node dissection, 8 (50%) had metastatic breast carcinoma. The sentinel nodes of three of these eight patients (38%) were pRb negative (positive predictive value of 60% vs. 73% for p16). The remaining eight patients (50%) had no metastases in non-sentinel nodes, even though their sentinel nodes had metastatic breast carcinoma; six of these eight patients (75%) were pRb positive (negative predictive value of 55% vs. 83% for p16). pRb and p16 staining results combined showed that pRb-negative/p16-positive cases were associated with non-sentinel node metastases (positive predictive value of 100%) as well as poor prognostic parameters. Patients with the opposite staining profile (pRb positive and p16 negative) were mostly without non-sentinel node metastases (negative predictive value of 75%). Cases negative for both pRb and p16 were consistently associated with a better prognostic phenotype and absence of additional axillary node metastases. In conclusion, the presence or absence of pRb in sentinel nodes is of little predictive value for non-sentinel node metastases unless taken in conjunction with the presence of p16 staining. Instead, it appears to enhance the positive predictive value of p16 in determining the presence of non-sentinel node metastases. Due to the limited subgroup sample size in this study, clinical guidelines cannot be suggested as yet, but further research focused on the pRb-negative/p16-positivie and pRb-negative/p16-negative phenotypes may yield beneficial results.
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PMID:Expression of retinoblastoma protein in breast cancer metastases to sentinel nodes: evaluation of its role as a marker for the presence of metastases in non-sentinel axillary nodes, and comparison to p16INK4a. 1654 Jul 33

The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression.
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PMID:Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression. 1670 53

Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. However, due to lack of ER+ models, little is known about the role of hormones in breast cancer spread or the effects of the LN microenvironment on hormone responsiveness. We have developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors are tracked in living mice by whole-body imaging, and macrometastases or micrometastases are detected by intravital imaging or fluorescence microscopy. Tumor growth is estrogen dependent and required for intratumoral lymphangiogenesis. Seventy-five percent of all tumors and >95% of larger tumors generate LN metastases. Occasionally more distant metastases are also observed. "Triads" of primary tumors, tumor-filled draining lymphatic vessels, and tumor-filled LNs from the same mouse show that (a) proliferation, as measured by 5-bromo-2'-deoxyuridine uptake, is higher in the LN than in the primary tumor. (b) High ER levels are extensively down-regulated by estradiol in primary tumors. However, there is partial failure of ER down-regulation in LNs associated with (c) reduced PR expression. This suggests that ER are dysfunctional in the LN microenvironment and perhaps hormone resistant. (d) CD44 is sparsely expressed in primary tumor cells but homogeneously overexpressed in cells transiting the lymphatics and populating LNs. We hypothesize that CD44 expression targets tumor cells for transport to, and uptake in, LNs. If so, the CD44 pathway could be targeted therapeutically to slow or prevent LN metastases.
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PMID:Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity and tumor aggressiveness in lymphatic vessels and lymph nodes. 1698 76

Reactive oxygen species (ROS), including nitric oxide (NO(*)), are associated with all steps of carcinogenesis. Hyaluronan (HA), a high-molecular-mass glycosaminoglycan overexpressed in a variety of human malignancies also has ROS-scavenging properties. We histochemically studied the level of HA in breast carcinoma cells and their stroma and compared it with the expression of NO(*) synthases (NOSs), major antioxidant enzymes, and nitrotyrosine. We also assessed whether the level of HA correlates with traditional prognostic factors of breast cancer and survival. Stromal HA level was moderate or high in all the samples studied (n=185), and 84% of the lesions showed HA-positive carcinoma cells. Intense stromal HA signal was associated with high neuronal NOS expression (p=0.009), whereas tumor-cell associated HA was inversely correlated with nitrotyrosine expression (p=0.027). Of the traditional prognostic factors, tumor cell-associated HA was correlated with poor differentiation (p=0.011), and high stromal HA levels were associated with aggressive features of the carcinomas such as large primary tumor (p=0.002), poor differentiation (p=0.019), and estrogen (p=0.012) and progesterone receptor negativity (p=0.009). High stromal HA level also significantly predicted poorer survival. The strong positive correlation between neuronal NOS and stromal HA could reflect NO(*)-stimulated synthesis of HA, an extracellular matrix alteration that favors breast cancer progression. Furthermore, it is suggested that, while acting as a scavenger of NO(*)-derived radicals, cell-associated HA undergoes partial fragmentation, release from receptors, and further degradation in lysosomes, and thus becomes undetectable in histological sections.
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PMID:Hyaluronan in breast cancer: correlations with nitric oxide synthases and tyrosine nitrosylation. 1782 65

Women with early breast cancer are exposed to an ongoing risk of relapse, even after successful surgical resection of the primary tumor and, where given, radiotherapy. Adjuvant chemotherapy and/or endocrine therapy can further help to prevent relapses by targeting metastatic disease deposits, which may be present but clinically undetectable. The benefits of adjuvant therapy are well documented, and millions of relapses have undoubtedly been prevented by treatment in this setting. Adjuvant tamoxifen has proven particularly effective in preventing relapses in hormone-receptor-positive (HR+) disease, and has been the standard treatment for affected women for over 30 years. However, long-term exposure to tamoxifen is associated with an unfavorable risk: benefit profile due to decreasing efficacy and an increasing incidence of harmful side effects. Although the risk of relapse is highest during the first 2-3 years after surgery, a residual risk remains indefinitely for those women who do not experience disease relapse in these early years, and the majority of all breast cancer recurrences and deaths occur after completion of 5 years of adjuvant tamoxifen. Hence, there is a great need for additional adjuvant therapies to reduce the considerable risk of late relapses in patients with HR+ disease: until recently no agent had been shown to provide a significant benefit over no further treatment. In 2003, upon publication of the first interim analysis of the MA.17 trial, letrozole became the first agent to be shown to significantly reduce relapses in women with HR+ early breast cancer who had completed 5 years of adjuvant tamoxifen. Subsequent analyses confirmed that letrozole significantly reduced recurrences, including distant metastases, and, in patients with node-positive disease, the agent also significantly improved overall survival, with the benefit of letrozole increasing with duration of therapy, at least up to 48 months. Preliminary results from a small, open-label study suggest that extended anastrozole therapy can also improve outcomes after completion of standard adjuvant tamoxifen. Ongoing analyses from MA.17, investigating how estrogen and progesterone receptor status and the length of time since finishing tamoxifen influence the effectiveness of letrozole, and studies evaluating the safety and efficacy of 10 years of extended aromatase inhibitor therapy, will help to optimize extended adjuvant therapy and improve outcomes for women with HR+ early breast cancer.
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PMID:Reducing the risk of late recurrence in hormone-responsive breast cancer. 1789 Feb 10

Metastasis of cancer cells from the primary tumor is associated with poor prognosis and decreased overall survival. One protein implicated in inhibiting metastasis is the tumor metastasis suppressor nonmetastatic protein 23 homologue 1 (NM23-H1). NM23-H1 is a multifunctional protein, which, in addition to limiting metastasis, has DNase and histidine protein kinase activities. We have identified new functions for NM23-H1 in influencing estrogen receptor alpha (ER alpha)-mediated gene expression. Using a battery of molecular and biochemical techniques, we show that NM23-H1 interacts with ER alpha and increases the ER alpha-estrogen response element (ERE) interaction. When NM23-H1 expression is increased in U2 osteosarcoma and MDA-MB-231 breast cancer cells, transcription of a transiently transfected, estrogen-responsive reporter plasmid is decreased. More importantly, when endogenous NM23-H1 expression is knocked down in MCF-7 human breast cancer cells using small interfering RNA, estrogen responsiveness of the progesterone receptor (PR), Bcl-2, cathepsin D, and cyclin D1 genes, but not the pS2 gene, is enhanced. Furthermore, NM23-H1 associates with the region of the PR gene containing the +90 activator protein 1 site, but not with the ERE-containing region of the pS2 gene, indicating that NM23-H1 mediates gene-specific effects by association with endogenous chromatin. Our studies suggest that the capacity of NM23-H1 to limit the expression of estrogen-responsive genes such as cathepsin D and Bcl-2, which are involved in cell migration, apoptosis, and angiogenesis, may help to explain the metastasis-suppressive effects of this protein. The complementary abilities of ER alpha and NM23-H1 together to influence gene expression, cell migration, and apoptosis could be key factors in helping to determine tumor cell fate.
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PMID:Interaction of the tumor metastasis suppressor nonmetastatic protein 23 homologue H1 and estrogen receptor alpha alters estrogen-responsive gene expression. 1797 5

The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers.
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PMID:ID genes mediate tumor reinitiation during breast cancer lung metastasis. 1804 29

Lymph node (LN) status is the most important factor in predicting survival in breast cancer. Historically, patients with 10 or more positive LN have been thought to have a particularly poor prognosis, which has in the past been used to alter therapeutic recommendations. Studies conducted both prior to and after the use of anthracycline-based chemotherapy demonstrate poor survival. We hypothesized that the current survival rate is considerably higher. All patients with breast cancer treated at our institution between July 1991 and December 2005 with at least 10 positive axillary LN were identified. A multivariate Cox proportional hazards model was performed using age, number of positive nodes, and primary tumor characteristics. Of 55 patients identified, two were excluded for incomplete follow-up information. The median patient age was 53; median follow-up was 5-years. The overall 5-year survival rate was 71.9%. On univariate analysis estrogen receptor (ER) status (p = 0.0001), progesterone receptor status (p = 0.004), use of adjuvant chemotherapy (p = 0.01), T-stage (p = 0.03), and adjuvant hormonal therapy (p = 0.002) were statistically significant for survival. In the multivariate analysis, only ER status and the use of adjuvant chemotherapy remained significant for survival. ER negativity conferred a hazard ratio of 12.6 (95% confidence interval: 3.7-43.2) and the use of adjuvant chemotherapy had a hazard ratio of 0.14 (95% confidence interval: 0.04-0.46). In our study, patients with at least 10 positive axillary LN had a 5-year survival of 71.9% which may be due to the improvements in local and systemic therapy.
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PMID:An update on prognosis in breast cancer patients with extensive axillary disease. 1808 70

Spontaneous mammary gland carcinomas occurred in five baboons during a 13-year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co-existent ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.
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PMID:Characterization of spontaneous mammary gland carcinomas in female baboons. 1819 73

By the year 2030 most patients with breast cancer will be aged 65 years or more and many will be frail. Frailty implies diminished physiologic reserve; contributors include diminished organ function, comorbidities, impaired physical function, and geriatric syndromes. Time-efficient tools for assessing frailty are being developed and, once validated, can be used to identify frail cancer patients and help direct therapy. Screening mammography in frail patients is questionable, and a clinical breast exam is likely to identify breast cancers that warrant intervention. Hormonal therapy may be a reasonable primary therapy in older frail women with hormone receptor-positive lesions. For estrogen receptor--and progesterone receptor-negative lesions, excision of the primary tumor may be adequate. Adjuvant hormonal therapy may be appropriate in frail elders with high-risk hormone receptor-positive breast cancer; chemotherapy is rarely indicated regardless of tumor status. The majority of frail elders with metastases will have hormone receptor-positive breast cancers, and endocrine therapy should be considered; those with receptor-negative tumors may be treated with single-agent chemotherapy or supportive care measures. Oncologists need to acquire the skills to appropriately identify frail elders so they select appropriate therapies that will minimize toxicity and maintain quality of life.
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PMID:Management of the frail elderly with breast cancer. 1824 18

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