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 CHEK2 kinase is a tumor suppressor whose activation in response to DNA double-strand breaks contributes to cell cycle arrest or apoptosis. The c.1100delC mutation is associated with familial breast cancer, and tumors from mutation carriers show reduced or absent CHEK2 protein expression. We have here studied CHEK2 protein expression by immunohistochemistry on a tissue microarray of 611 unselected breast tumors and also evaluated the tumor characteristics among 1,297 unselected breast cancer patients defined for the c.1100delC germ line mutation status (2.5% carrier frequency). CHEK2 protein expression was reduced in 21.1% of the unselected breast cancers studied. Tumors with reduced CHEK2 expression had more often larger primary tumor size (pT3-4; nominal significance p = 0.002) compared to tumors with normal staining. A similar trend for larger tumor size was seen among the 37 breast tumors from c.1100delC germ line mutation carriers. Tumors from c.1100delC mutation carriers were of higher grade than those of noncarriers (nominal significance p = 0.02). The c.1100delC germ line mutation also associated strongly with bilateral breast cancer. No significant correlation was seen between CHEK2 status and hormone receptor status, histology, lymph node status, or overall survival.
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PMID:Correlation of CHEK2 protein expression and c.1100delC mutation status with tumor characteristics among unselected breast cancer patients. 1547 4

The prognostic and predictive relevance of p53 immunoreactivity is used here as a tentative approach for defining more accurately the benefit of adjuvant hormonal therapy in postmenopausal node-positive breast cancer patients. Ninety-seven postmenopausal patients with axillary lymph node metastasis were treated with an antiestrogen for a period of 3 years after primary surgery and radiotherapy. The p53 status of the primary tumor was assessed by immunohistochemistry and 24% of the samples showed positive expression of p53. Within the average follow-up time of 59 months, disease recurrence was diagnosed in 34 patients (35%). Multivariate analysis showed high clinical stage, negative estrogen receptor status and p53 positivity to be independent prognostic factors predicting both shortened disease-free survival and worse overall survival. p53 immunoreactivity was associated with worse clinical outcome irrespective of hormone receptor status. The data suggest that adjuvant therapy with antiestrogens is insufficient in this patient population with p53-positive tumors.
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PMID:Adverse outcome and resistance to adjuvant antiestrogen therapy in node-positive postmenopausal breast cancer patients-The role of p53. 1600 29

The BRMS1 (breast cancer metastasis suppressor 1) gene has been found to suppress metastasis in animal models without inhibiting primary tumor growth. The aim of this study was to measure expression of BRMS1 mRNA in a panel of human breast carcinomas and compare its expression with parameters of local dissemination such as tumor size and lymph node metastasis. We also compared expression of BRMS1 mRNA in normal breast tissue, fibroadenomas, primary breast cancers and axillary nodal metastases from primary breast cancers. BRMS1 mRNA was detected in 10/11 (90%) specimens of normal breast tissue, 12/16 (75%) fibroadenomas, 64/82 (78%) primary breast cancer and 11/15 (64%) lymph node metastases (p, NS). In the primary cancer, expression was independent of tumor size, tumor grade, metastasis to axillary nodes and hormone receptor status. Furthermore, similar levels of BRMS1 were found in normal breast tissue, primary breast carcinomas and lymph node metastases from primary breast cancer. Our results do not suggest a role for BRMS1 in suppressing metastasis to local lymph nodes in patients with breast cancer.
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PMID:Expression of the breast cancer metastasis suppressor gene, BRMS1, in human breast carcinoma: lack of correlation with metastasis to axillary lymph nodes. 1600 75

Therapeutic effects of adjuvant therapies for breast cancer have been assessed "across the board" and implemented using the principle that if a treatment is effective "on average" then it is effective "for all patients." Exploration and improved understanding of the biological basis for predicting response to available adjuvant therapies is essential to enhance patient care. As illustration, we consider the effects of chemotherapy and tamoxifen in two International Breast Cancer Study Group (IBCSG) trials for postmenopausal women. The level of estrogen receptor (ER) expression in the primary tumor is a powerful predictor of response to adjuvant therapy. Absence of ER identifies a chemosensitive cohort for which concurrent tamoxifen significantly blunts the large chemotherapy effect. High levels of ER expression are associated with good results using tamoxifen alone; adding chemotherapy provides little additional benefit. By contrast, adding chemotherapy to tamoxifen provides additional benefit for patients with node-positive disease and tumors expressing intermediate levels of ER. Identification of chemosensitive targets, e.g., absence of PgR, in tumors with intermediate ER expression is required to further tailor, adding chemotherapy within this otherwise endocrine-responsive cohort. Age is not a therapeutic target. Thus, the biological bases for treatment responsiveness must be defined. All findings from clinical trials and meta-analyses should be presented primarily according to steroid hormone receptor status and future studies should be designed as tailored treatment investigations.
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PMID:Predicting response to systemic treatments: learning from the past to plan for the future. 1619 62

Metaplastic carcinoma of the breast, a neoplasm with both epithelial and mesenchymal elements, represents less than 1 per cent of all breast cancer. We reviewed the records of all patients diagnosed with localized metaplastic breast cancer from 1991 to 2003 at our institution. We identified 21 patients. Mean primary tumor size was 4.62 cm. Eight patients (38%) had axillary node involvement at presentation. All the tumors were high grade. Only two (10%) of the tumors were hormone receptor positive. Seventeen (81%) of the patients received adjuvant chemotherapy, and 12 (57%) of the patients received radiation. Ten (29%) patients suffered a local recurrence. With a mean follow-up of 46 months, the 5-year disease-free and overall survival was 42 per cent (95% CI: 20% to 65%) and 71 per cent (95% CI: 46% to 96%), respectively. Stage-specific overall survival was 100 per cent, 83 per cent, and 53 per cent for stages I, II, and III, respectively. By multivariate analysis, there was no impact on recurrence or survival with regard to size, age, menopausal status, nodal status, histologic subtype, adjuvant therapy, or extent of surgery. Metaplastic breast cancer is a unique neoplasm that tends to present at an advanced stage and has a propensity for local recurrence. When stratified by stage, however, survival appears similar to that of adenocarcinoma of the breast, and these tumors should be treated as such.
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PMID:Metaplastic breast cancer: clinical features and outcomes. 1646 6

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

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

The aim of this paper is to determine similarities and differences between tumor cell subclones in cases of ductal invasive breast carcinoma, and which occupy primary tumor and local axillary lymph metastases. The tumor growth fraction evaluated by Ki-67 was analyzed along with the expression level of estrogen and progesterone receptors, protein p53, proto-oncogene protein bcl-2 and cathepsin D in 60 patients. Metastatic lymph node in axilla has a higher growth fraction of the tumor cells than the primary tumor (p = 0.045), as well as the higher level of bcl-2 overexpression (p = 0.014). No statistically significant difference was found in the presence of immunohistochemically identified estrogen receptors (p = 0.161) and progesterone receptors (p = 0.081) between the primary tumor and the metastatic lymph node in axilla. Likewise, no difference was found between the immunohistochemical evaluation of p53 (p = 0.356) and cathepsin D activity (p = 0.928). A higher growth fraction of the tumor cells and the higher level of bcl-2 overexpression in metastatic tumor cells indicate the more aggressive cell subclones. This study does not support the routine testing of both primary tumor and locoregional metastasis to evaluate the breast cancer hormone receptor status.
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PMID:Tumor growth fraction, expression of estrogen and progesterone receptors, p53, bcl-2 and cathepsin D activity in primary ductal invasive breast carcinoma and their axillary lymph node metastases. 1821 56

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

In early breast cancer, excision of the primary tumor, with or without radiotherapy and adjuvant chemotherapy or tamoxifen, is highly effective and yields long-term disease control for many patients. Some patients relapse early (within 2 years of surgery); such relapses are predominantly distant metastases and are associated with an increased risk for breast cancer-related mortality. The aromatase inhibitors (anastrozole, letrozole, and exemestane) have been shown to be superior to tamoxifen in improving disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Anastrozole and letrozole are approved in the initial adjuvant setting, and their use appears to be a better option than initial tamoxifen for preventing disease recurrence in the first 2 years of therapy, the peak time for recurrence and metastases. This review compares the ability of aromatase to prevent early recurrences, particularly distant metastases.
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PMID:Reducing early recurrence with adjuvant aromatase inhibitors: what is the evidence? 1849 Jan 63


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