Survival rates breast cancer with lymph node involvement 911,2011 ford edge cold air intake add,food garden home vet - Plans Download

Five-year disease-free survival curves according to the number of lymph node metastases by ultrasonography.
Five-year disease-free survival curves according to the number of lymph node metastases by histologic examination. Abstract Objective: To analyze the impact on prognosis of the number of axillary lymph node metastases (LNM) detected by ultrasound (US) in patients with breast cancer.
Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Kijima Y, Yoshinaka H, Hirata M, Mizoguchi T, Ishigami S, Nakajo A, Arima H, Ueno S, Natsugoe S. Morphologic features of tumour cells have long been validated for the clinical classification of breast cancers and are regularly used as a “gold standard” to ascertain prognostic outcome in patients. Tumours in the breast have long been classified according to their morphologic features, histologic type, and grade (severity). Most breast cancers originate from the inner (“luminal”) cells that line the mammary ducts. The mechanism or mechanisms by which basal-like breast cancer metastasizes to the brain is not currently clear. The normal breast–like tumours are those that do not fall into any of the other categories. Triple-negative breast cancer is a recent term derived from tumours that are characterized by the absence of er, pgr, and her2. If expression profiling analysis using the intrinsic gene list is considered the “gold standard” for identification, triple-negative tumours and a great preponderance of tumours overall do not express er, pgr, and her2 17, 34.
From a pathologist’s point of view, triple-negative tumours and basal-like tumours are predominantly of high histologic grade 23, 25, 26. The contribution of BRCA mutations to the development of breast cancer within any specific population depends on prevalence and penetrance power. Among triple-negative tumours, the incidence of BRCA1 or BRCA2 mutations was reported to be approximately 12.5%.
Patients with triple-negative breast cancer do not benefit from hormonal or trastuzumab-based therapies because of the loss of target receptors such as er, pgr, and her2. Mutations in the BRCA1 gene have been demonstrated to lead to error-prone dna repair, resulting in genomic instability and thus predisposition to carcinogenesis. Approximately 66% of breast cancer patients with triple-negative tumour cells and basal-like tumour cells have been reported to express egfr 17, 25, 64.
Numerous phase i and ii clinical trials for the treatment or management of patients with triple-negative breast tumours are under way.
Agents that damage DNA Drugs (such as cisplatinum 31, etoposide, and bleomycin) and ionizing radiation might control the proliferation of, and induce cell death in, triple-negative breast tumour cells. Agents that target EGFR Overexpression of egfr in triple-negative and basal-like tumour cells is well established 17, 25, 64. Agents that inhibit PARP1 Phase i clinical trials using parp1 inhibitors have been successfully completed, and phase ii studies have begun. Agents that inhibit c-Kit The efficacy of imatinib, a drug that inhibits c-Kit tyrosine kinase, is being evaluated in patients with triple-negative and basal-like tumours. Triple-negative cancers are reported to respond to neoadjuvant chemotherapy 9, 66, 69, but overall, survival in patients with such tumours is still poor, and management of these patients may require more aggressive intervention. This work was supported in part by grant RO1 CA118089 (to KBR) from the National Institutes of Health and by the Department of Pathology, Wayne State University. This lymph node (arrow) shows clearly defined boundaries but scattered large internal echoes accompanied by notching.
Methods: One-to-one comparison of LNM was performed between the ultrasound and histologic diagnosis in 380 patients.
Number of Axillary Lymph Node Metastases Determined by Preoperative Ultrasound is Related to Prognosis in Patients with Breast Cancer. Identification of molecular markers such as expression of the receptors for estrogen (er) and progesterone (pgr) and the human epidermal growth factor receptor 2 (her2) has played an important role in determining targets for the development of efficacious drugs for treatment and has also offered additional predictive value for the therapeutic assessment of patients with breast cancer. Identification of molecular markers such as expression of the estrogen (er) and progesterone receptors (pgr) and the human epidermal growth factor receptor 2 (her2) has offered additional predictive value for the therapeutic assessment of women diagnosed with breast cancer 1– 4.
Luminal A and luminal B tumours are similar in that both are typically er+ or pgr+, or both. They tend to have the best prognosis, with relatively high rates of overall survival and relatively low rates of recurrence. However, the incidence of brain metastasis among patients with her2+ or cytokeratin 14 tumours has been documented 18, 19. Triple-negative disease is diagnosed more frequently in younger and premenopausal women 11, 23– 26 and is highly prevalent in African American women 27, 28.
In about 60% of cases, these tumour cells express the receptor for epidermal growth factor (egfr) 17, 30– 32 and may also contain mutations in the p53 gene 10, 11, 33. However, among basal-like tumours, 5%–45% were reported to be er+, and 14% were shown to be her2+ 9.
However, individuals carrying mutations in the BRCA gene (BRCA1 or BRCA2) have a 40%–80% chance of developing breast cancer.
Mutations in the BRCA1 and BRCA2 genes occur with different frequencies in individuals of different ethnicities living in different geographic regions in the world. Hence, surgery and chemotherapy, individually or in combination, appear to be the only available modalities.
This phenomenon could be relevant to the control of proliferation in brca1-related, triple-negative, and basal-like tumour cells.
The high priority of these agents is based on the brca1 pathway and dna repair dysfunction seen in triple-negative breast cancer, which may confer enhanced sensitivity to agents that damage dna. At least a couple of phase ii clinical trials are using cetuximab (antibody treatment), which targets the expression of egfr or its signalling pathways.



The data from these studies have already indicated that parp1 inhibitors could protect against the nephrotoxicity of cisplatin and the cardiotoxicity of doxorubicin 67, 68, thus potentially helping to provide additional chemotherapeutic efficacy. However, the immunohistochemical detection of c-Kit overexpression does not guarantee a positive response to imatinib in patients with metastatic disease because most commercially available antibodies for c-Kit recognize total c-Kit and do not distinguish the activated or phosphorylated version, which is the actual target of imatinib. The data obtained from various investigations using triple-negative tumour cells suggest that patients with these breast cancers are more likely to benefit from chemotherapeutic agents in development that use a strategy of inhibiting dna repair. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients. Immunolocalization of a human basal epithelium specific keratin in benign and malignant breast disease. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Basal-like grade iii invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival.
Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma.
Phase ii trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2–positive breast cancer.
Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer.
Descriptive analysis of estrogen receptor (er)–negative, progesterone receptor (pr)–negative, and her2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Centrally necrotizing carcinomas of the breast: a distinct histologic subtype with aggressive clinical behavior. Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from calgb 9342. BRCA2 in American families with four or more cases of breast or ovarian cancer: recurrent and novel mutations, variable expression, penetrance, and the possibility of families whose cancer is not attributable to BRCA1 or BRCA2. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Spectrum and prevalence of BRCA1 and BRCA2 germline mutations in Sardinian patients with breast carcinoma through hospital-based screening. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the dna cross-linking agent cisplatin. Homology-directed dna repair, mitomycin-C resistance, and chromosome stability is restored with correction of a BRCA1 mutation. Exploiting the dna repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer.
Specific killing of BRCA2-deficient tumours with inhibitors of poly(adp–ribose) polymerase. Metaplastic breast carcinomas exhibit egfr, but not her2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis. More recent technical advancements in identifying several cancer-related genes have provided further opportunities to identify specific subtypes of breast cancer.
More recently, gene expression analysis using dna microarray technology has identified additional breast tumour subtypes that were not apparent using traditional histopathologic methods.
However, they are dissimilar in that the A type is usually her2– and the B type is more likely to be her2+ and lymph node–positive.
Those with luminal B tumours tend to have a higher tumour grade and a poorer prognosis 10, 11 (Table i). These tumours are diagnosed more frequently among younger women and are associated with hereditary BRCA1-related breast cancers. Data developed by sequencing primary breast tumours, brain metastases, matched normal tissue, and a mouse xenograft developed from the primary tumour identified 50 point mutations and small insertions or deletions that were present in the tumour genomes but not in the matched normal tissue 20.
It remains unclear whether this racial association is related to germ-line genetic factors, exposure to environmental factors, or a combination of both. Furthermore, during investigations of the expression of basal cks and egfr in separate cohorts of triple-negative tumours, only 56%–84% expressed those markers 25, 26.
Thus, identification of BRCA mutations has been used as one of the strongest breast cancer predictors 38– 41. For example, 64% of high-risk families in Poland are reported to carry BRCA1 mutations (1 in 9 are recurring mutations), but rarely any BRCA2 mutations 45. In some triple-negative tumours of high histologic grade, brca1 protein levels have been shown to be significantly lower, suggesting that the brca1 pathway may be dysfunctional in these tumour cells 50, 52. However, some studies have identified certain receptors as targets for new therapeutic drugs—for example, cell-surface receptors such as egfr and c-Kit, both of which have been shown to play a major role in the progression of triple-negative tumours. Data from several in vitro studies have indicated that breast tumour cells with BRCA1 mutations are extremely sensitive to drugs that induce cross links (mitomycin-C and platinum) and single- and double-strand breaks (etoposide and bleomycin) in dna 56– 58. Clinical trials evaluating the efficacy of humanized anti-egfr monoclonal antibodies and egfr tyrosine kinase inhibitors in patients with triple-negative breast cancer are currently under way 65.
The parp1 inhibitors effectively disarm the ability of cancer cells to repair themselves and cause the death of those cells. Vijaylaxmi (The University of Texas Health Science Center at San Antonio, San Antonio, TX) for helpful discussions.


According to the subdivision of number of LNM (0, 1–3, 4–9, 10+), the accuracy rates associated with LNM were 82%, 49%, 34%, and 86%, respectively. Among the subtypes, tumours with triple-negative cells are identified using specific staining procedures for basal markers such as cytokeratin 5 and 6 and the absence of er, pgr, and her2 expression.
They are often aggressive 15– 17 and are associated with a prognosis poorer than those for the luminal A, luminal B, and normal breast–like types 11, 16. The her2+ tumours have relatively poor prognoses and are prone to early and frequent relapse and to distant metastasis 11, 16, 22. In addition, patients with triple-negative tumours that express a basal-like tumour phenotype have a significantly shorter disease-free survival than do patients with triple-negative tumours lacking the expression of basal-like tumour markers 25, 26.
By contrast, the incidence of sporadic mutations in BRCA1 and BRCA2 are in the ranges 4%–29% and 0.6%–16% respectively 39. In Sweden, 34% of high-risk families carry BRCA1 mutations, but only 2% carry BRCA2 mutations 46. Several lines of evidence suggest a link between basal-like breast cancer and brca1 deficiency 51. Furthermore, single-strand breaks in dna are repaired by the base-excision repair pathway in which poly(adp–ribose) polymerase 1 (parp1) enzyme is one of the essential components.
Oncology Research, is evaluating weekly gefitinib (Iressa: AstraZeneca) plus carboplatin, with or without cetuximab, in treating patients with metastatic breast cancer. Importantly, parp inhibition, which kills cancer cells, spares identical normal cells that lack cancer-related alterations such as those from mutated BRCA1 and BRCA2. Patients with triple-negative breast cancers therefore have the disadvantage of not benefiting from currently available receptor-targeted systemic therapy. Metastatically, they seems to disseminate to the axillary nodes and, less frequently, to bone 18.
When triple-negative and basal-like tumours were analyzed by gene expression profiling, 71% of triple-negative tumours showed a basal-like phenotype, and 77% of basal-like tumours showed a triple-negative phenotype 35. Among triple-negative tumours, most recurrences are observed during the 1st and 3rd years after therapy. By contrast, 32% of high-risk Sardinian families carry mutations in BRCA2, and 11%, mutations in BRCA1 47. The functions of brca1 are diverse, and one is the repair of double-stranded dna breaks by the potentially error-free mechanism of homologous recombination 50. 17 observed the expression of c-Kit in 31% of basal-like tumour cells and also in 11% of non-basal-like tumour cells. Cells null for brca1 were shown to be incapable of repairing dna strand breaks 59, and inhibition of parp1 resulted in enhanced apoptotic processes 60, 61. In combination with chemotherapy, parp1 inhibitor (BSI-201) shows promise in the treatment of triple-negative tumours not harbouring BRCA mutations.
Conclusion: Preoperative ultrasound can determine axillary involvement and may be useful for predicting prognosis.
Optimal conditions for the therapeutic assessment of women with triple-negative breast tumours and for the management of their disease have yet to be validated in prospective investigations.
In a population-based study, basal-like breast cancer was suggested to be more prevalent among premenopausal African American women (39% vs.
Although the terminology relating to triple-negative and basal-like tumours tends to be used interchangeably, it is not entirely interchangeable or synonymous. Most deaths take place in the first 5 years, even after a strict therapeutic regimen 23, 26. Interestingly, dna microarray and immunohistochemical analyses revealed that 80%–90% of breast cancers in women with germ-line mutations in BRCA1 are triple-negative (er–, pgr–, her2–) 26, 48– 52.
Lack of brca1 could result in dna repair by more error-prone mechanisms such as nonhomologous end-joining and single-strand annealing, resulting in genomic instability and therefore cancer predisposition 53.
In addition, some available reports suggest that because brca1 deficient breast tumours share features and behavior associated with the basal-like tumours, the therapies that effectively target basal-like tumours should also be highly effective in the treatment of brca1-deficient breast cancer and triple-negative tumours.
The present review discusses the differences between triple-negative breast tumours and basal-like breast tumours and also the role of mutations in the BRCA genes.
Additional data also suggest that, compared with control patients having non-basal-like or non-triple-negative tumours, patients with triple-negative tumours and basal-like tumours experience significantly shorter survival after the first metastatic event 18, 23, 37. The extent to which the BRCA1 pathway contributes to the behavior of triple-negative cancers is an area of active research. Most BRCA1-associated tumours are triple-negative, and the patients in which they arise have a poor outcome 54. By contrast, these cells were shown to be resistant to mitotic-spindle poisons such as taxanes and vinorelbine 62.
Attention is also paid to treatment options available to patients with triple-negative breast tumours. Although triple-negative tumours and basal-like tumours share some characteristics, a careful analysis of microarray-based expression profiles suggests that triple-negative tumours also encompass phenotypes of normal breast–like tumours, and in most studies, normal breast–like tumours have been shown to cluster together with basal-like and her2 tumours in the er-negative arm 6, 8, 16, 22. Clustering analyses of microarray expression profiling data have shown that familial BRCA1 mutant tumours tend to fall into a basal-like category, suggesting similar carcinogenic pathways or causes in these cancer subtypes 55. Previous observations provided strong circumstantial evidence that the brca1 and parp1 pathways could be dysfunctional in a significant subgroup of triple-negative and basal-like breast tumours and, therefore, that those pathways could be targeted for therapy 60, 63. Because ionizing radiation also induces dna strand breaks, additional local or regional radiotherapy may possibly be of particular benefit for patients with triple-negative cancer. In addition, drugs such as carboplatin, cisplatin, parp1 inhibitors, and docetaxel could be very useful in the management of patients with advanced triple-negative cancers.



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