Article

Breast Cancer Subtypes Based on ER/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival

Department of Hematology/Oncology, Marshfield Clinic Weston Center, Weston, Wisconsin 54401, USA.
Clinical Medicine &amp Research 07/2009; 7(1-2):4-13. DOI: 10.3121/cmr.2009.825
Source: PubMed

ABSTRACT To compare the clinicopathologic features and survival in the four breast cancer subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2-; ER/PR-, Her2+; and ER/PR-, Her2-.
A 7-year retrospective study of 1134 invasive breast cancer subjects. Clinical and pathologic features and survival of the four subtypes were compared.
Using ER/PR+ and Her2- as a reference, ER/PR-, Her2- had the worst overall survival (hazard ratio, 1.8; 95% confidence interval [CI], 1.06-3.2) and the worst disease-free survival (hazard ratio, 1.5; 95% CI, 0.8-3.0). In ER/PR+, Her2-, chemotherapy conferred significant overall and disease-free survival advantages. Subtype comparison revealed statistically significant differences in outcomes.
The triple negative subtype has the worst overall and disease free survival. Efforts should be directed at standardization of current testing methods and development of more reliable and reproducible testing.

0 Followers
 · 
215 Views
  • Source
    • "Therefore, they present clinical challenge because they do not respond to endocrine therapy or other available therapies . Furthermore, this subtype of breast cancers shows overall worst or disease free survival [39]. Therefore, compound 5a could Table 1 Anti-proliferative capacity of novel indole retinoid derivatives (5(aee)) evaluated by SRB assay in different types of cancer cell lines. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, novel (E)-3-(5-substituted-1H-indol-3-yl)-1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)prop-2-en-1-one (5(a-e)) derivatives were synthesized and their anticancer effects were determined in vitro. Novel indole retinoid compounds except 5e have anti-proliferative capacity in liver, breast and colon cancer cell lines. This anti-proliferative effect was further analyzed in breast cancer cell line panel by using the most potent compound 5a. It was determined that 5a can inhibit proliferation at very low IC(50) concentrations in all of the breast cancer cell lines. Here, we present some evidence on apoptotic termination of cancer cell proliferation which may be primarily driven by the inhibition of RXRα and, to a lesser extent, RXRγ.
    European Journal of Medicinal Chemistry 10/2012; 58C:346-354. DOI:10.1016/j.ejmech.2012.10.013 · 3.43 Impact Factor
  • Source
    • "Ultimately, information derived from studies using this model may not be applicable to clinical B-TNBC. With these limitations in mind, we sought to establish a bona fide B-TNBC model that would comply with the following requirements: 1) lack of ER/PR/HER2 as a general marker of all TNBC subtypes; 2) lack of vimentin that is expressed in myoepithelial but not basal epithelial cells [45]; 3) expression of basal cytokeratins 5, 6, 14, and 17 as clear evidence for basal origin [46]; 4) ability to grow at the orthotopic site in mice [i.e., mammary fat pad (MFP)]; 5) ability to spontaneously metastasize from the orthotopic site to LNs and visceral organs mimicking the high metastatic potential of B-TNBC [6] [11]; 6) and lastly, ability to initially respond to cytotoxic therapy followed by rapid recurrence, as a well-documented feature of clinical B-TNBC [47]. After extensive search and several pilot studies with different lines, we determined that the HCC1806 cell line complies with all of the above requirements. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The basaloid triple-negative breast cancer (B-TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Current models do not recapitulate the basaloid phenotype of TNBC, thus limiting the understanding of its biology and designing new treatments. We identified HCC1806 as a line expressing typical B-TNBC markers, engineered a subline with traceable reporters, and determined growth, drug sensitivity, recurrence, and vascular and metastatic patterns of orthotopic xenografts in immunodeficient mice. mRNA and protein analyses showed that HCC1806 expresses basal but not luminal or mesenchymal markers. HCC1806-RR subline stably expressing red fluorescent protein and Renilla luciferase was generated and characterized for sensitivity to chemodrugs, orthotopic growth, vascular properties, recurrence, metastasis, and responsiveness in vivo. The HCC1806 cells were highly sensitive to paclitaxel, but cytotoxicity was accompanied by pro-survival vascular endothelial growth factor-A loop. In vivo, HCC1806-RR tumors display linear growth, induce peritumoral lymphatics, and spontaneously metastasize to lymph nodes (LNs) and lungs. Similarly to human B-TNBC, HCC1806-RR tumors were initially sensitive to taxane therapy but subsequently recur. Bevacizumab significantly suppressed recurrence by 50% and reduced the incidence of LN and pulmonary metastases by, respectively, 50% and 87%. The HCC1806-RR is a new model that expresses bona fide markers of B-TNBC and traceable markers for quantifying metastases. Combination of bevacizumab with nab-paclitaxel significantly improved the outcome, suggesting that this approach can apply to human patients with B-TNBC. This model can be used for defining the metastatic mechanisms of B-TNBC and testing new therapies.
    Neoplasia (New York, N.Y.) 10/2012; 14(10):926-42. DOI:10.1593/neo.12956 · 5.40 Impact Factor
  • Source
    • "org). This static level is disappointing when compared with cancers such as breast cancer, where earlier diagnosis and tailored therapies have lead to steep falls in mortality rates [6]. One of the most important determinants of ovarian cancer survival is early stage diagnosis; however, indications are very subtle and can be easily overlooked due to the unspecific nature of the symptoms of the condition [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoantibodies represent an attractive biomarker for diagnostic assays principally due to the stability of immunoglobulin in patient serum facilitating measurement with conventional assays. Immune responses to tumorigenesis may facilitate detection of ovarian cancer in the early stages of the disease with identification of a panel of tumour specific autoantibodies. Despite the reporting of many tumour associated autoantibodies using arrays of tumour antigens, this has not led to the advance in diagnostic capability as rapidly as was initially expected. Here we examine the potential diagnostic utility of candidate autoantibody biomarkers identified via screening of serum samples on a high content human protein array from a unique cohort of early stage and late stage ovarian cancer patients. We analyse the performance of autoantibodies to the tumour suppressor protein p53 and the novel autoantigens alpha adducin and endosulfine alpha identified in our array screen. Each antigen has different performance characteristics using conventional ELISA format and Western blot immunoassay. The high attrition rate of promising autoantigens identified by array screening can in part be explained by the presentation of the epitope of the antigen in the subsequent method of validation and this study provides directions on maximising the potential of candidate biomarkers. This article is part of a Special Issue entitled: Translational Proteomics.
    Journal of proteomics 03/2012; 75(15):4668-75. DOI:10.1016/j.jprot.2012.02.031 · 3.93 Impact Factor
Show more

Preview

Download
4 Downloads
Available from