p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

1996 ◽  
Vol 14 (5) ◽  
pp. 1604-1610 ◽  
Author(s):  
R Silvestrini ◽  
E Benini ◽  
S Veneroni ◽  
M G Daidone ◽  
G Tomasic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Mitochondrial Protein ◽  
Axillary Node ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Prognostic Information ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Node Positive

BACKGROUND AND PURPOSE The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

Activation (Tyrosine Phosphorylation) of ErbB-2 (HER-2/neu): A Study of Incidence and Correlation With Outcome in Breast Cancer

2000 ◽  
Vol 18 (18) ◽  
pp. 3230-3239 ◽  
Author(s):  
A.D. Thor ◽  
S. Liu ◽  
S. Edgerton ◽  
D. Moore ◽  
K.M. Kasowitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Cellular Proliferation ◽  
Multivariate Analyses ◽  
Receptor Activation ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Cellular Expression ◽  
Her 2

PURPOSE: We hypothesize that phosphorylated ErbB-2 (P-ErbB-2, identified by a novel antibody PN2A) may provide either more significant or additional prognostic marker data for breast cancer patients. This study was designed to compare the incidence and prognostic value of ErbB-2 (HER-2/neu) and P-ErbB-2 immunoexpression in archival breast cancer samples. MATERIALS AND METHODS: Eight hundred sixteen invasive breast cancers with a median of 16.3 years of follow-up were immunostained for ErbB-2 (using antibody CB11) and P-ErbB-2 (using antibody PN2A). ErbB-2 and P-ErbB-2 data were compared with clinical, histologic, immunohistochemical, and outcome variables. RESULTS: Of 816 primary breast cancers, 307 (38%) were positive for ErbB-2 and 37 (12% of ErbB-2 positive and 5% of the study population) expressed P-ErbB-2. P-ErbB-2 was not detected in ErbB-2–negative cases (n = 509). ErbB-2 immunohistochemical data were bimodal; patients with ≥ 80% cellular expression had the shortest disease-free and disease-specific survival. P-ErbB-2 was associated with a higher percentage of ErbB-2–positive cells, a higher number of positive lymph nodes, and cellular proliferation. ErbB-2 and P-ErbB-2 were indicators of poor prognosis in node-positive patients in both univariate and multivariate analyses. We found that either P-ErbB-2 expression or high (≥ 80%) ErbB-2 expression provided the most significant prognostic value in node-positive cases by multivariate analyses. There were too few P-ErbB-2–positive cases and events in the node-negative patient group to allow statistical analysis of P-ErbB-2 in that subgroup. CONCLUSION: PN2A immunostaining identified a subset (approximately 12% of ErbB-2–positive breast cancers) with activation (phosphorylation) of the receptor ErbB-2. P-ErbB-2 expression was strongly associated with higher levels of ErbB-2 expression (≥ 80%), although it was not a surrogate. Identification of cases with a high percentage of invasive breast cancer cells expressing ErbB-2 or determination of receptor activation via P-ErbB-2 may provide additional prognostic value in node-positive breast cancers.

scholarly journals p53 Expression in Node-Positive Breast Cancer Patients: Results from the Cancer and Leukemia Group B 9344 Trial (159905)

2011 ◽  
Vol 17 (15) ◽  
pp. 5170-5178 ◽  
Author(s):  
Jonathan F. Lara ◽  
Ann D. Thor ◽  
Lynn G. Dressler ◽  
Gloria Broadwater ◽  
Ira J. Bleiweiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
P53 Expression ◽  
Node Positive ◽  
Group B ◽  
Leukemia Group ◽  
Positive Breast Cancer

Enzyme-Linked Immunosorbent Assay of C-Erbb-2 Oncoprotein in Breast Cancer

1992 ◽  
Vol 38 (8) ◽  
pp. 1471-1474 ◽  
Author(s):  
A Nugent ◽  
E McDermott ◽  
K Duffy ◽  
N O'Higgins ◽  
J J Fennelly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Immunosorbent Assay ◽  
Normal Breast ◽  
Axillary Node ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancers ◽  
Prognostic Information ◽  
Breast Cancer Metastases ◽  
High Concentrations

Abstract Amplification or increased expression of the c-erbB-2 gene has previously been reported to be a prognostic marker for breast cancer. Gene amplification is usually measured by Southern blotting, whereas increased protein expression is usually detected by immunocytochemistry. We measured c-erbB-2 protein with an enzyme-linked immunosorbent assay (ELISA). High concentrations of oncoprotein were found in 25 of 161 (16%) primary breast cancers and in 3 of 6 (50%) breast cancer metastases. High concentrations were not found in normal breast tissue or benign breast tumors. In the primary cancers, high concentrations of c-erbB-2 protein were found more frequently (a) in estrogen receptor-negative tumors than in estrogen receptor-positive tumors, (b) in progesterone receptor-negative tumors than in progesterone-positive tumors, and (c) in axillary node-positive cancers than in node-negative cancers. Patients with tumors containing high amounts of the c-erbB-2 protein had a significantly shorter (P less than 0.001) disease-free interval and overall survival rate than did patients with low amounts. We conclude that assay of c-erbB-2 protein by ELISA is simple, rapid, and quantitative and offers important prognostic information in breast cancer.

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer.

1990 ◽  
Vol 8 (8) ◽  
pp. 1321-1326 ◽  
Author(s):  
R Silvestrini ◽  
M G Daidone ◽  
P Valagussa ◽  
G Di Fronzo ◽  
G Mezzanotte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Indicator ◽  
Axillary Node ◽  
Labeling Index ◽  
Nodal Involvement ◽  
Prognostic Information ◽  
Node Positive ◽  
Thymidine Labeling Index ◽  
Definition Of ◽  
Positive Breast Cancer

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.

scholarly journals The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
J. L. Schwartz ◽  
A. N. Shajahan ◽  
R. Clarke
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Cell Fate ◽  
Interferon Regulatory Factor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Regulatory Factor ◽  
Inhibition Of Proliferation ◽  
P53 Expression ◽  
Interferon Regulatory Factor 1

Resistance to endocrine therapy is common among breast cancer patients with estrogen receptor alpha-positive (ER+) tumors and limits the success of this therapeutic strategy. While the mechanisms that regulate endocrine responsiveness and cell fate are not fully understood, interferon regulatory factor-1 (IRF1) is strongly implicated as a key regulatory node in the underlying signaling network. IRF1 is a tumor suppressor that mediates cell fate by facilitating apoptosis and can do so with or without functional p53. Expression of IRF1 is downregulated in endocrine-resistant breast cancer cells, protecting these cells from IRF1-induced inhibition of proliferation and/or induction of cell death. Nonetheless, when IRF1 expression is induced following IFNγtreatment, antiestrogen sensitivity is restored by a process that includes the inhibition of prosurvival BCL2 family members and caspase activation. These data suggest that a combination of endocrine therapy and compounds that effectively induce IRF1 expression may be useful for the treatment of many ER+ breast cancers. By understanding IRF1 signaling in the context of endocrine responsiveness, we may be able to develop novel therapeutic strategies and better predict how patients will respond to endocrine therapy.

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