Prognostic significance of p53 overexpression in luminal HER2-negative type breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 35-35 ◽  
Author(s):  
Shoichi Kikuchi
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Tumor Size ◽  
Prognostic Significance ◽  
Nodal Status ◽  
Nuclear Grade ◽  
P53 Overexpression ◽  
Negative Type ◽  
Luminal Type ◽  
Significant Factors

35 Background: In this study, we evaluated the prognostic significance of p53 overexpression, because it was reported that there was a significant correlation between p53 and resistance to endocrine therapy, and prognosis. Methods: A retrospective analysis was performed using 2,332 primary breast cancer patients who underwent surgery between 2001 and 2010. There were 1,899 cases with luminal subtypes (905 cases: HER2-negative and Ki67 low type; 808 cases: HER2-negative and Ki67 high type; and, 186 cases: HER2-positive type), 155 cases with HER2-enriched subtypes, and 278 cases with triple-negative subtypes. Luminal type was defined as ER-positive cell rates ≥ 1%, regardless of PgR status. The cut-off value of the Ki67 index was 20%. Moreover, tumor size, nodal status and nuclear grade were studied in relation to disease free (DFS) and overall survival (OS) using the Cox proportional hazard model. Results: We found that p53 overexpression was present in 10% of the patients and significantly correlated with larger tumors, younger age, positive nodes, a higher grade, negative ER/PgR, a higher Ki67, and positive HER2. The patients with p53 overexpression had significantly unfavorable prognosis, especially in the patients who only received endocrine therapy. There were 26 cases in the luminal HER2 negative and Ki67 low type group that had p53 overexpression and showed a significantly shorter DFS. In the univariate analysis for DFS, p53, Ki67, tumor size, nuclear grade and nodal status were significant factors in luminal HER2 negative type. In the subsequent multivariate analysis for DFS, the p53 status was one of the most significant factors. Conclusions: The p53 overexpression was a significant prognostic factor in luminal type breast cancer. Therefore, the prognostic evaluation of luminal HER2 negative type breast cancer might be improved using an immunopanel, which includes Ki67 and p53. Moreover, it might isolate the patients who are resistant to endocrine therapy.

scholarly journals Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

2009 ◽  
Vol 27 (8) ◽  
pp. 1160-1167 ◽  
Author(s):  
Joel S. Parker ◽  
Michael Mullins ◽  
Maggie C.U. Cheang ◽  
Samuel Leung ◽  
David Voduc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Risk Score ◽  
Tumor Size ◽  
Pathologic Complete Response ◽  
Prognostic Significance ◽  
Intrinsic Subtype ◽  
Cancer Prognosis ◽  
Intrinsic Subtypes ◽  
Node Negative

Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. Conclusion Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.

Histologic Grade Remains a Prognostic Factor for Breast Cancer Regardless of the Number of Positive Lymph Nodes and Tumor Size: A Study of 161 708 Cases of Breast Cancer From the SEER Program

2014 ◽  
Vol 138 (8) ◽  
pp. 1048-1052 ◽  
Author(s):  
Arnold M. Schwartz ◽  
Donald Earl Henson ◽  
Dechang Chen ◽  
Sivasankari Rajamarthandan
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Lymph Nodes ◽  
Tumor Size ◽  
Nodal Status ◽  
Histologic Grade ◽  
Axillary Lymph Nodes ◽  
Low Grade ◽  
Axillary Lymph ◽  
Data Set

Context.—The appropriate staging of breast cancers includes an evaluation of tumor size and nodal status. Histologic grade in breast cancer, though important and assessed for all tumors, is not integrated within tumor staging. Objective.—To determine whether the histologic grade remains a prognostic factor for breast cancer regardless of tumor size and the number of involved axillary lymph nodes. Design.—By using a new clustering algorithm, the 10-year survival for every combination of T, N, and the histologic grade was determined for cases of breast cancer obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. There were 36 combinations of TN, defined according to the American Joint Committee on Cancer, and grade. Results.—For each combination of T and N, a categorical increase in the histologic grade was associated with a progressive decrease in 10-year survival regardless of the number of involved axillary lymph nodes or size of the primary tumor. Absolute survival differences between high and low grade persisted despite larger tumor sizes and greater nodal involvement, though trends were apparent with increasing breast cancer stage. Statistical significance depended on the number of cases for each combination. Conclusions.—Histologic grade continues to be of prognostic importance for overall survival despite tumor size and nodal status. Furthermore, these results seem to indicate that the assignment of the histologic grade has been consistent among pathologists when evaluated in a large data set of patients with breast cancer. The incorporation of histologic grade in TNM staging for breast cancer provides important prognostic information.

scholarly journals PO-0739: Role of ki67, tumor size and lymph nodal status as a prognostic index in breast cancer

2018 ◽  
Vol 127 ◽  
pp. S378-S379
Author(s):  
F. Arcadipane ◽  
S. Osella-Abate ◽  
A. Vella ◽  
P. Franco ◽  
S. Martini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Prognostic Index ◽  
Nodal Status

5162 Prognostic significance of breast cancer subtypes and nodal status

2009 ◽  
Vol 7 (2) ◽  
pp. 308-309
Author(s):  
J.M. Jurado ◽  
J.A. Ortega ◽  
P. Iglesias ◽  
E. Pacios ◽  
M. Delgado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Nodal Status ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes

High Levels of Cathepsin B Predict Poor Outcome in Patients with Breast Cancer

1998 ◽  
Vol 13 (3) ◽  
pp. 139-144 ◽  
Author(s):  
T.M. Maguire ◽  
S.G Shering ◽  
C.M. Duggan ◽  
E.W. McDermott ◽  
N.J. O'Higgins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Plasminogen Activator ◽  
Tumor Size ◽  
Cathepsin B ◽  
Nodal Status ◽  
Chi Square ◽  
Poor Outcome ◽  
Cancer Spread ◽  
Er Status

Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and metastasis. Other proteases involved in cancer spread such as urokinase-type plasminogen activator (uPA) and cathepsin D have previously been shown to be prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with primary breast cancer. CB levels were significantly higher in both primary and metastatic breast tumors than in fibroadenomas (p=0.0001). In the primary carcinomas, CB levels showed no significant correlation with either nodal status, tumor size or estrogen receptor (ER) status. Patients with primary breast cancers containing high levels of CB had a significantly shorter disease-free interval (p=0.01, chi-square=6.61) and overall survival (p=0.014, chi-square=6.08) than patients with low levels of the protease. However, in multivariate analysis, using nodal status, tumor size, ER status and urokinase plasminogen activator (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER status and uPA were prognostic in multivariate analysis. In conclusion, CB, like certain other proteases implicated in cancer metastasis, correlates with poor outcome in patients with breast cancer. These results thus support the evidence from model systems linking CB to cancer spread. Inhibition of CB expression or activity might therefore be exploited for anti-metastatic therapies.

The Optimal Duration and Selection of Adjuvant Endocrine Therapy for Breast Cancer: How Long Is Enough?

2014 ◽  
pp. e16-e24 ◽  
Author(s):  
Ian E. Smith ◽  
Belinda Yeo ◽  
Gaia Schiavon
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Prognostic Significance ◽  
Indirect Evidence ◽  
Late Recurrence ◽  
Term Treatment ◽  
Adjuvant Endocrine Therapy ◽  
Risk Of Recurrence ◽  
Long Term Treatment

Women with estrogen receptor (ER)+ early breast cancer (BC) are at continuing risk of relapse up to at least 15 years after diagnosis, despite being on adjuvant endocrine therapy for approximately 5 years. Extended adjuvant endocrine therapy with an aromatase inhibitor (AI) after 5 years of tamoxifen further reduces the risk of recurrence in postmenopausal women. More recently, continuing tamoxifen for 10 years has also been shown to further reduce the risk of recurrence compared with 5 years. There are no direct comparative data on the relative merits of extended tamoxifen compared with an AI; indirect evidence suggests that an AI may have increased efficacy but a greater adverse effect on quality of life. Results are awaited on the need for continuing front-line adjuvant AIs for more than 5 years. The next challenge is to determine which patients will benefit from this long-term treatment. Currently, tumor size, nodal involvement, and gene expression profile as measured by the PAM50 Risk of Recurrence (ROR) score have all been shown to have prognostic significance for late recurrence beyond 5 years.

scholarly journals The Numbers of FoxP3+ Lymphocytes in Sentinel Lymph Nodes of Breast Cancer Patients Correlate With Primary Tumor Size but Not Nodal Status

2011 ◽  
Vol 29 (6) ◽  
pp. 419-425 ◽  
Author(s):  
Raavi Gupta ◽  
James S. Babb ◽  
Baljit Singh ◽  
Luis Chiriboga ◽  
Leonard Liebes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Tumor Size ◽  
Primary Tumor ◽  
Sentinel Lymph Nodes ◽  
Nodal Status ◽  
Breast Cancer Patients ◽  
Primary Tumor Size

Persistence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients predicts increased risk for relapse—Results of pooled European data

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10083-10083 ◽  
Author(s):  
W. J. Janni ◽  
G. Wiedswang ◽  
T. Fehm ◽  
J. Jueckstock ◽  
E. Borgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Prognostic Significance ◽  
Primary Diagnosis ◽  
Nodal Status ◽  
Breast Cancer Patients ◽  
Increased Risk

10083 Background: The prognostic significance of DTC in the BM of breast cancer patients at the time of primary diagnosis has recently been confirmed by a large pooled analysis. If the persistence of DTC after adjuvant therapy confers a similar risk for relapse, there might be an indication for secondary adjuvant treatment. Methods: We analyzed BM aspirates of 697 patients from academic breast cancer units in Oslo (n=356), Munich (n=228) and Tuebingen (n=113) during recurrence-free follow-up at a median interval of 32.4 months (standard deviation [std] 19.4 mon) after primary diagnosis of breast cancer pT1–4, pN0–3 pM0. Carcinoma cells were detected using a standardized immunoassay with the monoclonal antibodies A45-B/B3 (Munich, Tuebingen), or AE1 and AE3 (Oslo), directed against cytokeratin (CK). Patients were followed for a median of 54.2 months (std 24.5 mon) after primary diagnosis. Results: Persistent DTC in the BM were detected in 15.6% of the patients (n=109). The Kaplan-Meier estimate for mean distant relapse-free survival estimate was 155.6 mon (142.4 - 168.9 95%CI) in patients with negative and 102.3 mon (93.6 - 111.0, 95% CI, p< .0001, log rank test) in patients with positive BM status. Patients without evidence of persistent DTC had a significantly longer overall survival (164.4 [155.6 - 173.3]), than patients with positive BM status (101.7 mon [89.4 - 113.9], p< .0001). In multivariate Cox regression analysis, allowing for bone marrow status, tumor size, nodal status, histopathological grading and hormone receptor status, DTC was of higher independent prognostic significance for subsequent reduced breast cancer specific survival (RR 5.9, 2.8 - 12.8, 95% CI, p< .0001), than nodal status at time of primary diagnosis (RR 1.2, 1.0 - 1.3, 95% CI, p=.014). Conclusion: Evidence of persistent DTC in breast cancer patients indicates an increased risk for subsequent relapse, and may serve for monitoring in future clinical trials. Such trials might investigate the benefit of individualized secondary adjuvant treatment or extended adjuvant therapy of patients with DTC. No significant financial relationships to disclose.

Late relapse associated with CEP 17 polysomic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20011-20011
Author(s):  
L. J. Theobald ◽  
S. Dobin ◽  
S. Beeran ◽  
D. Miltenburg ◽  
H. Rajab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Tumor Size ◽  
Nodal Status ◽  
Gene Copy ◽  
Categorical Variables ◽  
Late Relapse ◽  
Study Cohort ◽  
Breast Cancers ◽  
Clinicopathologic Factor

20011 Background: The clinicopathologic features associated with chromosome enumeration probe 17 (CEP 17) polysomy by fluorescence in situ hybridization (FISH) are not well defined. CEP 17 polysomy is frequently encountered in assessing Her-2neu amplification, which has become an important adjuvant therapeutic target. One mechanism to increase Her-2neu gene copy is polysomy. In this analysis the prognostic and predictive factors associated with CEP 17 polysomy are compared to similar factors in Her-2neu gene amplification. Methods: All cases of Her-2neu gene amplification and CEP 17 polysomic breast cancers from 2000 to present were abstracted. The polysomy group was defined as at least 3 gene copies and was further subdivided into two groups; 3–4 copies and ≥ 5 copies. This resulted in 193 cases of invasive breast cancer, which became the study cohort. Polysomic status and her-2neu gene amplification was compared to age, estrogen receptor (ER), progesterone receptor (PR), grade, tumor size, cell type, mitotic rate, nodal status, number of positive nodes and relapse. Descriptive statistics were used for categorical variables. The χ2 test was used to compare each clinicopathologic factor. Results: Both the ER and PR status was significantly different in the 3 groups. For the Her-2neu amplified, the polysomic 3–4, and the polysomic ≥ 5, the ER positive status was 53%, 67% and 81%, respectively (p = .012). Histologic grade, tumor size and nodal status were not significantly different between groups. Lobular pathology was present in 15% of the polysomy ≥ 5 group, 8% of the polysomy 3–4 group and 1.7% of the amplified group and this difference was significant (p = .03). Relapse disease status was significantly more frequent in the polysomy ≥ 5 group (18.5%) compared to the amplified group (2.6%) (p = .007). Within the relapsed group the median time to relapse was 4 years for the amplified patients versus 12 years and 10 years for the polysomic patients. Conclusion: The incidence of CEP 17 polysomy varies in the literature from 10–50% depending on definitions. Our study is unique in that we divided the polysomic group into 3–4 copies which can be complicated by proliferative activity versus ≥ 5 copies. A significant association between relapse and polysomic breast cancer is described in our dataset. No significant financial relationships to disclose.

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