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.

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.

Electrophoretic analysis of 248 clinical breast cancer specimens for P-glycoprotein overexpression or gene amplification.

1989 ◽  
Vol 7 (8) ◽  
pp. 1129-1136 ◽  
Author(s):  
D E Merkel ◽  
S A Fuqua ◽  
A K Tandon ◽  
S M Hill ◽  
A U Buzdar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Gene Amplification ◽  
Multiple Drug Resistance ◽  
Electrophoretic Analysis ◽  
Gene Copy ◽  
Cross Resistance ◽  
Glycoprotein Gene ◽  
P Glycoprotein ◽  
Clinical Breast

Multiple drug resistance (MDR), consisting of acquired cross resistance to anthracyclines, vinca alkyloids, and other antineoplastic antibiotics, has been described in a variety of cell lines. This MDR phenotype is associated with overexpression and sometimes amplification of a gene coding for a 170 kDa glycoprotein, termed P-glycoprotein. To understand the role of this mechanism in clinical breast cancer, 248 breast cancer specimens representing both untreated primary and refractory relapsing disease were probed for evidence of P-glycoprotein gene amplification or overexpression using Southern, Northern, or Western blot techniques. In no case was an increase in P-glycoprotein gene copy number or expression detected. Though these findings do not necessarily rule out a role for P-glycoprotein in mediating drug resistance in breast cancer, electrophoretic analysis of clinical specimens is unlikely to provide useful predictive information. More sensitive assays must be developed to overcome the difficulties inherent in analyzing heterogenous tissue samples.

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

HER-2/neu Analysis in Archival Tissue Samples of Human Breast Cancer: Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization

2001 ◽  
Vol 19 (2) ◽  
pp. 354-363 ◽  
Author(s):  
Annette Lebeau ◽  
Daniela Deimling ◽  
Christine Kaltz ◽  
Andrea Sendelhofert ◽  
Anette Iff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Paraffin Sections ◽  
Tissue Samples ◽  
Her 2

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.

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.

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

scholarly journals Gene Expression Profile Analysis of T1 and T2 Breast Cancer Reveals Different Activation Pathways

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Margit L. H. Riis ◽  
Xi Zhao ◽  
Fateme Kaveh ◽  
Hilde S. Vollan ◽  
Anne-Jorunn Nesbakken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Profile Analysis ◽  
Distant Metastases ◽  
Molecular Signature ◽  
Receptor Interaction ◽  
Lymph Node Status ◽  
Breast Cancers ◽  
Significant Difference ◽  
T1 And T2

Breast cancers today are of predominantly T1 (0.1≥2.0 cm) or T2 (>2≤5 cm) categories due to early diagnosis. Molecular profiling using microarrays has led to the notion of breast cancer as a heterogeneous disease both clinically and molecularly. Given the prognostic power and clinical use of tumor size, the purpose of this study was to search for molecular signatures characterizing clinical T1 and T2. In total 46 samples were included in the discovery dataset. After adjusting for hormone receptor status, lymph node status, grade, and tumor subclass 441 genes were differently expressed between T1 and T2 tumors. Focal adhesion and extracellular matrix receptor interaction were upregulated in the smaller tumors while p38MAPK signaling and immune-related pathways were more dominant in the larger tumors. The T-size signature was then tested on a validation set of 947 breast tumor samples. Using the T-size expression signatures instead of tumor size leads to a significant difference in risk for distant metastases (P<0.001). If further confirmed, this molecular signature can be used to select patients with tumor category T1 who may need more aggressive treatment and patients with tumor category T2 who may have less benefit from it.

SEER study of breast cancer specific mortality (BCSM) in patients with lobular tumors treated based on recurrence score results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11568-11568
Author(s):  
Frederick L. Baehner ◽  
Steven Shak ◽  
Dave P. Miller ◽  
Valentina I. Petkov
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Tumor Grade ◽  
Nodal Status ◽  
Large Sample Size ◽  
Lobular Breast Cancer ◽  
Gene Assay ◽  
Actuarial Methods

11568 Background: Linking the 21-gene assay RS result to the SEER Registries demonstrated very low 5-y BCSM with low RS and high 5-y BCSM with high RS across subgroups, such as nodal status, age, tumor size and grade (npj Breast Cancer 2016). Given the large sample size and interest in outcomes as a function of tumor characteristics, we characterized the relationship between RS results and BCSM in patients reported by SEER with lobular morphology. Methods: Patients with RS and lobular morphology based on the registry ICD-O-3 code 8520 were eligible if node negative (N0) or node positive up to 3 positive nodes (N+mic,1-3), HR+, HER2- negative, no prior malignancy, and diagnosed between Jan 2004 and Dec 2012. No information in SEER is available regarding lobulars, ie., trabecular, alveolar, solid and pleomorphic. 5-y BCSM was estimated using actuarial methods. Results: There were 6,075 eligible patients reported with lobular morphology (11% of cases). Median age was 59 years; 88%/12% were N0/N+; 31%/62%/7% grade 1/2/3; 61%/39% ≤2 cm/>2 cm. Median follow-up was 44 months. A minority (8%) had RS >25. Chemotherapy (CT) use and BCSM increased with increasing RS. In multivariable analysis in N0 disease, continuous RS result and tumor size predicted BCSM (p=0.003 and p=0.04, respectively), whereas age and tumor grade were non-significant. In multivariable analysis in N+ disease, continuous RS result alone predicted BCSM (p=0.002). Conclusions: In these analyses the prognosis of patients with lobular breast cancer treated based on RS results depends on both nodal status and the RS result. The 5-y BCSM for lobular breast cancer is excellent with RS of 25 or less, and increases for RS >25. [Table: see text]

Value of clinical treatment score post-5 years (CTS5) for late relapse risk assessment in patients with early-stage HER2+ breast cancer (BC) in the north central cancer treatment group (NCCTG) N9831 (Alliance) trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 529-529
Author(s):  
Tanmayi Pai ◽  
Angelica Gil ◽  
Yaohua Ma ◽  
Zhuo Li ◽  
Pooja Advani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Tumor Size ◽  
Cox Regression ◽  
Early Stage ◽  
Low Risk ◽  
Late Relapse ◽  
Intermediate Risk ◽  
Relapse Risk ◽  
Significant Difference

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .

scholarly journals Assessment of Breast Cancer Immunohistochemical Properties with Demographics and Pathological Features; A Retrospective Study

2021 ◽  
Vol 14 (11) ◽  
Author(s):  
Vahid Ariabod ◽  
Maryam Sohooli ◽  
Ramin Shekouhi ◽  
Kiana Payan
Keyword(s):  
Breast Cancer ◽  
Tumor Size ◽  
Tumor Grade ◽  
Histological Type ◽  
Tumor Diameter ◽  
Breast Cancers ◽  
Luminal A ◽  
Cross Sectional ◽  
Familial History ◽  
Female Population

Background: Breast cancer is considered the most common malignant disease in the female population. It is known as an emerging epidemy with a great burden on women's health, which can be associated with poor outcomes. Some factors including histological type, immunohistochemistry (IHC), tumor grade, and tumor size can have effects on breast cancer. Objectives: This study aimed at assessing the effects of mentioned factors on IHC type of breast cancer. Methods: This retrospective cross-sectional study was conducted on 142 patients, who were referred to one of the referral centers for breast cancer in Mashhad. Information including age, histological type, familial history, menopause status, tumor grade, tumor size, and IHC properties was collected from the patient’s medical records. Allred score was used for reporting hormonal status. The data were analyzed by version 26 of SPSS software. Results: The mean age of patient was 50.2 ± 12.7. The frequency of luminal A and luminal B type was calculated as 29.7 and 18.9%, respectively. In addition, triple-negative IHC type has a prevalence of 24.3% and HER2 had a prevalence of 27%. There were no significant differences between age (P = 0.34), familial history (P = 0.42), menopause (P = 0.36), histological type (invasive: P = 0.11, in situ: P = 0.45), and IHC properties. However, tumor diameter (P = 0.0001) and tumor grading (P = 0.002) had significant association with IHC properties. Conclusions: Factors including tumor size and pathological grade can have effects on the gene expression properties of breast cancers. Luminal IHC type A is more common in breast cancer and is associated with better outcomes. However, age, histological type, familial history, and menopause status had no effects on the IHC properties of breast cancer.

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