Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.

1993 ◽  
Vol 11 (10) ◽  
pp. 1936-1942 ◽  
Author(s):  
R Seshadri ◽  
F A Firgaira ◽  
D J Horsfall ◽  
K McCaul ◽  
V Setlur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Tumor Size ◽  
Copy Number ◽  
Node Negative ◽  
Node Positive ◽  
Oncogene Amplification ◽  
Her 2 ◽  
Neu Oncogene

PURPOSE To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients. METHODS HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained. RESULTS HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size. CONCLUSION Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients.

HER-2/neu oncogene protein and prognosis in breast cancer.

1989 ◽  
Vol 7 (8) ◽  
pp. 1120-1128 ◽  
Author(s):  
A K Tandon ◽  
G M Clark ◽  
G C Chamness ◽  
A Ullrich ◽  
W L McGuire
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Node Negative ◽  
Node Positive ◽  
Her 2 ◽  
Neu Oncogene ◽  
Disease Free ◽  
Oncogene Protein ◽  
Positive Breast Cancer

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.

Effects of different chemotherapy regimens and tamoxifen for HER2 over-expressed breast cancer adjuvant therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11048-11048
Author(s):  
J. Zhang ◽  
Y. Liu ◽  
X. Hao ◽  
Z. Fang ◽  
L. Ning
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Subgroup Analysis ◽  
Negative Group ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Over Expression ◽  
Node Positive ◽  
Her 2

11048 Background: To evaluate effects of different adjuvant chemotherapy regimens and TAM in HER-2-overexpressed breast cancer patients. Methods: To study 1625 primary breast cancer cases after operation from 2002.7 to 2005.11 given adjuvant chemotherapy ,600 cases given CMF, 600 cases given CEF, and 425 cases given T-regimen (anthracyclines follow taxanes),1090 HR+ cases given tamoxifen. HER-2 expression were measured by immunohistochemistry (IHC). Median follow-up time is 42 months. Results: (1)3yr DFS of HER-2 over-expression is inferior to HER-2 negative ones in CMF group(p<0.05), no difference between HER-2- overexpressed and HER-2-negative group treated with either CEF or taxanes-based regimen (p>0.05). Subgroup analysis suggested: patients treated with CMF, 3yr DFS of HER-2 over-expression is inferior to HER-2-negative ones in node-positive subgroup, but no difference in node-negative ones; HER-2 expression has no influence on effects of CEF or T-regimen in node-positive or node-negative subgroup. (2) 425 HER-2 over-expressed patients(183 cases given CMF , 121 cases given CEF , and 121 cases given T-regimen): compared to CMF, anthracyclines and taxanes are more effective, but no difference between anthracyclines and T-regimen. (3) 235 patients with HER-2 over- expression and node-postive (72 cases given CMF , 68 cases given CEF, and 95 cases given T-regimen):, anthracyclines and taxanes are more effective than CMF, but no difference between anthracyclines and T-regimen. (4)3yr DFS is 91.23% in HER-2 over-expressed group and 93.42% in HER-2-negative group (p=0.04) with TAM. HER-2 over-expressed patients are resistant to TAM. (5) Subgroup analysis suggested that: 3yr DFS is 88.67% with HER-2 over-expression and 92.20% with HER-2-negative in postmenopausal node-positive subgroup(p=0.0069), postmenopausal patients with HER-2 over-expression and node-positve are resistant to TAM; no difference in either premenopausal or postmenopausal node-negative subgroup (p>0.05). Conclusions: No difference between Anthracyclines based and T-regimens for HER2 over-expressed patients with node-positive for 3yr DFS.Postmenopausal ER+/PR+ patients with HER2 over- expression are resistant to Tamoxifen endocrine therapy. No significant financial relationships to disclose.

scholarly journals A retrospective FISH study of HER-2/neu oncogene amplification in relapsed and non-relapsed node-negative breast cancer

1999 ◽  
Vol 1 (2) ◽  
pp. 47-47
Author(s):  
H F L Mark ◽  
B Aswad ◽  
W Taylor ◽  
M Samy ◽  
C-L Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Node Negative ◽  
Oncogene Amplification ◽  
Node Negative Breast Cancer ◽  
Her 2 ◽  
Neu Oncogene

Comparison of HER-2/ neu Oncogene Amplification Detected by Fluorescence In Situ Hybridization in Lobular and Ductal Breast Cancer

2002 ◽  
Vol 10 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Seth I. Rosenthal ◽  
Peter L. Depowski ◽  
Christine E. Sheehan ◽  
Jeffrey S. Ross
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Oncogene Amplification ◽  
Ductal Breast Cancer ◽  
Her 2 ◽  
Neu Oncogene

Cured of breast cancer?

1995 ◽  
Vol 13 (1) ◽  
pp. 62-69 ◽  
Author(s):  
H Joensuu ◽  
S Toikkanen
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Survival Rates ◽  
Locoregional Therapy ◽  
Short Term ◽  
Node Negative ◽  
Node Positive ◽  
Node Positive Disease ◽  
Histologic Types

PURPOSE That patients can be ultimately cured of breast cancer has been questioned, because late deaths from the disease have been observed even several decades after the diagnosis. The purpose of this study was to investigate late mortality caused by breast cancer. PATIENTS AND METHODS Using the files of local hospitals and the Finnish Cancer Registry, we identified all patients with histologically diagnosed invasive breast cancer in a defined urban area (city of Turku, Finland) from 1945 to 1969 (n = 601). In 563 cases (94%), clinical data and histologic and autopsy slides could be reviewed, and these women had been monitored for a median of 29 years (range, 22 to 44; n = 66) or until death (n = 497). RESULTS Mortality from breast cancer was observed even during the fourth follow-up decade, but if women who were diagnosed with contralateral breast cancer were excluded (n = 30), no deaths from breast cancer were identified after the 27th year of follow-up evaluation. The 30-year survival rates were 62% (95% confidence interval [CI], 54% to 70%), 19% (95% CI, 13% to 25%), and 0% for women with pN0 (node-negative) and pN1 or pN2 (node-positive) disease, respectively. High 30-year survival rates were found in small (pT1N0M0) unilateral cancers (80% alive; 95% CI, 66 to 94%), and in the lobular (45% alive; 95% CI, 31% to 59%) and the special histologic types (81% alive; 95% CI, 67% to 95%). These survival rates were obtained when correcting either for known intercurrent deaths or for mortality in the age- and sex-matched general population. CONCLUSION Breast cancer, node-negative and node-positive, may be permanently cured even if treated with locoregional therapy only. The survival figures listed here may be considered as minimum values, because women with breast cancer diagnosed in the same area from 1970 to 1984 showed significantly improved short-term (< 20 years) survival rates over those diagnosed from 1945 to 1969.

Pepsinogen C is a new prognostic marker in primary breast cancer.

1995 ◽  
Vol 13 (1) ◽  
pp. 54-61 ◽  
Author(s):  
F Vizoso ◽  
L M Sánchez ◽  
I Díez-Itza ◽  
A M Merino ◽  
C López-Otín
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Survival Duration ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Pepsinogen C ◽  
Node Positive

PURPOSE Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas. PATIENTS AND METHODS Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months. RESULTS A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated (grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). CONCLUSION Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.

Sentinel node biopsy after neoadjuvant treatment in breast cancer: Five-year follow-up of patients with clinically node-negative or node-positive disease before treatment

2016 ◽  
Vol 42 (3) ◽  
pp. 361-368 ◽  
Author(s):  
V. Galimberti ◽  
S.K. Ribeiro Fontana ◽  
P. Maisonneuve ◽  
F. Steccanella ◽  
A.R. Vento ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sentinel Node ◽  
Sentinel Node Biopsy ◽  
Neoadjuvant Treatment ◽  
Node Negative ◽  
Node Positive ◽  
Node Biopsy ◽  
Node Positive Disease

scholarly journals Internal Mammary Node Irradiation in Node-Positive Breast Cancer Treated with Mastectomy and Taxane-Based Chemotherapy

2021 ◽  
Author(s):  
Won Kyung Cho ◽  
Jee Suk Chang ◽  
Seung Gyu Park ◽  
Nalee Kim ◽  
Doo Ho Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Locoregional Recurrence ◽  
Disease Free Survival ◽  
Internal Mammary Node ◽  
Free Survival ◽  
Node Positive ◽  
Internal Mammary ◽  
Positive Breast Cancer

Abstract Purpose: It is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.Methods and Materials: We analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received adjuvant radiotherapy with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.Results: After a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220-0.962). In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; p = 0.021) and OS (HR 0.233, p = 0.018).Conclusions: IMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy radiation therapy, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

BCIRG 006: Docetaxel and trastuzumab-based regimens improve DFS and OS over AC-T in node positive and high risk node negative HER2 positive early breast cancer patients: Quality of life (QOL) at 36 months follow-up

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19647-19647 ◽  
Author(s):  
N. J. Robert ◽  
W. Eiermann ◽  
T. Pienkowski ◽  
J. Crown ◽  
M. Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Relative Reduction ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Negative ◽  
Risk Of Death ◽  
Node Positive

19647 Background: The primary objective of the BCIRG 006 trial was to determine if the use of trastuzumab in early high-risk HER2-positive breast cancer significantly improved clinical outcomes. A secondary objective was to evaluate the QOL of patients receiving the 2 treatments. Methods: The BCIRG 006 trial compared adjuvant standard AC (doxorubicin/cyclophosphamide x 4 cycles) followed by docetaxel x 4 [AC-T] or 2 trastuzumab-containing regimens, AC followed by T with trastuzumab x 1 year [AC-TH] or TCarbo x 6 with trastuzumab x 1 year [TCH] in patients with node positive or high-risk node negative HER2-positive early breast cancer (n=3222). Results: The 2nd planned interim analysis, median follow-up at 36 months, showed that both AC-TH and TCH significantly improved the DFS and OS over the control (relative reduction risk of relapse 39% (P<0.0001) and 33% (P=0.0003) respectively, for AC-TH and TCH vs control). Relative reduction in the risk of death was 41% (P=0.0041) and 34% (P =0.017) respectively, for AC-TH and TCH vs control. Congestive heart failure occurred in 0.4% of patients in AC-T and TCH vs 1.9% of patients in AC-TH. Global safety profile was acceptable in all 3 arms and more favourable in TCH than AC-TH. QOL, a secondary endpoint of this trial, was assessed using the EORTC QLQC-30, BR-23, and EQ5D. We will present the primary QOL endpoints comparing Physical Function, Global Health Status, Future Perspectives, and Systemic Treatment Effects change scores from baseline to mid-chemotherapy, end of chemotherapy, and 12 months follow-up (with a 10% change considered clinically important). The proportion of patients with improved/stable/worsened QOL scores will be compared with chi-square tests. Other QOL exploratory analyses will be presented. [Table: see text]

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