Use of microarray analysis of differentially expressed genes in luminal B subtype of breast cancers to evaluate NHERF1 as a marker of endocrine resistance

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11015-11015
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
E. Ruckhaeberle ◽  
L. Hanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Biology ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

11015 Background: In vitro and in vivo data demonstrate that the expression of estrogen receptor (ER) in breast cancer is mainly associated with low proliferation. Gene expression profiling has recently been used to identify a group of high proliferating estrogen receptor positive breast cancers (the luminal B subtype), which are associated with a prognosis that is even worse than that of high proliferating estrogen receptor negative tumors. The analysis of those tumors might provide valuable information about breast cancer biology and could be helpful for adjuvant or neoadjuvant treatment decisions.Methods and Results: We analyzed microarray data from breast cancer specimens to gain insight into genes which play a role in estrogen receptor signalling. Genes were identified showing strong expression in high proliferating ER-positive tumors but no expression in either Ki67-/ER+ or Ki67+/ER- samples. Among these genes the Na+/H+ exchanger regulatory factor NHERF1 was found. We assessed the clinical relevance of NHERF1 transcript levels using a total of 2469 breast cancers. Analysis indicates that enhanced NHERF1 expression is associated with metastatic progression and poor prognosis of breast cancer patients. We found no correlation between NHERF1 and the nodal status as well as age, but positive correlations for tumor size (P<0.001), grade (P<0.001) and erbb2 (P=0.033). Weak NHERF1 expression correlated with longer disease free survival (DFS) in grade 1 and 2 tumors, but not in grade 3 breast cancers. Since NHERF1 expression is strongly linked to the presence of ER, the predictive value for endocrine treatment was analyzed. For samples with weak or none NHERF1 expression a treatment benefit was observed (P=0.007). While untreated patients display a 10 yr DFS rate of 67.2 ± 3.8%, endocrine treatment resulted in 80.1 ± 4.0%. In contrast no differences in disease free survival were found for corresponding NHERF1 expressing breast cancers. Conclusions: Our data indicate that expression of NHERF1 defines a state of differentiation, where breast cancer cells are refractory to endocrine treatment. No significant financial relationships to disclose.

Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects.

1989 ◽  
Vol 7 (6) ◽  
pp. 803-815 ◽  
Author(s):  
R R Love
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Primary Breast Cancer ◽  
Cancer Biology ◽  
Biological Effects ◽  
Disease Free Survival ◽  
Free Survival ◽  
Beneficial Effects ◽  
Tamoxifen Citrate ◽  
Disease Free

Since its introduction into clinical use in the early 1970s, the synthetic antiestrogen tamoxifen citrate has been shown to contribute to the control of human breast cancer in increasingly significant ways. While its mechanisms of action and pharmacology are incompletely understood, tamoxifen appears to act predominantly by blocking the action of estrogen by binding to the estrogen receptor. Clinical trials of tamoxifen for 1 to 2 years in primary breast cancer demonstrate consistent beneficial effects on disease-free survival, but only suggested beneficial effects on survival. Routine use of adjuvant tamoxifen for 5 years or more will depend on the results of ongoing large clinical trials of efficacy and detailed studies of unknown biological effects on other tissues.

Disease-free survival pattern in breast cancer patients in India treated in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12030-e12030 ◽  
Author(s):  
Basavalinga S. Ajaikumar ◽  
Kodaganur Srinivasachar Gopinath ◽  
B S Srinath ◽  
Ramesh Bilimagga S ◽  
Nalini K Rao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Distant Failure ◽  
Her 2 ◽  
Disease Free

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.

scholarly journals Testing for HER2 in Breast Cancer: A Continuing Evolution

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Sejal Shah ◽  
Beiyun Chen
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Humanized Monoclonal Antibody ◽  
Epidermal Growth ◽  
Invasive Breast Carcinomas ◽  
Disease Free

Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.

Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer

2003 ◽  
Vol 21 (6) ◽  
pp. 976-983 ◽  
Author(s):  
I. Craig Henderson ◽  
Donald A. Berry ◽  
George D. Demetri ◽  
Constance T. Cirrincione ◽  
Lori J. Goldstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Confidence Interval ◽  
Chemotherapy Regimen ◽  
Disease Free Survival ◽  
Free Survival ◽  
Adjuvant Chemotherapy Regimen ◽  
Disease Free

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

Aromatase Inhibitors in Breast Cancer: An Update

2002 ◽  
Vol 9 (6) ◽  
pp. 490-498 ◽  
Author(s):  
Diana E. Lake ◽  
Clifford Hudis
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Metastatic Disease ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Management Approach ◽  
Free Survival ◽  
Early Results ◽  
Disease Free

Background Tamoxifen has been the endocrine treatment of choice for patients with breast cancer. The development of selective aromatase inhibitors has offered an alternative management approach for patients in whom a hormonal approach is indicated. Methods The authors reviewed reports in which aromatase inhibitors were compared with tamoxifen for the treatment of metastatic disease, as well as information pertinent to their use as adjuvant therapy. Results Both nonsteroidal (anastrozole and letrozole) and steroidal (exemestane) aromatase inhibitors for metastatic disease appear to provide superior efficacy and a better toxicity profile in first- and second-line treatment of metastatic disease than tamoxifen. Early results from the ATAC trial suggest anastrozole is superior to tamoxifen for disease-free survival, particularly in receptor-positive patients, and in reducing the incidence of contralateral breast cancer. Conclusions Aromatase inhibitors have important roles in optimal management of postmenopausal patients with hormone-responsive metastases in both the adjuvant and advanced-disease settings.

scholarly journals SIGNIFICANCE OF IODINE SYMPORTER FOR PROGNOSIS OF THE DISEASE COURSE AND EFFICACY OF NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH BREAST CANCER OF LUMINAL AND BASAL SUBTYPES

2017 ◽  
Vol 39 (1) ◽  
pp. 65-68 ◽  
Author(s):  
V F Chekhun ◽  
A V Andriiv ◽  
N Yu Lukianova
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Predictive Marker ◽  
Paraffin Sections ◽  
Objective Criterion ◽  
Free Survival ◽  
Luminal B ◽  
Oncology Center ◽  
Disease Free

The aim of the research was to study the relation between expression of Na+/I- symporter (NIS) in breast cancer (BC) of different molecular subtypes and sensitivity of BC cells to neoadjuvant chemotherapy (NACT) and to assess whether NIS expression may be used as a predictive marker of treatment efficacy. Materials and Methods: The study included 148 women with BC of stage II–III who were treated at the Precarpathian Clinical Oncology Center during 2012–2017. All patients were treated with NACT that included 2–6 cycles of chemotherapy by FAC, AC scheme with 21 day intervals. NACT efficacy was evaluated every 2 cycles by mammography according to RECIST criteria. Morphological and immunohistochemical study of NIS expression was performed by the standard methods on paraffin sections of surgically resected tumors. Results: The heterogeneity of different molecular BC subtypes regarding response to the NACT has been found. Her2/neu-positive and basal BC subtypes were the least susceptible to the NACT (p < 0.05). It was shown that NIS expression is related to the sensitivity of luminal B and basal BC subtypes to the NACT. The highest expression of NIS and impairment of its functional activity was registered in the group of patients with tumors resistant to NACT (stabilization of the disease or its progression) of luminal B (220 ± 8.6 points) and basal subtypes (290 ± 11.3 points) (p < 0.05). It was revealed that the disease-free survival of patients with BC of luminal B and basal subtypes was higher in the absence of NIS expression in tumor cells (p < 0.05). Conclusions: The results indicate that NIS can be used as an objective criterion for predicting the sensitivity of luminal B and basal BC subtypes to NACT, which will provide improved treatment outcomes in this group of patients.

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