Epidermal Growth Factor Receptor Negative Patients Research Articles

Comparison of Treatment Outcome in EGFR Positive and Negative Patients with Non Small Cell Lung Cancer: A Longitudinal Study

Introduction: Lung cancer is one of the most common malignancies to occur worldwide. Two main subtypes of lung cancer include small cell lung cancer and Non Small Cell Lung Cancer (NSCLC). Patients with advanced stage NSCLC who achieve good response with Tyrosine Kinase Inhibitors (TKI) have been found to have Epidermal Growth Factor Receptor (EGFR) mutation. The first biomarker identified for targeted treatment in lung cancer was EGFR and patients of NSCLC with EGFR mutation have superior survival outcome when treated with targeted therapy as compared to conventional chemotherapy. Aim: To compare the outcome of targeted therapy to mutation to EGFR and conventional therapy in non mutant lung cancer patient of NSCLC. Materials and Methods: The present longitudinal study was conducted in the Department of TB and Respiratory Diseases, Jawaharlal Nehru Medical College and Hospital, Aligarh, Uttar Pradesh, India from July 2017 to November 2019 on a sample size of 80. Patients diagnosed with NSCLC and EGFR mutation status were included in the study. They were started on TKI if tumour was EGFR positive and on conventional chemotherapy (cisplatin plus paclitaxel) if no mutation was detected on histopathology. Among the study group, 35 patients were EGFR positive and started on geftinib (group I), 45 were EGFR negative and received platinum-based chemotherapy (group II). Outcomes were measured in terms of progression-free survival, Overall Survival (OS), and toxicities. Statistical analysis of data was done using Statistical Package for the Social Sciences (SPSS) version 20.0. Results: Among the study group, 35 patients were EGFR positive and started on geftinib (Group I), 45 were EGFR negative and received platinum-based chemotherapy (group II). The mean age of EGFR positive patients was 58.91 years and for EGFR negative patients was 60.11 years. In group I, there was no complete response while 28.5% had partial response, 45.5% had stable disease and 25.7% had progressive disease. In group II, 15.5% patients had complete response, 33.3% had partial response,17.7% had stable disease and 33.3% had progressive disease. Mean progression-free survival in group I (5.65 months) was significantly higher than group II (4.26 months). The mean OS in group I (7.85 months) was slightly higher than group II (6.72 months). Both haematological and non haemaotlogical toxicities were significantly higher in group II. Conclusion: Patients with EGFR positive expression subjected to Gefitinib had significant mean progression-free survival with an acceptable range of non haematological toxicities and no haematological toxicities, as compared to the EGFR negative patients on conventional chemotherapy.

Stereotactic Body Radiation Therapy for Oligoprogressive Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> The role of stereotactic body radiation therapy (SBRT) in oligoprogressive non-small cell lung cancer (NSCLC) is controversial, given the current standard of care in this setting favors changing to the next-line of systemic therapy. To address this important knowledge gap, we hypothesized that SBRT in a subset of patients with oligoprogressive NSCLC offers durable response, omitting the need to change or escalate systemic therapy. We evaluated patients on systemic therapy for NSCLC treated at our institution who subsequently received SBRT in the oligoprogressive setting. <h3>Materials/Methods</h3> A retrospective analysis of NSCLC patients who underwent SBRT for oligoprogressive disease from 2017 to 2021 was performed. Variables included in the analysis were age, gender, presence of brain metastases, and number of metastatic sites treated at the time of progression. Lesions defined as progressing were based on the response evaluation criteria in solid tumors (RECIST v1.1); presence of brain metastases was not considered as a site of progression. Progression-free survival (PFS), our primary endpoint, was calculated using the Kaplan-Meier method and defined as the time from completion of SBRT to next progression or death, whichever occurred first. Subset analyses were performed on epidermal growth factor receptor (EGFR) positive patients receiving a tyrosine kinase inhibitor (TKI) and PD-L1 ≥50% vs <50%. Log-rank and Cox proportional hazards regression were used to evaluate predictors of PFS. <h3>Results</h3> A total of 105 patients were included; median age was 65 and 57% were female. The majority were adenocarcinoma (79%). Twenty-six percent of patients were EGFR positive and received a TKI. PD-L1 expression was <50% in 31%, ≥50% in 16% and unknown in 53% of patients. The number of oligoprogressive sites treated at the time of progression was 1-2 in 77% and 3-6 in 23% of patients. At a median follow up of 12 months (range, 1-60 months), median time to progression after completion of SBRT was 4 months (range, 1-37 months). Median PFS for the entire cohort was 5.5 months (95% confidence interval [CI], 2.9-8.0). Median PFS for patients undergoing SBRT to 1-2 vs 3-6 sites of disease was 5.9 months (95% CI, 3.9-7.9) and 3.4 months (95% CI, 1.9-4.8), respectively. Median PFS for EGFR positive patients on TKI was 8.1 months (95% CI, 4.0-12.2), compared to 5.6 months (2.4-8.9) for EGFR negative patients. Median PFS for PD-L1 <50% was 5.6 months (95% CI, 4.0-7.2) vs 6.6 months (95% CI, 0.71-12.5) for PD-L1 ≥50%. Forty-five (43%) patients underwent additional SBRT. No radiation related grade 3 or higher toxicities were reported. <h3>Conclusion</h3> SBRT is a safe and viable treatment option for oligoprogressive NSCLC. Our findings suggest EGFR positive patients and those with 1-2 sites of progression may benefit more. Future prospective studies are needed to validate these findings.

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma.

Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

P1.13-39 Epidermal Growth Factor Receptor Mutation Among Non-Small Cell Lung Cancer Patients in Trinidad and Tobago: Frequency and Trends

Almost 70% of non-small cell lung cancer (NSCLC) patients present with unresectable disease and may benefit from chemotherapy or biologic therapy. Mutation testing now plays a vital role in their diagnostic work-up to determine which patients are more likely to receive benefit from biologic therapies. The rate of epidermal growth factor receptor (EGFR) mutations varies significantly across geographic regions and ethnicities, ranging from 13% to 64% in some areas. Several subgroups such as females, East Asians, never-smokers and those with adenocarcinoma histology have the highest reported rates of EGFR mutations. Regionally, the French West Indies reports an EGFR mutation rate of 36%. The frequency of the EGFR mutation among NSCLC patients in Trinidad and Tobago has not been previously reported in the literature. An observational, retrospective study was done using data obtained from the Lung Malignancy Unit (LMU) based at the Eric Williams Medical Sciences Complex (EWMSC). The EWMSC is the sole referral centre in Trinidad and Tobago for lung cancer and the LMU is responsible for co-ordinating clinical and educational services regarding lung cancer nationwide.The study population was limited to primary NSCLC patients presenting to the EWMSC from January 2014 to June 2017 whose biopsy samples were sent for EGFR testing and received either a positive or negative result. Patients’ clinical data was entered onto a spreadsheet and analysed using Microsoft Excel. The data for 94 patients with NSCLC were analysed. 68 of these patients were male, while 58 admitted to a history of smoking. EGFR mutations were present in 39.4% of this study population. Females demonstrated a significantly higher EGFR mutation rate than males (73.1% vs 26.5%, p < 0.0001). Smoking status was found to be significantly associated with differences in EGFR mutation status (p < 0.01). The mean age of presentation was similar despite of EGFR mutation status. Although a larger number of EGFR positive patients compared to EGFR negative patients had adenocarcinoma histology (97.3% vs. 89.5%), this was not found to be statistically significant (p = 0.29). The frequency of EGFR mutations in this study population (39.4%) was higher than most regions of the world but similar to that reported in the French Antilles. Sex and smoking status were significantly associated with differences in EGFR mutation status.

Abstract P1-06-07: Clinical and molecular relevance of intra-tumor genetic heterogeneity in breast cancer: Integrative analysis of data from The Cancer Genome Atlas

Abstract Background: Intra-tumor heterogeneity (ITH) plays a pivotal role in driving breast cancer progression and therapeutic resistance. Emerging evidence has indicated that the extent of genetic heterogeneity may serve as a clinically useful biomarker. While several studies have suggested the prognostic value of ITH in several cancer types, the clinical significance of genetic ITH and molecular portraits that correlated with different ITH levels were poorly understood in breast cancer. The establishment of algorithms estimating genetic ITH based on sequencing of bulk tumor DNA offered us an opportunity to explore the clinical implication of ITH in large breast cancer cohorts and, for the first time, to use integrative genomic analyses to reveal molecular portraits related to intra-tumor genetic heterogeneity. Methods: We assessed 916 female breast cancer patients from The Cancer Genome Atlas. Mutant-allele tumor heterogeneity (MATH) values were calculated from whole-exome sequencing data. We used integers nearest to the tertiles of the MATH values as cutoff points to divide the patients into three groups nearly equal in size. The association between MATH value and clinical characteristics was evaluated, followed by survival analyses in these different MATH groups. We then compared the rates of total non-silent somatic mutations among the different MATH groups, and further determined the mutations independently associated with high MATH by logistic regression adjusting for T classification and clinical subtypes. Similar methods, superadding somatic copy number alteration (SCNA) burden in logistic model, were used to evaluate SCNA events that were significantly associated with high MATH level. Gene enrichment between the high and rest MATH groups was analyzed using Gene Set Enrichment Analysis. Results: The patients were divided into low (MATH value lower than 33), intermediate (MATH between 33 and 46) and high (MATH higher than 46) MATH groups. High T stage, African American race, and triple-negative or basal-like subtype were associated with a higher MATH level (all P&amp;lt;0.001). In hormone receptor-positive and human epidermal growth factor receptor-negative patients, the high MATH group showed a tendency toward a worse overall survival (P=0.052); however, while in triple-negative breast cancer, both high and low MATH indicated a worse outcome (P=0.032). Furthermore, the TP53 mutation rate increased as MATH was elevated (P&amp;lt;0.001), whereas CDH1 mutations were correlated with a lower level of MATH (P=0.002). Several focal and arm-level SCNA events were more common in the high MATH group, including Chr8q24 with only the MYC gene in the “peak” region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation. Conclusion: Our study extended the knowledge concerning the clinical role of ITH in breast cancer, especially the distinct pattern of prognostic values in different clinical subtypes, which may help promote the clinical utilization of genetic ITH. Our attempt at exploring the molecular features related to ITH might provide clues for the source and consequences of ITH, inspiring subsequent experiments investigating the laws underling tumor heterogeneity. Citation Format: Ma D, Jiang Y-Z, Liu X-Y, Liu Y-R, Yu K-D, Shao Z-M. Clinical and molecular relevance of intra-tumor genetic heterogeneity in breast cancer: Integrative analysis of data from The Cancer Genome Atlas [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-07.

Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer.

Intra-tumor heterogeneity (ITH) plays a pivotal role in driving breast cancer progression and therapeutic resistance. We used a mutant-allele tumor heterogeneity (MATH) algorithm to measure ITH and explored its correlation with clinical parameters and multi-omics data. We assessed 916 female breast cancer patients from The Cancer Genome Atlas. We calculated the MATH values from whole-exome sequencing data and further investigated their correlation with clinical characteristics, somatic mutations, somatic copy number alterations (SCNAs), and gene enrichment. The patients were divided into low, intermediate, and high MATH groups. High T stage, African American race, and triple-negative or basal-like subtype were associated with a higher MATH level (all P<0.001). In hormone receptor-positive and human epidermal growth factor receptor-negative patients, the high MATH group showed a tendency toward a worse overall survival (P=0.052); Furthermore, the TP53 mutation rate increased as MATH was elevated (P<0.001), whereas CDH1 mutations were correlated with a lower level of MATH (P=0.002). Several focal and arm-level SCNA events were more common in the high MATH group (P<0.05), including Chr8q24 with only the MYC gene in the "peak" region. Similarly, high MATH was associated with gene set enrichment related to the MYC pathway and proliferation. Our integrative analysis reveals the clinical and genetic relevance of ITH in breast cancer. These results also suggest the origin and natural history of clonal evolution and intra-tumor genetic heterogeneity, which warrant further investigation.

Prognostic significance and frequency of EGFR expression and amplification in surgically resected advanced gastric cancer.

The aim of this study is to find the frequency and the role of epidermal growth factor receptor expression as a prognostic biomarker in gastric cancer. We evaluated the prognostic value and frequency of epidermal growth factor receptor expression and amplification using immunohistochemistry and silver in situ hybridization in a large cohort of curatively resected gastric cancer. Of the total of 935 cases, 294 (31.4%), 101 (10.8%) and 36 (3.9%) patients showed epidermal growth factor receptor 1+, 2+ and 3+ expression on immunohistochemistry, respectively. Epidermal growth factor receptor-positive (2+/3+) patients more frequently had intestinal type than epidermal growth factor receptor-negative (0/1+) patients (82.5 vs. 44.1%, P < 0.001). After adjusting for sex, age, stage and adjuvant chemotherapy, epidermal growth factor receptor-positive patients had a favorable overall survival outcome compared with epidermal growth factor receptor-negative patients (hazard ratio, 0.734; 95% confidence interval, 0.541-0.997; P = 0.047), especially in Stage III disease (hazard ratio, 0.676; 95% confidence interval, 0.472-0.968; P = 0.033). Among the 393 cases available for in situ hybridization, the correlation between immunohistochemistry and in situ hybridization was statistically significant (P = 0.001). Thirteen patients with gene amplification (3.3%) did not show different survival outcome with others (P = 0.359). Epidermal growth factor receptor positivity was an independent favorable prognostic factor for gastric cancer, especially in Stage III disease.

Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations.

BackgroundPharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).Patients and methods.Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.ResultsFifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2–3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.ConclusionsWhile patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.

Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival.

BackgroundThe brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.Patients and methodsWe retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.ResultsOut of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.ConclusionsExcept for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.

Role of Epidermal Growth Factor Receptor (EGFR) and HER2-neu Receptor Expression in Predicting Biochemical Failure after Radical Radiotherapy for Prostate Cancer

CONCLUSION: •Patients with prostate cancer with overexpression of either or both EGFR and HER2 on IHC have an increased risk of biochemical relapse after radical radiotherapy. Alternative strategies of either surgery or utilization of EGFR and HER2 inhibition combined with radiotherapy need to be considered for such patients. :EGFR and HER2 expression was evaluated by immunohistochemistry (IHC) in 84 patients treated with radical radiotherapy in the Northern Centre for Cancer Treatment, in Newcastle in the UK between 1996 and 2000.

Nuclear EGFR in ductal invasive breast cancer: correlation with cyclin-D1 and prognosis

The epidermal growth factor receptor (EGFR)-family and cyclin-D1 have been extensively studied in breast cancer; however systematic studies that examine protein expression and gene status in the same cohort of patients are lacking. Also emerging evidences suggest existence of a direct EGFR-signaling pathway, which involves cellular transport of EGFR from cell membrane to the nucleus, and transcriptional regulation of the target genes. Thus, we examined the protein expression of membrane EGFR, nuclear EGFR, cyclin-D1 and the corresponding gene status in 113 breast carcinomas by immunohistochemistry and fluorescence in situ hybridization using tissue microarrays. Membrane EGFR overexpression and EGFR gene amplification were detected in 2% cases, while nuclear EGFR was detected in 40% of cases, with 12% having high nuclear EGFR staining. Nuclear EGFR correlated with tumor size (P=0.0005), lymph node metastasis (P=0.0288), Nottingham prognostic index (P=0.0011) and estrogen receptor (ER) expression (P=0.0258) but the letter correlation was observed only in premenopausal group of patients. Strong cyclin-D1 expression and cyclin-D1 gene (CCND1) amplification were found in 64 and 13% of the cases, respectively. Cyclin-D1 expression showed positive correlation with ER (P=0.0113) and inverse correlation with Nottingham prognostic index (P=0.0309) and membrane EGFR (P=0.0201). CCND1 amplification also showed inverse correlation with membrane EGFR (P=0.0420). A strong correlation between membrane EGFR expression and gene amplification (P=0.0035), as well as cyclin-D1 overexpression and gene amplification (P=0.0362), was demonstrated. On univariate analysis cyclin-D1 expression showed a correlation with longer overall survival in the premenopausal group and nuclear EGFR correlated with shorter overall survival in whole cohort as well in the premenopausal group of patients. Multivariate analysis revealed nuclear EGFR to be an independent prognostic factor and showed 3.4 times greater mortality risk for nuclear EGFR+++ patients as compared with nuclear EGFR negative patients (hazard ratio =3.402; P=0.0026).

Epidermal Growth Factor Receptor as a Predictor of Tumor Response to Preoperative Chemoradiation in Locally Advanced Gastric Carcinoma

The purpose of our study was a retrospective evaluation whether the intensity of epidermal growth factor receptor (EGFR) expression predicts tumor response to preoperative chemoradiotherapy in patients with locally advanced gastric carcinoma. Thirty-six patients with gastric adenocarcinoma (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45 Gy of gastric irradiation with continuous 5-fluorouracil and weekly cisplatin. Surgical resection was performed 4-6 weeks later. EGFR expression in pretreatment tumor biopsies was assessed by immunohistochemistry. Level of EGFR expression was determined from the intensity and extent of staining. Tumor response was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. Seventeen patients responded to preoperative chemoradiation -- 8 patients (22%) had pathologic complete response, 9 patients (25%) were downstaged. Positive EGFR expression was found in 8 tumors (22%), and represented a significant predictive marker of poor tumor response in multivariate logistic regression analysis (p = 0.015). Response to chemoradiotherapy was found in 60% (16/28) of EGFR negative patients and in 13% (1/8) of EGFR positive patients (p = 0.044). None of the eight EGFR positive patients achieved pathologic complete response in comparison with 8/28 (29%) of patients with EGFR negative staining (p = 0.16). EGFR may represent a molecular marker predictive for poor response to preoperative chemoradiotherapy in locally advanced gastric carcinoma.

Epidermal growth factor receptor (EGFR) immunohistochemistry: Comparison of antibodies (Abs) and cut points to predict benefit from gefitinib in a phase III placebo-controlled study in advanced non-small cell lung cancer (NSCLC)

7576 Background: Tumor tissues obtained from the ISEL phase III trial assessing the efficacy of gefitinib vs placebo in chemotherapy-pretreated NSCLC were used to evaluate two Abs (DAKO and Zymed) and assess whether different cut points of EGFR protein expression improved prediction of response and survival benefit from gefitinib. Methods: EGFR protein expression in tumor samples was assessed by immunohistochemistry using DAKO EGFR pharmDx kit (scoring percent of tumor cells with positive staining, predefined cut point of =10%) and Zymed monoclonal Ab clone 31G7 (scoring proportion of positive cells times staining intensity [scale 0–400], predefined cut point of =200). Results: Clinical characteristics of the patients (pts) assessed with DAKO (n=379) and Zymed (n=357) Abs reflected the overall study population (N=1692) with the exception of fewer never-smokers and Asians. Of the pts evaluated with DAKO/Zymed Abs, females represented 32%/31%; never-smokers, 13%/14%; Asians, 6%/4%; adenocarcinomas, 44%/42%; and 88%/88% of pts were refractory to most recent chemotherapy. With the above criteria, 70% of tumor samples were scored as positive using DAKO Ab and 68% using the Zymed Ab (agreement between assessments 76%). The objective response rates in gefitinib treated EGFR-positive pts defined with various cut points with DAKO Ab (=1% to =90%) varied between 8% and 12%, and with Zymed Ab (score =50 to =350), between 10% and 13%. Lower cut points with the DAKO Ab provided the best discrimination between EGFR positive and EGFR negative patients in terms of survival hazard ratios (HRs) comparing gefitinib to placebo, with a significant treatment/cut point interaction for the 10% cut point (p=0.049). A similar trend was noted for Zymed Ab, although the discrimination between HRs was less apparent and not significant for any cut point analyzed. Conclusion: Assessment with DAKO PharmDx kit, according to percentage of positive staining, may provide more accurate prediction of survival benefit for gefitinib-treated pts than assessment with Zymed Ab and staining index. Use of higher cut points to define positivity does not improve discrimination of the test. No significant financial relationships to disclose.

Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma.

Activation of the epidermal growth factor receptor (EGFR) has a role in oncogenesis and may correlate with prognosis. The aim of this study was to examine EGFR expression in esophageal adenocarcinoma and correlate EGFR status with pathologic and clinical prognostic features. An exploratory retrospective review of 38 patients with surgically resected esophageal adenocarcinoma was performed. All patients underwent an esophagogastrectomy with regional lymphadenectomy; 24 patients underwent primary resection and 14 patients had surgery after preoperative chemoradiation therapy. Immunohistochemical analysis was performed on paraffin-embedded tissue samples using an EGFR monoclonal antibody. Low- and moderate-grade tumors were positive for EGFR expression in 2 of 15 patients; poorly differentiated tumors were positive for EGFR expression in 13 of 23 patients (p=0.02). The median survival was 35 months (confidence interval [CI]: 29-40) for EGFR negative patients (n=23) and 16 months (CI: 10-22) for EGFR positive patients (n=13) (p=0.10). Disease recurred in 3 of 21 EGFR negative patients and 6 of 13 EGFR positive patients (p=0.06). Poorly differentiated adenocarcinomas of the esophagus demonstrated higher EGFR expression compared to low-grade tumors based upon immunohistochemical analysis. A trend toward improved disease-free and overall survival was seen in EGFR negative patients.

Epidermal growth factor receptor expression as a prognostic indicator in breast cancer

The significance of epidermal growth factor receptor (EGFR) status as a prognostic indicator was investigated by a competitive binding assay in 135 primary breast cancer patients. 55 patients (41%) were EGFR positive and EGFR status was negatively correlated with oestrogen receptor (ER) status ( P < 0.01). 5-year postoperative follow-up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients ( P < 0.05). There was no difference between the two groups in tumour size, axillary node involvement, age and menopausal status. Analysis by axillary node status demonstrated the poor prognosis of the EGFR positive group in node positive patients. As yet, no difference in prognosis has been seen in node negative patients. A higher frequency of haematopoietic relapse was observed in EGFR positive patients. Simultaneous or sequential EGFR measurements in primary tumour and metastatic sites of 34 patients showed that expression of EGFR was more enhanced in metastatic sites.