A Clinical and Biological Comparison Between Malignant Mixed Müllerian Tumors and Grade 3 Endometrioid Endometrial Carcinomas

2009 ◽  
Vol 19 (2) ◽  
pp. 261-265 ◽  
Author(s):  
Amy E. Bland ◽  
Rebecca Stone ◽  
Cara Heuser ◽  
Jianfen Shu ◽  
Amir Jazaeri ◽  
...  
Keyword(s):  
Uterine Cancer ◽  
Growth Factor Receptor ◽  
Myometrial Invasion ◽  
Clinicopathologic Features ◽  
Tissue Samples ◽  
Free Interval ◽  
Egfr Expression ◽  
Phosphorylated Akt ◽  
Her 2 ◽  
Grade 3

Objective:To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested.Methods:One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification.Results:Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC.Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples.Conclusions:Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies.

Pharmacodynamic Studies of Gefitinib in Tumor Biopsy Specimens From Patients With Advanced Gastric Carcinoma

2006 ◽  
Vol 24 (26) ◽  
pp. 4309-4316 ◽  
Author(s):  
Federico Rojo ◽  
Josep Tabernero ◽  
Joan Albanell ◽  
Eric Van Cutsem ◽  
Atsushi Ohtsu ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Kinase Inhibitor ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Mitogen Activated Protein Kinase ◽  
Tumor Biopsy ◽  
Advanced Gastric Carcinoma ◽  
Egfr Expression ◽  
Phosphorylated Akt

Purpose Epidermal growth factor receptor (EGFR) is highly expressed in some gastric cancers and is implicated in cancer cell growth and proliferation. The objective of this study was to assess the in situ biologic activity of the EGFR tyrosine kinase inhibitor gefitinib in gastric tumor samples in a phase II study. Methods Patients with previously treated stage IV adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive gefitinib (250 or 500 mg/d). Tumor biopsies, obtained at screening and on day 28 of treatment, were assessed for biomarker expression using immunohistochemistry and analysis of apoptosis. Results One hundred sixteen tumor samples from 70 patients were available, 70 were baseline and 46 were on-therapy biopsies. At baseline, levels of EGFR expression significantly correlated with levels of phosphorylated EGFR (pEGFR; P < .001) and Ki67 expression (P = .011), but not with phosphorylated mitogen-activated protein kinase (pMAPK). After gefitinib treatment, levels of pEGFR in tumor cells were significantly reduced (P = .001); this was not the case for pMAPK and phosphorylated Akt (pAkt). However, in some cases gefitinib inhibited pAkt and these tumors had enhanced apoptosis. Likewise, there was a significant correlation between increased exposure to geftinib and enhanced apoptosis. Conclusion Gefitinib reached the tumors at concentrations sufficient to inhibit EGFR activation in advanced gastric carcinoma patients, although this did not translate into clinical benefit. Overall, intratumoral phosphorylation of MAPK and Akt was not significantly inhibited by gefitinib. However, the finding that decreases in pAkt correlated with enhanced apoptosis deserves further exploration.

Histological features and prognosis of patients with mucoepidermoid carcinoma of the parotid gland

1998 ◽  
Vol 112 (10) ◽  
pp. 944-947 ◽  
Author(s):  
Masashi Suzuki ◽  
Issei Ichimiya ◽  
Futoshi Matsushita ◽  
Goro Mogi
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Parotid Gland ◽  
Surgical Resection ◽  
Mucoepidermoid Carcinoma ◽  
Histological Features ◽  
Lower Survival Rate ◽  
Free Interval ◽  
Her 2 ◽  
Grade 3

AbstractHistological features and prognosis of patients with mucoepidermoid carcinoma of the parotid gland were analysed. Tumours from 13 patients were classified according to histological grades and immunoreactivity for HEK-2/neu. Surgical resection of the tumour was performed for all patients, and the overall five-year survival rate was 69 per cent. The patients whose histological grades were 1 or 2 showed a 100 per cent five-year survival rate, but no patient with grade 3 survived five years. Also, patients who had tumours that overexpressed HER-2/new had a lower survival rate (25 per cent) than patients with tumours that had weaker immunostaining (89 per cent). We considered tumours classified as grade 3 plus strong HER-2/neu expression to be ‘high malignancy’, and compared them with ‘low malignancy’ tumours that were grade 1 or 2 and had weaker HER-2/new staining. Patients with high malignancy tumours had shorter recurrence-free intervals and shorter overall survival than patients with low malignancy tumours. The overall survival period of the low malignancy cases was much longer than the recurrence-free interval; unlike that in the high malignancy tumour patients. These results suggest that the combination of histological grades and expression of HER-2/neu may be a useful predictor of the prognosis for mucoepidermoid carcinomata.

IFCT0401-bio trial: Pathological and EGF-r molecular analysis of tumor-biopsy samples from patients with non-resectable, pneumonic-type adenocarcinoma (P-ADC) treated by gefinitib. Preliminary results from surgical specimens

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7185-7185
Author(s):  
J. Cadranel ◽  
M. Wislez ◽  
F. Coulet ◽  
V. Poulot ◽  
J. F. Morã ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Bronchioloalveolar Carcinoma ◽  
Tumor Biopsy ◽  
Tissue Samples ◽  
Egfr Expression ◽  
Phosphorylated Akt ◽  
Pathological Review ◽  
Exon 19 Deletion ◽  
Exon 1 ◽  
Histologic Types

7185 Background: P-ADC is often a bronchioloalveolar carcinoma (BAC) variant in the 2004 WHO pathological classification. A French prospective multicentric phase II trial (IFCT0401) evaluated gefitinib as first line treatment in non-resectable P-ADC. Tissue samples were collected for central pathological review and molecular analysis in attempt to determine if an association existed between disease control (DC) by gefitinib and biological markers. Methods: Histologic types were classified according to the 2004 WHO classification as BAC variants and ADC, other types and as non-mucinous or mucinous/mixed. Immunohistochemistry were performed using antibodies against the following proteins: TTF1, Ki67, phosphorylated AKT, erbB2, and EGFR. Polysomy/amplification was examined for erbB2 and EGFR. EGFR 18–21 and K-ras 1 exons were amplified and sequenced. Results: A tissue specimen was collected from 67 of the 88 eligible participants, among which 35 were from surgical resection. This subgroup did not differ from the overall trial population in terms of sex ratio (0.51 vs 0.56), proportion of non-smokers (34 vs 55%) and DC rate (34 vs 29%). Results described herein were obtained in 22 of the 35 surgical specimens collected. Sixteen were BAC variants (73%) and 6 ADC other types. Of the 22, 14 were non-mucinous and 8 mucinous. TTF1, Ki67, P-AKT, erbB2 as well as EGFR expression did not differ between BAC variants and ADC other types. TTF1 and EGFR scores of expression were higher in non-mucinous than in mucinous P-ADC. DC on gefitinib was significantly associated with non-mucinous subtype (p = 0.006), higher TTF1 (p = 0.06) and EGFR (p = 0.07) scores of expression, but not with other markers. K-ras exon-1 codon 12 mutation was found in 6 tumors of which 5 progressed on gefitinib. Polysomy of EGFR was seen in 2 tumors, 1 of which also contained EGFR mutation (exon-19 deletion); both were controlled by gefitinib. Conclusions: Among patients with P-ADC who received gefitinib, non-mucinous subtype, high TTF1 or EGFR score of expression, and EGFR polysomy and/or mutation may have improved DC, while K-ras mutation seems associated with disease progression. [Table: see text]

EGFR expression in invasive anal carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 412-412 ◽  
Author(s):  
A. A. Paliga ◽  
R. Onerheim ◽  
A. Gologan ◽  
A. Spatz ◽  
T. Vuong
Keyword(s):  
Head And Neck ◽  
Anal Cancer ◽  
Squamous Cell ◽  
Anal Carcinoma ◽  
Growth Factor Receptor ◽  
Staining Intensity ◽  
Hpv Infection ◽  
Epithelial Tumor ◽  
Tissue Samples ◽  
Egfr Expression

412 Background: Squamous cell anal carcinoma (SCAC) treatment remains unchanged since the institution of chemoradiation over 4 decades ago. Epidermal growth factor receptor (EGFR) is a protein often expressed in aggressive cancers and that is the target of the monoclonal antibody: cetuximab. Concurrent cetuximab and radiation has been particularly effective treating squamous cell carcinoma of the head and neck. Like head and neck cancer, anal cancer is an epithelial tumor of the alimentary tract that is radioresponsive and is associated with HPV infection. The rarity of this cancer limits its evaluation for biological markers. This study set out to thoroughly characterize EGFR expression by immunohistochemistry in 101 invasive SCAC tissue samples. Methods: One hundred and one pretreatment paraffin embedded invasive SCAC biopsies, obtained from the Montreal area between 1999 and 2009, were tested for EGFR expression by immunohistochemistry. All samples were confirmed to harbor invasive anal carcinoma on H&E slide preparations. Corresponding cancerous areas were identified on paraffin tissue blocks and cut out for tissue microarray analysis. Samples were immunostained with an EGFR antibody (clone SPM 341) on the Discovery XT Autostainer (Ventana), and staining was assessed by light microscopy by two pathologists. A semiquantitative combination score combining staining intensity with the percent of cells staining gave a final score: just detectable or weak (1+); moderate (2+); strong/intense (3+). Results: Of 101 patient biopsies, 82 samples had sufficient material for interpretation. Of these samples, 72/82 (90%) stained positive for EGFR, while 41/82 (50%) samples displayed at least moderate to strong staining. Conclusions: This is the largest cohort of SCAC tissue samples tested to date for EGFR expression and it confirms that the vast majority of invasive SCAC overexpress EGFR. EGFR likely plays a role in anal cancer tumor-genesis and progression. Testing of EGFR inhibitors in this patient population is justified. No significant financial relationships to disclose.

Expression of HER-2/neu, epidermal growth factor receptor, vascular endothelial growth factor, cyclooxygenase-2, estrogen receptor, and progesterone receptor in small cell and large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathologic and prognostic study

2005 ◽  
Vol 15 (4) ◽  
pp. 646-656 ◽  
Author(s):  
S. Tangjitgamol ◽  
P. T. Ramirez ◽  
C. C. Sun ◽  
H. T. See ◽  
A. Jhingran ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Small Cell ◽  
Vascular Endothelial ◽  
Egfr Expression ◽  
Her 2 ◽  
Epidermal Growth ◽  
Cox 2 ◽  
Endothelial Growth Factor

We studied the immunohistochemical expression of HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor (ER), and progesterone receptor (PR) in uterine cervical small cell and large cell neuroendocrine carcinomas (SCNECs and LCNECs) from 24 patients seen at The University of Texas M.D. Anderson Cancer Center. The objectives were to determine their expression and prognostic role in survival. Twenty-three cases (95.8%) expressed VEGF. The tumors expressing EGFR, HER-2/neu, and COX-2 were modest in numbers: eight (33.3%), 10 (41.7%), and seven (29.2%), respectively. Only one tumor (4.2%) expressed ER, and only two tumors (8.3%) expressed PR. No significant differences in the expression of these factors were found between SCNECs and LCNECs or between stage I and stage II–III tumors. The median overall survival was 21.1 months (95% confidence interval [CI], 17.2–25.0 months). Only HER-2/neu expression was significantly associated with survival. Patients with negative HER-2/neu expression tumors had significantly shorter survival than those whose tumors were positive, 14.2 months (95% CI, 10.6−17.7 months) versus 33.1 months (95% CI, 0−76.92 months) (P = 0.03). There was a trend toward worse survival in patients with EGFR expression, but this finding was not significant. The combination of negative HER-2/neu expression and positive EGFR expression had the worst impact on survival.

The impact of lymphadenectomy in women with endometrioid uterine cancer: A study of 39,396 women

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5000-5000
Author(s):  
N. Karnik Lee ◽  
H. Wu ◽  
M. K. Cheung ◽  
K. Osann ◽  
A. Husain ◽  
...  
Keyword(s):  
African American ◽  
Uterine Cancer ◽  
Myometrial Invasion ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Stage Ii ◽  
Surgical Staging ◽  
Uterine Cancers ◽  
Grade 3 ◽  
The Impact

5000 Background: To determine the potential benefit of lymphadenectomy (LNX) during surgical staging procedure in women with early and advanced endometrioid uterine cancers. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results program from 1988 to 2001. Data were analyzed by using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of 39,396 women (median age: 65; range 19–102) with endometrioid uterine cancers, 12,333 (31.3%) underwent a surgical staging procedure with LNX. The remainder received a hysterectomy and bilateral salpingo-oophorectomy only. 34,871 (88.5%) were Caucasian, 1,742 (4.4%) were African-American, 1,841 (4.7%) were Asian and 942 (2.4%) were other. The 5-year disease-specific survivals (DSS) were 93.3%, 85.4%, 69.3%, and 38.3% in patients with FIGO stage I-IV diseases, respectively. The 5-year DSS of stage I-IV women who underwent LNX were 95.5%, 90.4%, 73.0%, and 53.3% compared to 96.6%, 82.3%, 61.2%, and 28.2% in those without LNX. Those with stage II (p < 0.001), III (p < 0.001), and IV (p < 0.001) diseases after LNX had significantly better survival; however, the benefit of LNX was not demonstrated in stage I disease. The proportion of stage I patients with grade I histology or tumors limited to the endometrium was significantly higher in those who did not receive LNX compared to those who did (54.8% vs. 34.7%; p < 0.001 for grade I disease; 26.6% vs. 15.9%; p < 0.001 for non-myometrial invasion). In stage I grade 3 endometrioid uterine cancer, patients with LNX had a better 5-year DSS than those without LNX (90.0% vs. 84.97%; p = 0.0001); however, these findings were not seen in grade I (p = 0.26) and grade II (p = 0.14) diseases. In the subset of patients with stage IC grade 3 disease, there was a trend toward an improvement in survival associated with LNX (81.7% vs. 76.5%; p = 0.07). In the overall study group, younger age, African-American race, advanced stage disease, grade 3 histology, and lymphadenectomy. Conclusions: Our data suggest that lymphadenectomy improves the survival of women with stage I grade 3, stage II-IV endometrioid uterine cancers. No significant financial relationships to disclose.

Trastuzumab, Paclitaxel, Carboplatin, and Gemcitabine in Advanced Human Epidermal Growth Factor Receptor-2/neu–Positive Urothelial Carcinoma: Results of a Multicenter Phase II National Cancer Institute Trial

2007 ◽  
Vol 25 (16) ◽  
pp. 2218-2224 ◽  
Author(s):  
Maha H.A. Hussain ◽  
Gary R. MacVicar ◽  
Daniel P. Petrylak ◽  
Rodney L. Dunn ◽  
Ulka Vaishampayan ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Urothelial Carcinoma ◽  
Growth Factor Receptor ◽  
Human Epidermal Growth Factor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Purpose We investigated the safety and efficacy (response rates, time to disease progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel in advanced urothelial carcinoma patients and prospectively evaluated human epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. Patients and Methods Advanced urothelial carcinoma patients were screened for Her-2/neu overexpression. Eligibility for therapy required human epidermal growth factor receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene amplification and/or elevated serum Her-2/neu, no prior chemotherapy for metastasis, and adequate organ function including a normal cardiac function. Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The primary end point was cardiac toxicity. Results Fifty-seven (52.3%) of 109 registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her-2/neu–positive patients had more metastatic sites and visceral metastasis than did Her-2/neu negative patients. Forty-four of 57 Her-2/neu–positive patients were treated with TPCG. The median number of cycles was six (range, 1 to 12 cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3 cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one tachycardia). There were two therapy-related deaths. Thirty-one (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44 were confirmed responses. Median time to progression and survival were 9.3 and 14.1 months, respectively. Conclusion We prospectively characterized Her-2/neu status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac toxicity rates were higher than projected, but the majority were grade two or lower. Determining the true contribution of trastuzumab requires a randomized trial.

Human Epidermal Growth Factor Receptor 2 Status Correlates With Lymph Node Involvement in Patients With Estrogen Receptor (ER) –Negative, but With Grade in Those With ER-Positive Early-Stage Breast Cancer Suitable for Cytotoxic Chemotherapy

2007 ◽  
Vol 25 (28) ◽  
pp. 4423-4430 ◽  
Author(s):  
John M.S. Bartlett ◽  
Ian O. Ellis ◽  
Mitch Dowsett ◽  
Elizabeth A. Mallon ◽  
David A. Cameron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Nodal Metastasis ◽  
Breast Cancers ◽  
Node Negative ◽  
Tumor Pathology ◽  
Er Positive ◽  
Her 2 ◽  
Epidermal Growth ◽  
Grade 3

Purpose Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation. Patients and Methods Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative). Results A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76). Conclusion In early breast cancer patients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2–mediated cross talk.

scholarly journals Histopathological study of epithelial ovarian tumors with special reference to human epidermal growth factor receptor-2/NEU and CA-125 expression

2021 ◽  
Vol 9 (6) ◽  
pp. 1628
Author(s):  
Shobnam Bahar Barbhuiya ◽  
Ananya Debnath ◽  
Monoj Kumar Deka ◽  
Shah Alam Sheikh
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Growth Factor Receptor ◽  
Tissue Expression ◽  
Ovarian Tumors ◽  
Ca 125 ◽  
Histopathological Study ◽  
Her 2 ◽  
Epidermal Growth ◽  
Grade 3

Background: Ovarian cancer is the second most common gynecologic malignancy. The aim of the study was to evaluate the tissue expression of HER-2/NEU and CA-125 in various epithelial ovarian carcinoma and assess the prognostic significance.Methods: A retrospective study was done in 76 cases of ovarian tumor. IHC was done in 16 cases of epithelial ovarian cancer with HER-2/NEU and CA-125.Results: Total number of cases were 76. Out of these 76 cases, 22 cases were malignant. 16 cases were malignant epithelial ovarian cancer. The highest incidence of malignant tumor was seen in the 41-50 years age group with 9 cases (11.84%). Out of 11 serous adenocarcinoma, 9 cases (81.8%) showed tissue expression of CA-125 and rest 2 cases (18.18%) did not show expression. All the 5 cases (100%) of mucinous adenocarcinoma did not show any tissue expression of CA-125. HER-2/NEU expression was positive in 7 out of 16 cases that is 43.75% and negative expression was seen in 9 out of 16 cases that is 56.25% of cases. Maximum HER-2/NEU positivity is seen among grade 3 tumors, that is (62.5%) (5 out of 8 cases).  Conclusions: The incidence of epithelial ovarian tumors are more common. The tissue expression of CA-125 on malignant epithelial ovarian tumors was studied, which showed positive expression in serous cystadenocarcinomas, but not in mucinous cystadenocarcinoma. HER-2/NEU expression was seen to be increasing with advanced grade of the tumors.

Young Age at Diagnosis Correlates With Worse Prognosis and Defines a Subset of Breast Cancers With Shared Patterns of Gene Expression

2008 ◽  
Vol 26 (20) ◽  
pp. 3324-3330 ◽  
Author(s):  
Carey K. Anders ◽  
David S. Hsu ◽  
Gloria Broadwater ◽  
Chaitanya R. Acharya ◽  
John A. Foekens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Young Women ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Egfr Expression ◽  
Her 2 ◽  
Epidermal Growth

Purpose Breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. The biology driving this aggressive disease has yet to be defined. Patients and Methods Clinically annotated, microarray data from 784 early-stage breast cancers were identified, and prospectively defined, age-specific cohorts (young: ≤ 45 years, n = 200; older: ≥ 65 years, n = 211) were compared by prognosis, clinicopathologic variables, mRNA expression values, single-gene analysis, and gene set enrichment analysis (GSEA). Univariate and multivariate analyses were performed. Results Using clinicopathologic variables, young women illustrated lower estrogen receptor (ER) positivity (immunohistochemistry [IHC], P = .027), larger tumors (P = .012), higher human epidermal growth factor receptor 2 (HER-2) overexpression (IHC, P = .075), lymph node positivity (P = .008), higher grade tumors (P < .0001), and trends toward inferior disease-free survival (DFS; hazard ratio = 1.32; P = .094). Using genomic expression analysis, tumors arising in young women had significantly lower ERα mRNA (P < .0001), ERβ (P = .02), and progesterone receptor (PR) expression (P < .0001), but higher HER-2 (P < .0001) and epidermal growth factor receptor (EGFR) expression (P < .0001). Exploratory analysis (GSEA) revealed 367 biologically relevant gene sets significantly distinguishing breast tumors arising in young women. Combining clinicopathologic and genomic variables among tumors arising in young women demonstrated that younger age and lower ERβ and higher EGFR mRNA expression were significant predictors of inferior DFS. Conclusion This large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways, is characterized by less hormone sensitivity and higher HER-2/EGFR expression, and warrants further study to offer this poor-prognosis group of women better preventative and therapeutic options.

Sign in / Sign up

Export Citation Format

Share Document