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.

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

HER-2-Amplified Breast Cancer

2018 ◽  
Author(s):  
Zahraa Al-Hilli ◽  
Judy C Boughey
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Aggressive Disease ◽  
Node Positive Disease ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Amplification of the human epidermal growth factor receptor–2 (HER-2) gene is found in approximately 15 to 30% of breast cancers. Historically, HER-2 overexpression has been associated with aggressive disease and a poor prognosis. However, the use of targeted anti-HER2 therapy has revolutionized the treatment of HER-2-positive disease, and the use of the monoclonal antibody trastuzumab in combination with chemotherapy is now standard of care for tumors greater than 1 cm in size and in node-positive disease. More recently, the value of dual-agent anti-HER-2 therapy has been demonstrated in large clinical trials. This review provides an overview of HER-2-positive breast cancer, its molecular basis, methods of identification, and treatment options and strategies. This review contains 2 figures and 70 references Key words: anti-HER-2 therapy, breast cancer, HER-2-positive breast cancer, HER-2 resistance, lapatinib, neoadjuvant chemotherapy, pertuzumab, small HER-2-positive breast cancer, trastuzumab

Human Epidermal Growth Factor Receptor 2 Overexpression As a Prognostic Factor in a Large Tissue Microarray Series of Node-Negative Breast Cancers

2008 ◽  
Vol 26 (35) ◽  
pp. 5697-5704 ◽  
Author(s):  
Stephen Chia ◽  
Brian Norris ◽  
Caroline Speers ◽  
Maggie Cheang ◽  
Blake Gilks ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Prognostic Factor ◽  
Growth Factor Receptor ◽  
Her2 Overexpression ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Epidermal Growth

Purpose Human epidermal growth factor receptor 2 gene (HER2) is associated with a poorer outcome in node-positive breast cancer, but the results are conflicting in node-negative disease. This study assessed the prognostic impact of HER2 overexpression/amplification in a large series of node-negative breast cancers. Patients and Methods A tissue microarray (TMA) series was constructed consisting of 4,444 invasive breast cancers diagnosed in British Columbia from 1986 to 1992. Within this series, 2,026 patients were node negative, of whom 70% did not receive adjuvant systemic therapy. The TMA series was assessed for estrogen receptor (ER) and HER2. Logistic regression modeling was used to estimate odds ratios at the 10-year follow-up. Results HER2 was positive in 10.2% of the node-negative cohort. In this cohort, an inferior outcome was seen in patients with HER2-positive tumors compared with HER2-negative tumors for 10-year relapse-free survival (RFS; 65.9% v 75.5%, respectively; P = .01), distant RFS (71.2% v 81.8%, respectively; P = .004), and breast cancer–specific survival (BCSS; 75.5% v 86.3%, respectively; P = .001). A trend for a worse overall survival was also seen (P = .06). HER2 was an independent poor prognostic factor for RFS and BCSS at 10 years, with odds ratios of 1.71 (P = .01) and 2.03 (P = .003), respectively. The number of HER2-positive tumors that were ≤ 1 cm was small, but there was a trend for a worse outcome in T1b tumors. Conclusion HER2 overexpression/amplification is correlated with a poorer outcome in node-negative breast cancer. Larger studies are needed to more clearly define the prognostic impact of HER2 in tumors ≤ 1 cm, particularly within the separate hormone receptor subgroups.

scholarly journals The Research Progress of Trastuzumab-Induced Cardiotoxicity in HER-2-Positive Breast Cancer Treatment

2022 ◽  
Vol 8 ◽  
Author(s):  
Mengmeng Lin ◽  
Weiping Xiong ◽  
Shiyuan Wang ◽  
Yingying Li ◽  
Chunying Hou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Research Progress ◽  
High Recurrence Rate ◽  
Breast Cancers ◽  
Humanized Monoclonal Antibody ◽  
Application Potential ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

In recent years, the incidence of breast cancer has been increasing on an annual basis. Human epidermal growth factor receptor-2 (HER-2) is overexpressed in 15-20% human breast cancers, which is associated with poor prognosis and a high recurrence rate. Trastuzumab is the first humanized monoclonal antibody against HER-2. The most significant adverse effect of trastuzumab is cardiotoxicity, which has become an important factor in limiting the safe use of the drug. Unfortunately, the mechanism causing this cardiotoxicity is still not completely understood, and the use of preventive interventions remains controversial. This article focuses on trastuzumab-induced cardiotoxicity, reviewing the clinical application, potential cardiotoxicity, mechanism and discussing the potential interventions through summarizing related researches over the past tens of years.

scholarly journals High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller

2009 ◽  
Vol 27 (34) ◽  
pp. 5700-5706 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Jennifer K. Litton ◽  
Kristine R. Broglio ◽  
Funda Meric-Bernstam ◽  
Ronjay Rakkhit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Distant Recurrence ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Node Negative ◽  
Epidermal Growth

Purpose To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) –positive breast cancer. Methods We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence–free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Results Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor–positive tumors. Conclusion Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

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.

HER-2-Amplified Breast Cancer

2018 ◽  
Author(s):  
Zahraa Al-Hilli ◽  
Judy C Boughey
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Aggressive Disease ◽  
Node Positive Disease ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Amplification of the human epidermal growth factor receptor–2 (HER-2) gene is found in approximately 15 to 30% of breast cancers. Historically, HER-2 overexpression has been associated with aggressive disease and a poor prognosis. However, the use of targeted anti-HER2 therapy has revolutionized the treatment of HER-2-positive disease, and the use of the monoclonal antibody trastuzumab in combination with chemotherapy is now standard of care for tumors greater than 1 cm in size and in node-positive disease. More recently, the value of dual-agent anti-HER-2 therapy has been demonstrated in large clinical trials. This review provides an overview of HER-2-positive breast cancer, its molecular basis, methods of identification, and treatment options and strategies. This review contains 2 figures and 70 references Key words: anti-HER-2 therapy, breast cancer, HER-2-positive breast cancer, HER-2 resistance, lapatinib, neoadjuvant chemotherapy, pertuzumab, small HER-2-positive breast cancer, trastuzumab

scholarly journals Trastuzumab

2005 ◽  
Vol 1 (2) ◽  
pp. 161-169
Author(s):  
Ian E Smith ◽  
Susan G Cross
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Humanized Monoclonal Antibody ◽  
Her 2 ◽  
Epidermal Growth ◽  
Chemotherapy Agents ◽  
Worse Prognosis

Breast cancer is a heterogenous disease with several clinical and biologic subtypes. Human epidermal growth factor receptor 2 (HER 2) is overexpressed in approximately 20% of breast cancers. This overexpression is usually due to HER 2 gene amplification, and results in a more aggressive tumor with a worse prognosis. Trastuzumab (Herceptin®) is the first humanized monoclonal antibody to be commercially available for the treatment of breast cancer and it is directed against HER 2. Trials have demonstrated trastuzumab's activity in metastatic breast cancer both as a single agent and in combination with a number of chemotherapy agents. Recently, benefits for trastuzumab have also been shown in the neoadjuvant and adjuvant setting.

scholarly journals Induction of Apoptosis in MDA-MB-231 Cells Treated with the Methanol Extract of Lichen Physconia hokkaidensis

2021 ◽  
Vol 7 (3) ◽  
pp. 188
Author(s):  
Ji-In Noh ◽  
Seul-Ki Mun ◽  
Eui Hyeon Lim ◽  
Hangun Kim ◽  
Dong-Jo Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Prolonged Exposure ◽  
Methanol Extract ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Er Positive ◽  
Her 2 ◽  
Induction Of Apoptosis ◽  
Mcf 7

Physconia hokkaidensis methanol extract (PHE) was studied to identify anticancer effects and reveal its mechanism of action by an analysis of cytotoxicity, cell cycles, and apoptosis biomarkers. PHE showed strong cytotoxicity in various cancer cells, including HL-60, HeLa, A549, Hep G2, AGS, MDA-MB-231, and MCF-7. Of these cell lines, the growth of MDA-MB-231 was concentration-dependently suppressed by PHE, but MCF-7 was not affected. MDA-MB-231 cells, triple-negative breast cancer (TNBC) cells, do not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), whereas MCF-7 cells are ER-positive, PR-positive, and HER-2-negative breast cancer cells. The number of cells in sub-G1 phase was increased after 24 h of treatment, and annexin V/PI staining showed that the population size of apoptotic cells was increased by prolonged exposure to PHE. Moreover, PHE treatment downregulated the transcriptional levels of Bcl-2, AMPK, and p-Akt, whereas it significantly upregulated the levels of cleaved caspase-3, cleaved caspase-9, and cleaved-PARP. In conclusion, it was confirmed that the PHE exhibited selective cytotoxicity toward MDA-MB-231, not toward MCF-7, and its cytotoxic activity is based on induction of apoptosis.

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