Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

Neratinib in HER2-Positive Breast Cancer Patients

2019 ◽  
Vol 53 (6) ◽  
pp. 612-620 ◽  
Author(s):  
Rutugandha Paranjpe ◽  
Dima Basatneh ◽  
Gabriel Tao ◽  
Carmine De Angelis ◽  
Sobia Noormohammed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Common Adverse Effect ◽  
Stage I ◽  
Phase Iii ◽  
Therapeutic Window ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Safety And Efficacy ◽  
Her2 Breast Cancer

Objective:To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib in human epidermal growth factor receptor (HER2)+ breast cancer (BC). Data Sources: A PubMed search was performed using the term neratinib between September 12, 2018, and November 21, 2018. References of published articles and reviews were also assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib were evaluated. Data Synthesis: Neratinib, an irreversible inhibitor of HER1, HER2, and HER4, is Food and Drug Administration approved for the extended adjuvant treatment of stage I-III HER2+ BC to follow trastuzumab-based therapy. A phase III study has demonstrated statistically significant improvement in 5-year disease-free survival rate (90.2 vs 87.7; hazard ratio = 0.73, 95% CI = 0.57-0.92, P = 0.0083). Its most common adverse effect is diarrhea, observed in more than 90% of patients. The incidence of grade 3/4 diarrhea (~40%) is reduced by half with loperamide prophylaxis, which is recommended for the first 8 weeks of neratinib therapy. Other common adverse reactions are nausea and fatigue. The patients need to be monitored for liver function tests and drug interactions with acid-reducing agents, CYP3A4 inhibitors/inducers, and P-glycoprotein substrates with narrow therapeutic window. Relevance to Patient Care and Clinical Practice: American Society of Clinical Oncology and National Comprehensive Cancer Network clinical guidelines suggest the use of neratinib for extended adjuvant therapy following 1-year trastuzumab in stage I to III HER2+ BC. Diarrhea remains a clinically significant but manageable adverse event. Conclusion: Neratinib significantly improves treatment outcomes and has manageable toxicity in stage I to III HER2+ BC patients.

Population-based outcomes of patients (pt) with early-stage HER2-positive breast cancer treated with adjuvant trastuzumab (T).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11079-e11079
Author(s):  
Krista Noonan ◽  
Joy S. McCarthy
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Early Stage ◽  
Tumour Size ◽  
Disease Free Survival ◽  
Clinical Effectiveness ◽  
Population Based ◽  
The Body ◽  
Phase Iii ◽  
Her2 Positive

e11079 Background: Phase III trials have shown clinical efficacy of T when combined with chemotherapy in HER2-positive early stage breast cancer, decreasing recurrence by 50% and increasing survival by 30%. 15-20% of early stage breast cancers demonstrate amplification of the HER2 gene, which is associated with a poor prognosis. The aims of this study were to evaluate the clinical effectiveness of T, and explore potential prognostic factors. Methods: Pts with stage I-III breast cancer overexpressing HER2 from 2005 to 2010, assessed in Newfoundland and Labrador’s cancer centre were retrospectively identified from the Provincial Tumour Registry. Pt, treatment, and tumour characteristics were extracted. Kaplan-Meier curves were used for survival analysis, and Cox Proportional Hazards Models were used to identify prognostic factors and evaluate their impact on outcomes. Results: A total of 148 pts were identified. The median age was 56 years, and 76% received T. At a median follow-up of 25 months, overall survival (OS) was 97% (p=0.0002), and disease-free survival was 96% (p<0.00) for pts receiving T. Younger age, smaller tumour size, and lymph node negativity were favorable prognostic factors. There was an 83% decrease in risk of breast cancer recurrence in the patients receiving T. Discontinuation of T occurred in 6.2% of patients due to a decreased ejection fraction. Conclusions: This population-based analysis demonstrates T’s favorable impact on 25-month DFS, OS, and safety. This adds to the body of literature, showing clinical effectiveness and tolerability of T. [Table: see text]

Association of Caspase 8 polymorphisms with TILs and disease-free survival in primary breast cancer patients.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24258-e24258
Author(s):  
Pauline Wimberger ◽  
Hagen Sjard Bachmann ◽  
Jan Dominik Kuhlmann ◽  
Theresa Link ◽  
Eric Kroeber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Disease Free Survival ◽  
Caspase 8 ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

scholarly journals Clinical Development of the E75 Vaccine in Breast Cancer

Breast Care ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Guy T. Clifton ◽  
Victor Gall ◽  
George E. Peoples ◽  
Elizabeth A. Mittendorf
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Protein A ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Initial Step ◽  
Recurrence Risk ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Gm Csf

E75 is an immunogenic peptide derived from the human epidermal growth factor receptor 2 (HER2) protein. A large amount of preclinical work evaluated the immunogenicity of E75, after which phase I trials investigated using E75 mixed with an immunoadjuvant as a vaccine. Those studies showed the vaccine to be safe and capable of stimulating an antigen-specific immune response. Subsequent to that, our group conducted trials evaluating E75 + granulocyte macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting. The studies enrolled node-positive and high-risk node-negative breast cancer patients, with the goal being to determine if vaccination could decrease the recurrence risk. The studies included 187 evaluable patients: 108 vaccinated ones and 79 controls. The 5-year disease-free survival for the vaccinated patients was 89.7% compared to 80.2% for the control patients, a 48% reduction in relative risk of recurrence. Based on these data, E75 + GM-CSF, now known as NeuVax™, is being evaluated in a phase III trial. In this article, we review preclinical data and results of the early-phase trials and provide an update on the ongoing phase III study. We also present additional strategies for employing the vaccine to be included as a component of combination immunotherapy as well as in the setting of ductal carcinoma in situ as an initial step towards primary prevention.

scholarly journals Systemic control and encephalic response with lapatinib plus capecitabine as second-line therapy in HER2-positive, metastatic breast cancer

ABOUTOPEN ◽  
2018 ◽  
Vol 4 (1) ◽  
pp. 110-115
Author(s):  
Raffaele Ardito ◽  
Fiorella Restaino Marino
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival ◽  
Systemic Control ◽  
Epidermal Growth

Overexpression of the human epidermal growth factor receptor (HER2) oncoprotein in breast cancer patients, is one of the biological characteristics of the disease that determines the choice of appropriate systemic treatment. We report the case of a 41-year-old woman, with relapsing HER2-positive breast cancer in cerebral and pulmonary cells. The patient underwent multimodal first Iine treatment including pertuzumab, trastuzumab and docetaxel and panencephalic radiotherapy with good response and progression-free survival for approximately 16 months. Subsequently, further to a encephalic progression of the disease, the patient was treated in second line with the combination lapatinib + capecitabine which induced further encephalic response and disease control for additional 20 months (Oncology).

scholarly journals Prognostic factors of brain metastasis and survival among HER2-positive metastatic breast cancer patients: a systematic literature review

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Michelle D. Hackshaw ◽  
Heather E. Danysh ◽  
Mackenzie Henderson ◽  
Eric Wang ◽  
Nora Tu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Literature Review ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Two Phase ◽  
Her2 Breast Cancer

Abstract Background Patients with breast cancer who overexpress the human epidermal growth factor receptor 2 (HER2) and subsequently develop brain metastasis (BM) typically experience poor quality of life and low survival. We conducted a comprehensive literature review to identify prognostic factors for BM and predictors of survival after developing BM, and the effects of therapies with different mechanisms of action among patients with HER2+ breast cancer (BC). Methods A prespecified search strategy was used to identify research studies investigating BM in patients with HER2+ BC published in English during January 1, 2009–to June 25, 2021. Articles were screened using a two-phase process, and data from selected articles were extracted. Results We identified 25 published articles including 4097 patients with HER2+ BC and BM. Prognostic factors associated with shorter time to BM diagnosis after initial BC diagnosis included younger age, hormone receptor negative status, larger tumor size or higher tumor grade, and lack of treatment with anti-HER2 therapy. Factors predictive of longer survival after BM included having fewer brain lesions (< 3 or a single lesion) and receipt of any treatment after BM, including radiosurgery, neurosurgery and/or systemic therapy. Patients receiving combination trastuzumab and lapatinib therapy or trastuzumab and pertuzumab therapy had the longest median survival compared with other therapies assessed in this review. Conclusions More research is needed to better understand risk factors for BM and survival after BM in the context of HER2+ BC, as well as the assessment of new anti-HER2 therapy regimens that may provide additional therapeutic options for BM in these patients.

scholarly journals A Novel Prognostic Nomogram for the 2-year Survival in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients

2021 ◽  
Author(s):  
Mengdi Chen ◽  
Jiayi Wu ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Seer Database ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Abstract Background: Targeted therapies have largely improved prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Yet, disease can still progress rapidly for some patients in the first two years after diagnosis. Our study aimed to establish a nomogram model to predict the 2-year breast cancer-specific survival (BCSS) in early HER2-positive breast cancer patients. Methods: A total of 32,481 HER2-positive patients derived from Surveillance, Epidemiology, and End Results (SEER) database were included in the construction of nomogram. Concordance index (C-index) and calibration curve were used to evaluate the discrimination ability and predictive accuracy. We tested the model in 804 patients from Shanghai Jiao Tong University Breast Cancer Data Base (SJTU-BCDB). Results: Age, estrogen receptor (ER) status, progesterone receptor (PR) status, histologic type, T stage and N stage were selected to construct the nomogram according to multivariable analysis. The 2-year BCSS rate was 95% and 60% for patients at low risk (<8 points) and high risk (>13 points) respectively. The C-index of model derived from SEER database is 0.81 (95%CI 0.79-0.83). Sensitivity analysis was performed in patients after breast surgeries with the C-index of 0.81 (95%CI, 0.79-0.83). Validation in 804 patients from SJTU-BCDB showed respective C-index of 0.77 (95%CI, 0.62-0.92) in total population, 0.67 (95%CI 0.44-0.90) and 0.90 (95%CI 0.81-0.90) in patients who received anti-HER2 therapy or not. Discussion: The novel nomogram can predict the 2-year survival outcome in HER2-positive patients independent of receiving anti-HER2 therapy or not and allow clinicians to adjust therapeutic strategies for patients with higher risk.

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.

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