TP53 Germline Mutations are Associated with HR+/HER2+ in BRCA1/2-Negative Early-Onset Breast Cancer in China

2022 ◽  
Author(s):  
Lili Chen ◽  
Meng Huang ◽  
Minyan Chen ◽  
Yuxiang Lin ◽  
Jing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Tp53 Mutation ◽  
Sporadic Breast Cancer ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Early Onset Breast Cancer ◽  
Her 2 ◽  
Epidermal Growth ◽  
The Relationship

Abstract Background: Except for BRCA1/2, there is no data on the relationship between genetic counseling for the range of mutations and early-onset breast cancer populations. We looked for a link between inherited genes and the molecular subtype of early-onset breast cancer.Methods: We genotyped 1214 individuals with early-onset sporadic breast cancer (age≤40 years) who were BRCA1/2-negative in 3 genes: TP53, PALB2, and RECQL. We focus on the immunohistochemistry characteristics that are unique to each patient. Results: The mutation rates of TP53, PALB2, and RECQL in 1214 BRCA-negative young individuals were 4/1214(0.33%), 8/1214(0.66%), 2/1214(0.16%), respectively. The fact that the TP53 mutation rate was 3.49% among estrogen receptor-and/or progesterone receptor-positive, human epidermal growth factor receptor 2 (HER-2) amplification patients under the age of 35 (P<0.001) was particularly noteworthy. Conclusion: According to the findings, TP53 genetic testing should focus on women under 35 with HR-positive and HER2-positve IDC patients.

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 Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Jesse S. Chen ◽  
Jingwen Chen ◽  
Somnath Bhattacharjee ◽  
Zhengyi Cao ◽  
Han Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Tumor Imaging ◽  
Growth Factor Receptor ◽  
Therapeutic Monitoring ◽  
Mouse Tumor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Magnetic Resonance Imaging Mri

Abstract Background Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent. Results Testing in two mouse tumor models confirms this contrast agent’s ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells. Conclusion These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.

scholarly journals Phase II Trial of Lapatinib for Brain Metastases in Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1993-1999 ◽  
Author(s):  
Nancy U. Lin ◽  
Lisa A. Carey ◽  
Minetta C. Liu ◽  
Jerry Younger ◽  
Steven E. Come ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Brain Metastases ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

PurposeOne third of women with advanced human epidermal growth factor receptor 2 (HER-2)–positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither well-studied nor established. We evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2, in patients with HER-2–positive brain metastases.Patients and MethodsPatients had HER-2–positive breast cancer, progressive brain metastases, prior trastuzumab treatment, and at least one measurable metastatic brain lesion. Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. The primary end point was objective response (complete response [CR] plus partial response [PR]) in the CNS by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included objective response in non-CNS sites, time to progression, overall survival, and toxicity.ResultsThirty-nine patients were enrolled. All patients had developed brain metastases while receiving trastuzumab; 37 had progressed after prior radiation. One patient achieved a PR in the brain by RECIST (objective response rate 2.6%, 95% conditional CI, 0.21% to 26%). Seven patients (18%) were progression free in both CNS and non-CNS sites at 16 weeks. Exploratory analyses identified additional patients with some degree of volumetric reduction in brain tumor burden. The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%).ConclusionThe study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER-2–positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point.

Expression Analyses of Epidermal Growth Factor Receptor and HER-2/neu: No Advantage of Prediction of Recurrence or Survival in Breast Cancer Patients

Oncology ◽  
1996 ◽  
Vol 53 (6) ◽  
pp. 441-447 ◽  
Author(s):  
Matthias W. Beckmann ◽  
Dieter Niederacher ◽  
Gero Massenkeil ◽  
Boris Tutschek ◽  
Andreas Beckmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Epidermal Growth

scholarly journals Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer

2008 ◽  
Vol 26 (34) ◽  
pp. 5544-5552 ◽  
Author(s):  
Angelo Di Leo ◽  
Henry L. Gomez ◽  
Zeba Aziz ◽  
Zanete Zvirbule ◽  
Jose Bines ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2 ◽  
Epidermal Growth

PurposeLapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2–positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2–negative and HER-2–uncharacterized MBC.Patients and MethodsWomen with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m2every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS).ResultsIn the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2–negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms.ConclusionPatients with HER-2–negative or HER-2–untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2–positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2–positive breast cancer patients.

scholarly journals Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer

Cancer ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 2337-2345 ◽  
Author(s):  
Christopher Souder ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Laurence Demers ◽  
Dean B. Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Poor Survival ◽  
Her 2 ◽  
Epidermal Growth

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 A Cocktail of Specific Inhibitors of HER-2, PI3K, and mTOR Radiosensitises Human Breast Cancer Cells

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Roswita Hamunyela ◽  
Antonio Serafin ◽  
Mogammad Hamid ◽  
Sechaba Maleka ◽  
Daniel Achel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Her 2 ◽  
Epidermal Growth ◽  
Specific Inhibitors

Intrinsic tumour radioresistance limits the benefit of radiotherapy. Targeted treatment modalities that are singly effective for triple-negative breast cancer are lacking, partly due to paucity of relevant targets as they are devoidof the human epidermal growth factor receptor 2 (HER-2), progesterone receptor (PR), and oestrogen receptor (ER); or to resistance to single-target therapies as a consequence of cellular heterogeneity. Concomitant targeting of cell signaling entities other than HER-2, PR and ER may sensitise triple-negative tumours to radiotherapy. In this study, we investigated the effect of an HER-2 inhibitor (TAK-165) and a dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) (NVP-BEZ235) in three human breast cancer cell lines. The potential of simultaneous inhibition of HER-2, PI3K and mTOR with a cocktail of the specific inhibitors TAK-165 and NVP-BEZ235, to radiosensitise human breast cancer cells in vitro was examined using the colony forming assay. Combined inhibition of HER-2, PI3K, and mTOR resulted in significant radiosensitisation in all cell lines, independent of HER-2, ER, or PR status. Radiosensitisation was more prominent in ER- and PR-negative cells expressing higher levels of epidermal growth factor receptor (EGFR). These data suggest that a cocktail of TAK-165 and NVP-BEZ235 could potentially be effective in the treatment of triple-negative breast cancer. 

scholarly journals Human epidermal growth factor receptor 2/neu and the clinico-pathological profile in breast cancer: an observational study at a tertiary care hospital in Central India

2021 ◽  
Vol 8 (12) ◽  
pp. 3649
Author(s):  
Shikha Shukla ◽  
Fahad Ansari
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Breast Carcinoma ◽  
Epidermal Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
Epidermal Growth

Background: Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. Owing to a unique pattern of presentation in terms of clinical and biological features, finding their mutual association may be important and may help predict prognosis. HER2 (human epidermal growth factor receptor 2)/neu is one such important immunohistochemical factor that is considered to be more prevalent amongst Indians and therefore makes up for an emerging area for studies. The study aimed to assess the patients of breast carcinoma in terms of their HER2/neu statuses and find out their association with clinical parameters.Methods: This was a prospective comparative study conducted in department of surgery, Hamidia hospital, Bhopal, India, with a total duration of 1 year between November 2018 to September 2019 including a total of 98 consecutive in house breast carcinoma patients.Results: A total of 98 breast cancer patients were tested for HER-2/neu gene presence. Of these 25 (25.5%) samples tested positive and 73 (7.48%) tested negative. A comparison of the two groups revealed that none of the clinic-pathological factors tested were found to have a statistically significant association with the HER2/neu status.Conclusions: It appeared that there is no defining factor in terms of clinic-pathological presentation that helps to separate significantly HER-2/neu positive with HER-2/neu negative cases with breast cancer. Still, immune-histochemical marker analysis should be an integral part of the overall work up of the breast cancer patients because of its both prognostic and therapeutic application and significance.

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