Ki67 as Proliferative Marker in Patients with Early Breast Cancer and Its Association with Clinicopathological Factors

Oncology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Amelie de Gregorio ◽  
Thomas Wolfram Paul Friedl ◽  
Eva Hering ◽  
Peter Widschwendter ◽  
Nikolaus de Gregorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
University Hospital ◽  
Proliferation Index ◽  
Her2 Status ◽  
Clinicopathological Factors ◽  
Her2 Positive ◽  
Proliferative Marker

<b><i>Introduction:</i></b> Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. <b><i>Material and Methods:</i></b> Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (<i>n</i> = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. <b><i>Results:</i></b> 595 (64.9%) patients had a Ki67 &#x3c;20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1–90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2−) disease (<i>n</i> = 717), 20% for HR+/HER2+ (<i>n</i> = 76), 30% for HR−/HER2+ (<i>n</i> = 45), and 60% for HR−/HER2− (<i>n</i> = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (&#x3c;20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%). <b><i>Conclusion:</i></b> This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

scholarly journals Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.

scholarly journals Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer

2021 ◽  
Author(s):  
Tilman D. Rachner ◽  
Sabine Kasimir-Bauer ◽  
Andy Goebel ◽  
Kati Erdmann ◽  
Oliver Hoffmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Therapeutic Potential ◽  
Transmembrane Protein ◽  
Tumor Biology ◽  
Tumor Stage ◽  
Her2 Status ◽  
Tyrosine Kinase Receptor ◽  
Neuropilin 1

Abstract Background Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies. Materials and methods We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA. Results Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23–3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09–2.91). Conclusion Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

Cost Effectiveness of Adjuvant Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2007 ◽  
Vol 25 (6) ◽  
pp. 625-633 ◽  
Author(s):  
Nicola Lucio Liberato ◽  
Monia Marchetti ◽  
Giovanni Barosi
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Early Breast Cancer ◽  
Growth Factor Receptor ◽  
Local Relapse ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Life Years ◽  
Epidermal Growth ◽  
The Cost

Purpose To evaluate the cost-effectiveness of 12-month adjuvant trastuzumab therapy in women with high-risk human epidermal growth factor receptor 2 (HER2) –positive early breast cancer. Methods A Markov model tracked quarterly patients’ transitions between five health states: disease free, local relapse, disease free after local relapse, metastatic disease, and death. Patients were allowed to incur symptomatic or asymptomatic transient cardiac dysfunction during trastuzumab administration. Probabilities were derived mainly from the combined report of the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials (95% node positive) and a meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group. Costs were estimated from the perspective of the Italian and US health care systems. The analysis was run during a 15-year time horizon. A 3% yearly discount rate was applied to both costs and life-years. Second-order Monte-Carlo and probabilistic sensitivity analyses were performed. Results Adjuvant trastuzumab increases life expectancy by 1.54 (1.18 discounted) quality-adjusted life-years (QALYs). At a cost of €675 and $767 per weekly dose in the Italian and US setting, respectively, trastuzumab achieves its clinical benefit at a cost of €14,861 (95% CI, €3,917 to €44,028) and $18,970 (95% CI, $6,014 to $45,621) per QALY saved. The incremental cost effectiveness was higher than €50,000/QALY (or $60,000/QALY) at time horizons shorter than 7.8 years and for patients older than 76 years or with a 10-year risk of relapse lower than 15%. The results confirmed the cost effectiveness when simulating a Herceptin Adjuvant Trial (HERA) -like scenario at multiway sensitivity analysis. Conclusion In a long-term horizon, adjuvant trastuzumab is a cost-effective therapy for patients with HER2-positive, high-risk, early breast cancer.

scholarly journals Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors

2012 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Naoki Niikura ◽  
Jun Liu ◽  
Naoki Hayashi ◽  
Elizabeth A. Mittendorf ◽  
Yun Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Breast Tumors ◽  
Her2 Status ◽  
Her2 Positive ◽  
Metastatic Tumors ◽  
Epidermal Growth

Purpose We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) –positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors. Patients and Methods We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review. Results We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies. Conclusion We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.

Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6097-6097
Author(s):  
P. Scullin ◽  
A. T. Drake ◽  
V. M. Coyle ◽  
J. J. McAleer
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Number Of Patients

6097 Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p<0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease. No significant financial relationships to disclose.

scholarly journals Outcomes by Tumor Subtype and Treatment Pattern in Women With Small, Node-Negative Breast Cancer: A Multi-Institutional Study

2014 ◽  
Vol 32 (20) ◽  
pp. 2142-2150 ◽  
Author(s):  
Ines Vaz-Luis ◽  
Rebecca A. Ottesen ◽  
Melissa E. Hughes ◽  
Rizvan Mamet ◽  
Harold J. Burstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Survival Outcomes ◽  
Breast Cancers ◽  
Tumor Subtype ◽  
Her2 Positive ◽  
Distant Relapse ◽  
Node Negative Breast Cancer

Purpose Treatment decisions for patients with T1a,bN0M0 breast cancer are challenging. We studied the time trends in use of adjuvant chemotherapy and survival outcomes among these patients. Patients and Methods This was a prospective cohort study within the National Comprehensive Cancer Network Database that included 4,113 women with T1a,bN0M0 breast cancer treated between 2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. Results Median follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2-negative tumors were treated with chemotherapy. Fifty-two percent of those with HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy, with an increase over the last decade. Survival outcomes diverged by subtype and size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in any subgroup. The 5-year DRFS for patients with T1a tumors untreated with chemotherapy ranged from 93% to 98% (n = 49 to 972), and for patients with T1b tumors, it ranged from 90% to 96% (n = 17 to 2,005). Patients with HR-positive/HER2-negative disease had the best DRFS estimates, and patients with HR-negative/HER2-negative tumors had the lowest. In this observational, nonrandomized cohort study, the 5-year DRFS for treated patients with T1a tumors was 100% for all subgroups (n = 12 to 33), and for patients with T1b tumors, it ranged from 94% to 96% (n = 88 to 241). Conclusion Women with T1a,b tumors have an excellent prognosis without chemotherapy. Size and tumor subtype may identify patients in whom the rate of recurrence justifies consideration of chemotherapy. These patients represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.

De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor–Positive Phase II Randomized Trial—Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET

2017 ◽  
Vol 35 (26) ◽  
pp. 3046-3054 ◽  
Author(s):  
Nadia Harbeck ◽  
Oleg Gluz ◽  
Matthias Christgen ◽  
Ronald Ernest Kates ◽  
Michael Braun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Growth Factor Receptor ◽  
Therapy Response ◽  
Response Prediction ◽  
Early Response ◽  
Her2 Positive ◽  
The West ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Purpose Human epidermal growth factor receptor 2 (HER2)–positive/hormone receptor (HR)–positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen therapy-related severe adverse events (T-DM1 arms v trastuzumab plus ET; 5.3% v 3.1%, respectively) were reported. Conclusion The ADAPT HER2-positive/HR-positive trial demonstrates that neoadjuvant T-DM1 (with or without ET) given for only 12 weeks results in a clinically meaningful pCR rate. Thus, a substantial number of patients are spared the adverse effects of systemic chemotherapy.

scholarly journals Peptide Based Imaging Agents for HER2 Imaging in Oncology

2020 ◽  
Vol 19 ◽  
pp. 153601212096025 ◽  
Author(s):  
Maxwell Ducharme ◽  
Suzanne E. Lapi
Keyword(s):  
Breast Cancer ◽  
Pet Imaging ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Cancer Type ◽  
Her2 Positive ◽  
Positron Emission ◽  
Imaging Probes

Breast cancer continues to be the most lethal cancer type in women and one of the most diagnosed. Understanding Breast cancer receptor status is one of the most vital processes for determining treatment options. One type of breast cancer, human epidermal growth factor receptor 2 (HER2) positive, has approved receptor-based therapies including trastuzumab and pertuzumab that can significantly increase the likelihood of survival. Current methods to determine HER2 status include biopsies with immunohistochemical staining and/or fluorescence in situ hybridization. However, positron emission tomography (PET) imaging techniques using 89Zr-trastuzumab or 89Zr-pertuzumab are currently in clinical trials for a non-invasive, full body diagnostic approach. Although the antibodies have strong specificity to the HER2 positive lesions, challenges involving long post-injection time for imaging due to the blood circulation of the antibodies and matching of long-live isotopes leading to increased dose to the patient leave opportunities for alternative PET imaging probes. Peptides have been shown to allow for shorter injection-to-imaging time and can be used with shorter lived isotopes. HER2 specific peptides under development will help improve the diagnosis and potentially therapy options for HER2 positive breast cancer. Peptides showing specificity for HER2 could start widespread development of molecular imaging techniques for HER2 positive cancers.

Sign in / Sign up

Export Citation Format

Share Document