scholarly journals Peptide Based Imaging Agents for HER2 Imaging in Oncology

2020 ◽  
Vol 19 ◽  
pp. 153601212096025 ◽  
Author(s):  
Maxwell Ducharme ◽  
Suzanne E. Lapi

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.

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6482
Author(s):  
Shushan Ge ◽  
Jihui Li ◽  
Yu Yu ◽  
Zhengguo Chen ◽  
Yi Yang ◽  
...  

As the most frequently occurring cancer worldwide, breast cancer (BC) is the leading cause of cancer-related death in women. The overexpression of HER2 (human epidermal growth factor receptor 2) is found in about 15% of BC patients, and it is often associated with a poor prognosis due to the effect on cell proliferation, migration, invasion, and survival. As a result of the heterogeneity of BC, molecular imaging with HER2 probes can non-invasively, in real time, and quantitatively reflect the expression status of HER2 in tumors. This will provide a new approach for patients to choose treatment options and monitor treatment response. Furthermore, radionuclide molecular imaging has the potential of repetitive measurements, and it can help solve the problem of heterogeneous expression and conversion of HER2 status during disease progression or treatment. Different imaging probes of targeting proteins, such as monoclonal antibodies, antibody fragments, nanobodies, and affibodies, are currently in preclinical and clinical development. Moreover, in recent years, HER2-specific peptides have been widely developed for molecular imaging techniques for HER2-positive cancers. This article summarized different types of molecular probes targeting HER2 used in current clinical applications and the developmental trend of some HER2-specific peptides.


2012 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Naoki Niikura ◽  
Jun Liu ◽  
Naoki Hayashi ◽  
Elizabeth A. Mittendorf ◽  
Yun Gong ◽  
...  

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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6097-6097
Author(s):  
P. Scullin ◽  
A. T. Drake ◽  
V. M. Coyle ◽  
J. J. McAleer

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.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12584-e12584
Author(s):  
Serafin Morales Murillo ◽  
Ariadna Gasol Cudós ◽  
Joel Veas Rodriguez ◽  
Carles Canosa Morales ◽  
Jordi Melé Olivé ◽  
...  

e12584 Background: FDG-PET in clinical practice is based on the detection of a relapse and the initial staging but its role as a predictive factor or its correlation with biological parameters is very controversial. Methods: We analyzed the SUV of FDG-PET in a cohort with 36 patients in neoadjuvant setting and 112 with metastatic disease. Results: The median of SUV in neoadjuvant was 8,95 (range 2,8-30) with higher SUV in triple negative (11,7 range 2,8-18,8) than HER2 positive (8,75 range 4-30) and luminal patients (7,9 range 4,4-16). We don´t find a correlation between the SUV with either histological and clinical variables but there was a slightly correlation with residual tumor (p:0,068) and initial node involvement (p:0,069). In the 112 metastatic cohort the median SUV was 7,95 (range 2-28) with higher SUV in triple negative (10,1 range 3,4-19) than HER2 positive (9,7 range 4-28) and luminal patients (7,6 range 2.21). We found only a correlation between the SUV and progesterone receptor value (OR 0,875 p:0,005) but not in estrogen receptor, Ki67 index and HER2 status. In the survival analysis we don´t find a correlation between the SUV value and the disease free and overall survival included the analysis for different phenotypes. Conclusions: The SUV of the FDG-PET is very variable in all phenotypes of breast cancer being higher in the triple negative phenotype and lower in the luminal. The SUV value is very similar in neoadjuvant and metastatic setting. We only correlated the SUV value with the progesterone receptor in the metastatic cohort. We don´t find a prognostic value of the initial value of SUV in the two cohorts.


2014 ◽  
Vol 32 (20) ◽  
pp. 2142-2150 ◽  
Author(s):  
Ines Vaz-Luis ◽  
Rebecca A. Ottesen ◽  
Melissa E. Hughes ◽  
Rizvan Mamet ◽  
Harold J. Burstein ◽  
...  

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.


2015 ◽  
Vol 33 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Rachel J.D. Cossetti ◽  
Scott K. Tyldesley ◽  
Caroline H. Speers ◽  
Yvonne Zheng ◽  
Karen A. Gelmon

Purpose To determine whether the patterns of relapse according to estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status changed in the contemporary era. Patients and Methods Female patients referred to the British Columbia Cancer Agency with biopsy-proven stage I to III breast cancer (BC), diagnosed between 1986 and 1992 (cohort 1 [C1]) and between mid-2004 and 2008 (cohort 2 [C2]), and with known ER and HER2 status were eligible. Data were prospectively collected. C2 patients were matched to C1 patients for stage, grade, and ER and HER2 status. The primary end point was hazard rate of relapse (HRR) for BC by study cohort according to biomarker status. Secondary outcomes included HRR according to stage, grade, and age and hazard rate of death (HRD). Results After matching, 7,178 patients were included (3,589 patients in each cohort). BC subtype distribution was as following ER positive/HER2 negative, 70.8%; ER positive/HER2 positive, 6.9%; ER negative/HER2 positive, 6.6%; and ER negative/HER2 negative, 15.8%. For the overall population, the HRR approximately halved in all yearly intervals to year 9 in C2 compared with C1. Differences in HRR between cohorts were greater in the initial five intervals for HER2-positive and ER-negative/HER2-negative BC. The HRR decreased in C2 compared with C1 for all disease stages and grades. The HRD in C2 also decreased compared with C1, although to a lesser extent. Conclusion Although the pattern of relapse remains similar, there has been a significant improvement in BC relapse-free survival. Outcomes have improved for all BC subtypes, especially HER2-positive and ER-negative/HER2-negative BC, with the early spike in disease recurrence markedly decreased. These contemporary hazard rates are important for treatment decisions, patient discussions, and planning clinical trials of early BC.


2018 ◽  
Vol 07 (01) ◽  
pp. 07-10 ◽  
Author(s):  
Rekha Vijay Kumar ◽  
Dipti Panwar ◽  
Usha Amirtham ◽  
Chennagiri Srinivasmurthy Premalata ◽  
Champaka Gopal ◽  
...  

Abstract Aim: The aim of the study was to analyze the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7 years in South Indian women with breast cancer. Further analysis of a subgroup was done to study clinically defined subtypes and the role of preanalytical factors in needle core biopsies (NCBs) and excised specimens. Materials and Methods: This was a retrospective study from January 2010 to December 2016. Patients diagnosed with invasive breast cancer and available immunohistochemistry (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year 2016 were analyzed further to observe the impact of preanalytical factors on the IHC staining patterns and surrogate status. Results: A total of 5436 patients were included with a median age of 48 years. Among these, 65% were ≤ 55 years. The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2 positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in patients <56 years and over 55 years, respectively (P < 0.001). There was an increase in HR positivity and decrease in TNBCs over time. There was no significant difference in the staining patterns in NCBs and excised specimens. Conclusion: With time, there is an increase in hormone-positive tumors which may be attributed to better IHC techniques and tissue handling. There was no statistical difference in the patterns of ER, PR, and HER2 immunostaining in core biopsy and excised specimens.


2020 ◽  
Vol 9 (4) ◽  
pp. 935
Author(s):  
Florian Huemer ◽  
Lukas Weiss ◽  
Peter Regitnig ◽  
Thomas Winder ◽  
Bernd Hartmann ◽  
...  

Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870–24,530) vs. 6.9 months (95% CI: 3.980–9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.


2018 ◽  
Vol 16 (2) ◽  
pp. 48-50 ◽  
Author(s):  
Shakera Ahmed ◽  
Khondker AK Azad

Background: Estimation of Estrogen Receptor (ER) Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) is mandatory for choosing treatment options and prognosis of breast cancer patients. This estimation can be done by Immunohistochemistry (IHC) and Fluoroscence In Situ Hybridization (FISH) test. As the tests are expensive many of our patients can’t afford to do it. But if we practice doing the test routinely the cost will be reduced and our patients will be benefited. So we underwent a primitive study on receptor status in breast cancer patients. Our goal was to encourage the surgeons to advice receptor status routinely and treat the patients accordingly as patients prognosis will be much more better if they are treated according to their receptor status.Methods: This was a retrospective observational study of 74 breast cancer patients in a private clinic. In this study we have shown their receptor status by IHC and the data were analyzed.Results: Among the 74 patients 32 were ER +ve PR +ve, 11 were ER +ve PR -ve, 02 were ER –ve PR +ve, 29 were ER -ve PR -ve. ER &/or PR positive patients will be more responsive to hormone therapy. 28 patients were HER2 +ve, 34 patients were HER2 –ve and 9 were equivocal. HER2 positive patients will be benefited from targeted therapy. Among the patients 11 were triple negative that means they have worst prognosis.Conclusion: As knowing the receptor status in breast cancer help us as a predictive, prognostic and therapeutic indicator, we must advice it routinely and take steps to make it cheaper and easily available.Chatt Maa Shi Hosp Med Coll J; Vol.16 (2); July 2017; Page 48-50


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