Reliability of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry in Breast Core Needle Biopsies

2010 ◽  
Vol 28 (20) ◽  
pp. 3264-3270 ◽  
Author(s):  
Annette Lebeau ◽  
Andreas Turzynski ◽  
Susanne Braun ◽  
Wera Behrhof ◽  
Barbara Fleige ◽  
...  

Purpose Core needle biopsies (CNBs) are widely used to determine human epidermal growth factor receptor 2 (HER2) status in breast cancer. Recent publications reported up to 20% false-positive results on CNBs if immunohistochemistry (IHC) is compared with fluorescent in situ hybridization (FISH). To clarify, if confirmation of IHC positivity by FISH is generally required, we analyzed the reliability of IHC positivity on CNBs versus surgical specimens in a multi-institutional study. Patients and Methods Five pathologic laboratories contributed to this study by performing IHC on 500 CNBs and the corresponding surgical specimens overall. If IHC revealed score 2+ or 3+, HER2 status was confirmed by FISH in a central laboratory. We compared evaluation according to US Food and Drug Administration–approved scoring criteria and recently published American Society of Clinical Oncology (ASCO)–College of American Pathologists (CAP) guidelines. Results CNBs scored 3+ revealed five false-positive results if scoring followed the US Food and Drug Administration criteria (five of 40; 12.5%) and two false-positives in terms of the ASCO-CAP criteria (two of 33; 6.1%). IHC was false negative in one CNB only. By contrast, IHC on surgical specimens revealed five false-negative results, but only one false-positive result (one of 35; 2.9%) if scored following US Food and Drug Administration–approved criteria. With the aid of the ASCO-CAP criteria, false-positive IHC results were obtained in only one of the five participating institutions. Conclusion IHC 3+ scores on CNBs proved to be reliable in four of the five participating institutions if scoring followed the ASCO-CAP criteria. Therefore, accurate determination of HER2 status in breast cancer is possible on CNB using the common strategy to screen all cases by IHC and retest only 2+ scores by FISH. Prerequisites are quality assurance and the application of the new ASCO-CAP criteria.

PET Clinics ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. 289-298 ◽  
Author(s):  
Rakesh Kumar ◽  
Neerja Rani ◽  
Chetan Patel ◽  
Sandip Basu ◽  
Abass Alavi

2013 ◽  
Vol 31 (21) ◽  
pp. 2692-2698 ◽  
Author(s):  
Ann H. Partridge ◽  
Shari Gelber ◽  
Martine J. Piccart-Gebhart ◽  
Florine Focant ◽  
Matthew Scullion ◽  
...  

Purpose Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial. Patients and Methods We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation. Results Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age ≤ 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age ≤ 40 versus > 40 years, regardless of treatment assignment (observation group: DFS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age ≤ 40 v > 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age ≤ 40 v > 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55). Conclusion In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes.


2017 ◽  
Vol 9 (7) ◽  
pp. 493-511 ◽  
Author(s):  
Karima Oualla ◽  
Heba M. El-Zawahry ◽  
Banu Arun ◽  
James M. Reuben ◽  
Wendy A. Woodward ◽  
...  

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels. The use of biomarkers to identify distinct subsets of TNBC that derive the greatest benefit from presently approved as well as novel therapeutics has become the main focus of current research. The aim of this review is to explore the clinical and biological complexity of TNBC as well as identify novel therapeutic options that target the various molecular subsets of TNBC.


ISRN Oncology ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Christian Garbar ◽  
Aude-Marie Savoye ◽  
Corinne Mascaux ◽  
Eva Brabencova ◽  
Hervé Curé

Aims. The differences between the 2007 and the 2013 ASCO/CAP HER2 guidelines have been compared. We also discussed the potential consequences in our pathological practice. Material and Methodology. 189 HER2 fluorescence in situ hybridisation (FISH) tests were performed from 1016 preliminary HER2 immunohistochemical tests (IHC). All cases were reviewed and reclassed following the 2007 and 2013 ASCO/CAP recommendations. Results. The 2013 version decreased false-negative IHC (3/118 versus 1/54, P=ns) and created more 2+ IHC (40/186 versus 89/186, P=0.001) or more 3+ IHC (9/186 versus 39/186, P=0.001). One false-positive IHC was described for the 2013 version (0/9 versus 1/39, P=ns). Equivocal FISH was reduced (8/186 versus 2/186, P=ns). An estimation based on our data for 1000 patients showed a rise of our FISH tests for the control of 2+ IHC (180 tests for the 2007 version versus 274 tests for the 2013 version or FISH work overflow is +52%) and for the control of 2+/3+ IHC (300 for the 2007 version versus 475 for the 2013 version or FISH work overflow is +58%). Conclusions. The new 2013 ASCO/CAP guidelines have detected more HER2 positive cases but have increased the number of FISH tests.


2012 ◽  
Vol 30 (21) ◽  
pp. 2601-2608 ◽  
Author(s):  
Linda Sofie Lindström ◽  
Eva Karlsson ◽  
Ulla M. Wilking ◽  
Ulla Johansson ◽  
Johan Hartman ◽  
...  

Purpose To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. Patients and Methods The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. Conclusion Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.


2018 ◽  
Vol 154 ◽  
pp. 03016
Author(s):  
Izzati Muhimmah ◽  
Dadang Heksaputra ◽  
Indrayanti

One of the major challenges in the development of early diagnosis to assess HER2 status is recognized in the form of Gold Standard. The accuracy, validity and refraction of the Gold Standard HER2 methods are widely used in laboratory (Perez, et al., 2014). Method determining the status of HER2 (human epidermal growth factor receptor 2) is affected by reproductive problems and not reliable in predicting the benefit from anti-HER2 therapy (Nuciforo, et al., 2016). We extracted color features by methods adopting Statistics-based segmentation using a continuous-scale naïve Bayes approach. In this study, there were three parts of the main groups, namely image acquisition, image segmentation, and image testing. The stages of image acquisition consisted of image data collection and color deconvolution. The stages of image segmentation consisted of color features, classifier training, classifier prediction, and skeletonization. The stages of image testing were image testing, expert validation, and expert validation results. Area segmentation of the membrane is false positive and false negative. False positive and false negative from area are called the area of system failure. The failure of the system can be validated by experts that the results of segmentation region is not membrane HER2 (noise) and the segmentation of the cytoplasm region. The average from 40 data of HER2 score 2+ membrane images show that 75.13% of the area is successfully recognized by the system.


2021 ◽  
Vol 10 (4) ◽  
pp. 866
Author(s):  
Agnė Bartnykaitė ◽  
Aistė Savukaitytė ◽  
Rasa Ugenskienė ◽  
Monika Daukšaitė ◽  
Erika Korobeinikova ◽  
...  

Breast cancer is one of the most common cancers worldwide. Single nucleotide polymorphisms (SNPs) in MDM2 and MDM4 have been associated with various cancers. However, the influence on clinical characteristics of breast cancer has not been sufficiently investigated yet. Thus, this study aimed to investigate the relationship between SNPs in MDM2 (rs2279744, rs937283, rs937282) and MDM4 (rs1380576, rs4245739) and I–II stage breast cancer. For analysis, the genomic DNA was extracted from 100 unrelated women peripheral blood. Polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The study showed that MDM2 rs937283 and rs937282 were significantly associated with estrogen receptor status and human epidermal growth factor receptor 2 (HER2) status. SNPs rs1380576 and rs4245739, located in MDM4, were significantly associated with status of estrogen and progesterone receptors. Our findings suggest that rs937283 AG, rs937282 CG, rs1380576 CC, and rs4245739 AA genotypes were linked to hormonal receptor positive breast cancer and may be useful genetic markers for disease assessment.


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