scholarly journals Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: Experience at tertiary cancer care centre

2017 ◽  
Vol 06 (02) ◽  
pp. 045-046
Author(s):  
Manoj Kumar Panigrahi ◽  
Dushyant Kumar ◽  
Anurag Mehta ◽  
Kandarpa Kumar Saikia
Keyword(s):  
Breast Cancer ◽  
Final Analysis ◽  
Chromosome 17 ◽  
Research Centre ◽  
Her2 Status ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Polysomy 17 ◽  
Cancer Experience ◽  
The Impact

Abstract Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

scholarly journals Rate of reclassification of HER2-equivocal breast cancer cases to HER2-negative per the 2018 ASCO/CAP guidelines and response of HER2-equivocal cases to anti-HER2 therapy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241775
Author(s):  
James Crespo ◽  
Hongxia Sun ◽  
Jimin Wu ◽  
Qing-Qing Ding ◽  
Guilin Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Cancer Center ◽  
Her2 Status ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Primary Disease ◽  
The Impact

Purpose The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer permits reclassification of cases with HER2-equivocal results by FISH. The impact of such reclassification is unclear. We sought to determine the proportion of HER2-equivocal cases that are reclassified as HER2-negative and the impact of anti-HER2 therapy on survival in HER2-equivocal cases. Methods We reviewed medical records of breast cancer patients who had HER2 testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline. The population was divided into 2 cohorts according to whether the biopsy specimen analyzed came from primary or from recurrent or metastatic disease. HER2 status was reclassified according to the 2018 ASCO/CAP guideline. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and the relationship between anti-HER2 therapy and clinical outcomes was assessed. Results We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease. Per the 2018 ASCO/CAP guideline, these cases were classified as follows: overall, HER2-negative 112 cases (80%), HER2-positive 1 (1%), and unknown 26 (19%); primary cohort, HER2-negative 85 (94%), HER2-positive 1 (1%), unknown 4 (4%); and recurrent/metastatic, HER2-negative 27 (55%) and unknown 22 (45%). Five patients in the primary-disease cohort and 1 patient in the recurrent/metastatic-disease cohort received anti-HER2 therapy. There was no significant association between anti-HER2 therapy and OS or EFS in either cohort (primary disease: OS, p = 0.67; EFS, p = 0.49; recurrent/metastatic-disease, OS, p = 0.61; EFS, p = 0.78. Conclusions The majority of HER2-equivocal breast cancer cases were reclassified as HER2-negative per the 2018 ASCO/CAP guideline. No association between anti-HER2 therapy and OS or EFS was observed. HER2-equivocal cases seem to have clinical behavior similar to that of HER2-negative breast cancers.

HER2 status testing by immunohistochemical and fFluorescence in situ hybridization in China

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22233-e22233
Author(s):  
W. Tao ◽  
J. Zefei ◽  
Z. Xuan ◽  
L. Xiaobing ◽  
Z. Shaohua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Her2 Status ◽  
Central Laboratory ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Clinical Prognosis ◽  
Her2 Testing ◽  
Regional Laboratory

e22233 Background: HER2 gene overexpression is associated with aggressive breast cancer and poor clinical prognosis. Humanized anti-HER2 monoclonal antibody trastuzumab, which is targeted HER2 protein has showed to improve overall survival in patients with HER2-positive breast cancer in both the metastatic and adjuvant settings. There are some differences in HER2 positive rate among difference reports in China. This study tested HER2 status by immunohistochemistry(IHC) and fluorescence in situ hybridization (FISH) and compared HER2 testing at central and regional laboratories in China. Methods: Assessment of HER2 status was performed by FISH using the HercepTeast kit at central laboratory and by IHC using commercial available anti-HER2 probe in formalin-fixed and paraffin-embedded tissue section of 280 breast cancer samples. IHC HER2 testing was performed on 149 samples in the central laboratory. IHC HER2 testing was performed on 80 samples at both central laboratory and regional laboratory. Results: 280 samples were tested 373 times testing by IHC and FISH. The results were showed in table 1 . 80 samples was tested by IHC at central and regional laboratory and testing results of 36.4% samples were accordant (K=0.038). 94.1% IHC3+ at central laboratory were HER2 FISH positive and 83.3% IHC 3+ at regional laboratory were HER2 FISH positive. 86.7% IHC 2+ at central laboratory were HER2 FISH positive and 62.7% IHC 2+ at regional laboratory were HER2 FISH positive. 17 samples were observed HER2 FISH positive in the 27 IHC 0/1+ tested at regional laboratoty. So good correlation was obsearved between FISH HER2 status and IHC results from central laboratory but not from regional laboratory. Conclusions: This study emphasized the important of accurate HER2 testing. HER2 FISH test should be performed for the IHC 2+ samples. Even HER2 FISH test maybe performed for IHC 0/1 sample according to clinical characteristics in China in order to make the patients have targeted therapy chance. [Table: see text] No significant financial relationships to disclose.

scholarly journals Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

2017 ◽  
Vol 3 (4) ◽  
pp. 314-322 ◽  
Author(s):  
Ettienne J. Myburgh ◽  
Lizanne Langenhoven ◽  
Kathleen A. Grant ◽  
Lize van der Merwe ◽  
Maritha J. Kotze
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Molecular Subtype ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Luminal A ◽  
Her2 Positive ◽  
Molecular Subtyping ◽  
Predictive Values ◽  
Her2 Positivity

Purpose Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping. Methods Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor–positive and/or progesterone receptor–positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study. Results The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal ( P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors ( P = .0002; 95% CI, 0.40 to 1.06). Conclusion Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value.

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 Biomarkers in Her2- Positive Disease

Breast Care ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. 586-593
Author(s):  
Eva Valentina Klocker ◽  
Christoph Suppan
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
Treatment Decision ◽  
Tumor Infiltrating Lymphocytes ◽  
Micro Rna ◽  
Her2 Status ◽  
Her2 Positive ◽  
Brca Mutations ◽  
Pik3ca Mutations ◽  
The Impact

<b><i>Background:</i></b> Breast cancer is a heterogeneous disease with well-known characteristics such as hormone receptor (HR) status and human epidermal growth factor (Her)2 status. Although Her2 represents an established treatment target, the development of resistance mechanisms during treatment, cardiotoxicity, and a worse response to standard therapies lead to worse outcomes. <b><i>Summary:</i></b> Therefore, we investigated various biomarkers in breast cancer such as Her2 mutations, Her2 heterogeneity, HR, PIK3CA, PTEN, programmed death receptor ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TIL), micro RNA (miRNA), and BRCA mutations with regard to their clinical impact in Her2-positive disease. HR status and Her2 status, such as the presence of PIK3CA mutations, already play a role in treatment decision-making processes, whereas other biomarkers like PD-L1 status or TIL represent promising future markers. The influence of BRCA mutations in Her2-positive disease, Her2 mutations, and the impact of miRNA is vague to date. Antibody-drug conjugates (ADC) such as T-DM have been established as important treatment strategies, especially in Her2-positive disease. <b><i>Key Message:</i></b> However, up-to-date biomarkers appropriate for clinical practice are missing. Further studies are needed.

The impact of screening mammography in women age 40-49 as a function of tumor biology.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 113-113
Author(s):  
John C. Ruckdeschel ◽  
William V. Rees ◽  
Brett T Parkinson ◽  
Thomas Belnap ◽  
Braden D. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Large Scale ◽  
Triple Negative ◽  
Tumor Biology ◽  
Screening Mammography ◽  
Her2 Status ◽  
Screening Mammogram ◽  
Interval Cancers ◽  
Her2 Positive ◽  
The Impact

113 Background: Mammographic screening for women 40-49 years of age remains controversial based on results from earlier large scale, controlled mammography trials. Methods: From 2002-2006, 871 women aged 40-49 were diagnosed with breast cancer at Intermountain. The charts of all patients without a record of a screening mammogram at Intermountain (n= 436) were reviewed to confirm that they had not had a screening mammogram in the prior two years at any facility (Interval Cancers) and their survival was compared to 435 women who had their cancer diagnosed on a screening exam (Screen Detected). All patients were followed for at least 5 years via the tumor registry. Results: Stage distribution for Screen Detected/Interval cancers was 25.3/6.4% stage 0, 36.8/24.8% stage I, 24.6/35.6% stage II, 6.9/20.4% stage III and 0.5/3.4% stage IV. Overall, 67 patients (7.7%) did not have complete staging data. Overall survival was significantly better (p<.0001) for 40-49 year old women with Screen Detected compared to those with Interval cancers. 702 (79.6%) had ER/PR status recorded (83.5% ER/PR positive). Women with DCIS or LCIS did not have tissue sent for markers. 679 patients (76.9%) had HER2 status recorded (78.8% HER2 neg). Of the patients with both HER2 and ER/PR status recorded 10.4% were “triple negative.” Survival following screening mammography was significantly enhanced for women who were ER/PR positive (p<0.0001), HER2 negative (p=0.0065), or HER2 positive (p=0.0013). Survival was not improved by screening mammography for women who were ER/PR negative (p=0.3818) or for women who were triple negative (p=0.416). Conclusions: A minority of women age 40-49 who develop breast cancer (13%) have biologic features suggestive of aggressive disease and, after 5 years of follow up, they are not benefitted by screening mammography. The remaining 87% are clearly benefitted by screening mammography. Our results suggest that the discrepancies noted in the screening mammography trials in 40-49 year old women may have resulted from population variations in the proportion of women with unfavorable biology. Based in part on these results, we continue to recommend regular screening in the 40-49 year old cohort.

scholarly journals HER2 Testing in Breast Cancer: NCCN Task Force Report and Recommendations

2006 ◽  
Vol 4 (S3) ◽  
pp. S-1-S-22 ◽  
Author(s):  
Robert W. Carlson ◽  
Susan J. Moench ◽  
M. Elizabeth H. Hammond ◽  
Edith A. Perez ◽  
Harold J. Burstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Predictive Factor ◽  
Task Force ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Her2 Expression ◽  
Her2 Testing ◽  
Gene Copies ◽  
Or Gene

The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/ assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed. (JNCCN 2006;4(Suppl 3):S1–S22)

scholarly journals Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Ishimine ◽  
Akira Goto ◽  
Yoshito Watanabe ◽  
Hidetaka Yajima ◽  
Suguru Nakagaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Residual Tumor ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Curative Intent ◽  
Course Of Disease ◽  
Trastuzumab Therapy ◽  
Her2 Positivity

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

HER2 status in early breast cancer: Relevance of cell staining patterns, gene amplification and polysomy 17

2007 ◽  
Vol 43 (16) ◽  
pp. 2339-2344 ◽  
Author(s):  
Rosalba Torrisi ◽  
Nicole Rotmensz ◽  
Vincenzo Bagnardi ◽  
Giuseppe Viale ◽  
Barbara Del Curto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Early Breast Cancer ◽  
Her2 Status ◽  
Polysomy 17 ◽  
Cell Staining

scholarly journals Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 587-592 ◽  
Author(s):  
Eitan Amir ◽  
Naomi Miller ◽  
William Geddie ◽  
Orit Freedman ◽  
Farrah Kassam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Treatment Plan ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Primary Tumors ◽  
Receptor Status ◽  
Metastatic Recurrence ◽  
The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

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