HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

Wilking, Ulla; Karlsson, Emelié; Skoog, Lambert; Hatschek, Thomas; Lidbrink, Elisabet; Elmberger, Göran; Johansson, Hemming; Lindström, Linda S.; Bergh, Jonas

doi:10.1007/s10549-010-1029-2

Cited by 104 publications

(78 citation statements)

References 28 publications

(36 reference statements)

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“…The power of our study to detect such differences was, however, low. Poor survival associated with receptor discordance in retrospective studies [9][10][11] may be due to inappropriate use of targeted therapy in discordant cases. Biopsy of metastatic lesions may predict sensitivity to endocrine therapy: women with ER-positive and PgR-positive primaries, who were treated with endocrine therapy after their biopsy, had a higher likelihood of being progression-free at 12 months if PgR was maintained in the metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…8 Retrospective analyses of primary and recurrent breast cancers suggest that receptor discordance is associated with poorer survival, [9][10][11] perhaps as a result of the use of inappropriate targeted therapy or the selection of tumors with a more unstable phenotype and therefore more aggressive behavior.…”

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R T V Omentioning

confidence: 99%

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

Amir

Miller

Geddie

et al. 2012

JCO

383

328

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A B S T R A C T PurposeDecisions 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 MethodsBiopsies 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. ResultsOf 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. ConclusionBiopsy 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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Section: Discussionmentioning

confidence: 99%

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R T V Omentioning

confidence: 99%

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

Amir

Miller

Geddie

et al. 2012

JCO

383

328

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“…Today, assessment of HER2 status is based on tumor biopsy. However, HER2 expression can vary between the primary tumor and metastases in up to 40% of cases (2,5,6) and metastatic HER2 expression can change over time, which could necessitate a change of therapy (7,8). Follow-up using biopsies cannot always be performed due to practical reasons or patient discomfort.…”

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confidence: 99%

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

et al. 2016

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68 Ga-ABY-025 is a radiolabeled Affibody molecule for in vivo diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors with PET. The aim of the present work was to measure the biodistribution and estimate the radiation dosimetry of 68 Ga-ABY-025 for 2 different peptide mass doses in a single group of patients using dynamic and serial whole-body PET/CT. Methods: Eight patients with metastatic breast cancer were included. Each patient underwent an abdominal 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 4 h after injection of a low peptide dose (LD) and a high peptide dose (HD), with approximately the same amount of radioactivity, in separate investigations 1 wk apart. As input to the absorbed dose calculations, volumes of interest were drawn on all clearly identifiable source organs: liver, kidneys, spleen, descending aorta, and upper large intestine. Absorbed doses were calculated using OLINDA/EXM, version 1.1. Results: Of the major organs, the highest radionuclide uptake at 1, 2, and 4 h after injection was observed in the kidneys and liver. The highest absorbed organ doses were seen in the kidneys, followed by the liver for both LD and HD 68 Ga-ABY-025. Absorbed doses to liver and kidneys were slightly but significantly higher for LD. Total effective dose was 0.030 ± 0.003 mSv/MBq for LD and 0.028 ± 0.002 mSv/MBq for HD. Conclusion: The effective dose for a typical 200-MBq administration of 68 Ga-ABY-025 is 6.0 mSv for LD and 5.6 mSv for HD. Therefore, from a radiation dosimetry point of view, HD is preferred for PET/CT evaluation of HER2-expressing breast cancer tumors. These effective doses are somewhat higher than earlier published values for other 68 Ga-labeled tracers, such as 0.021 ± 0.003 mSv/MBq for 68 Ga-DOTATATE and 68 Ga-DOTATOC, mainly because of higher uptake in liver and kidney. Forwomen,br east cancer is currently the most common cancer.Human epidermal growth factor receptor 2 (HER2) is overexpressed in about 1 of 6 cases (1-3) at initial diagnosis and is associated with poor survival (1,3). Treatments targeted to HER2, such as with the anti-HER2 antibody trastuzumab, have considerably improved overall survival (1,3,4). Today, assessment of HER2 status is based on tumor biopsy. However, HER2 expression can vary between the primary tumor and metastases in up to 40% of cases (2,5,6) and metastatic HER2 expression can change over time, which could necessitate a change of therapy (7,8). Follow-up using biopsies cannot always be performed due to practical reasons or patient discomfort.Molecular imaging using SPECT and PET might be a noninvasive, whole-body-based way to evaluate HER2 expression quantitatively. One such approach is the use of trastuzumab labeled with 111 In (half-time, 2.8 d) (9) or 89 Zr (3.3 d) (10) for use with SPECT and PET, respectively, but the slow kinetics of antibodies require imaging several days after administration. One promising method of fast, safe, and accurate imaging that specifically binds to a site on the receptor not occu...

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“…Immunohistochemical reactivity of tumor cells to ER, PR, and HER-2/neu helps the clinician to establish the mode of therapy and indicates the survival and recurrence rates of the tumor. The recurred tumor or metastatic tumor may not show the same immunoreactivity, and the unstable status of HER-2/neu in breast cancer is clinically significant [3] . Receptor status in recurred or metastasized breast cancer can be different from the original tumor.…”

Section: Original Articlementioning

confidence: 99%

Automation of immunohistochemical evaluation in breast cancer using image analysis

Prasad

Tiwari²,

Ilanthodi³

et al. 2011

WJCO

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AIM:To automate breast cancer diagnosis and to study the inter-observer and intra-observer variations in the manual evaluations. METHODS:Breast tissue specimens from sixty cases were stained separately for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2/neu). All cases were assessed by manual grading as well as image analysis. The manual grading was performed by an experienced expert pathologist. To study inter-observer and intra-observer variations, we obtained readings from another pathologist as the second observer from a different laboratory who has a little less experience than the first observer. We also took a second reading from the second observer to study intra-observer variations. Image analysis was carried out using in-house developed software (TissueQuant). A comparison of the results from image analysis and manual scoring of ER, PR and HER-2/neu was also carried out. RESULTS:The performance of the automated analysis in the case of ER, PR and HER-2/neu expressions was compared with the manual evaluations. The performance of the automated system was found to correlate well with the manual evaluations. The inter-observer variations were measured using Spearman correlation coefficient r and 95% confidence interval. In the case of ER expression, Spearman correlation r = 0.53, in the case of PR expression, r = 0.63, and in the case of HER-2/neu expression, r = 0.68. Similarly, intra-observer variations were also measured. In the case of ER, PR and HER-2/ neu expressions, r = 0.46, 0.66 and 0.70, respectively. CONCLUSION:The automation of breast cancer diagnosis from immunohistochemically stained specimens is very useful for providing objective and repeatable evaluations.

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HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

Cited by 104 publications

References 28 publications

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

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

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients

Automation of immunohistochemical evaluation in breast cancer using image analysis

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HER2 status in a population-derived breast cancer cohort: discordances during tumor progression

Cited by 104 publications

References 28 publications

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

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

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients

Automation of immunohistochemical evaluation in breast cancer using image analysis

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Product

Resources

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Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule ⁶⁸Ga-ABY-025 in Breast Cancer Patients