Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events

Karlsson, Emelié; Sandelin, Kerstin; Appelgren, Jari; Zhou, Wenjing; Jirström, Karin; Bergh, Jonas; Wärnberg, Fredrik

doi:10.1016/j.ejca.2013.10.020

Cited by 20 publications

(14 citation statements)

References 150 publications

(160 reference statements)

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“…Growing evidence of heterogeneous HER2 expression complicates the clinical decision making, as immunohistochemistry (IHC) or in situ hybridization (ISH) analysis of the primary tumour is unreliable as sole source of information in the metastatic setting [5, 8–11]. Current guidelines recommend biopsy with renewed IHC and/or ISH evaluation from at least one metastasis before decision about further HER2-targeted therapy [12].…”

Section: Introductionmentioning

confidence: 99%

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

Sandberg

Tolmachev

Velikyan

et al. 2017

Eur J Nucl Med Mol Imaging

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PurposeIn phase I/II-studies radiolabelled ABY-025 Affibody molecules identified human epidermal growth factor receptor 2 (HER2) expression in breast cancer metastases using PET and SPECT imaging. Here, we wanted to investigate the utility of a simple intra-image normalization using tumour-to-reference tissue-ratio (T/R) as a HER2 status discrimination strategy to overcome potential issues related to cross-calibration of scanning devices.MethodsTwenty-three women with pre-diagnosed HER2-positive/negative metastasized breast cancer were scanned with [111In]-ABY-025 SPECT/CT (n = 7) or [68Ga]-ABY-025 PET/CT (n = 16). Uptake was measured in all metastases and in normal spleen, lung, liver, muscle, and blood pool. Normal tissue uptake variation and T/R-ratios were established for various time points and for two different doses of injected peptide from a total of 94 whole-body image acquisitions. Immunohistochemistry (IHC) was used to verify HER2 expression in 28 biopsied metastases. T/R-ratios were compared to IHC findings to establish the best reference tissue for each modality and each imaging time-point. The impact of shed HER2 in serum was investigated.ResultsSpleen was the best reference tissue across modalities, followed by blood pool and lung. Spleen-T/R was highly correlated to PET SUV in metastases after 2 h (r = 0.96, P < 0.001) and reached an accuracy of 100% for discriminating IHC HER2-positive and negative metastases at 4 h (PET) and 24 h (SPECT) after injection. In a single case, shed HER2 resulted in intense tracer retention in blood. In the remaining patients shed HER2 was elevated, but without significant impact on ABY-025 biodistribution.ConclusionT/R-ratios using spleen as reference tissue accurately quantify HER2 expression with radiolabelled ABY-025 imaging in breast cancer metastases with SPECT and PET. Tracer binding to shed HER2 in serum might affect quantification in the extreme case.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3650-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

Sandberg

Tolmachev

Velikyan

et al. 2017

Eur J Nucl Med Mol Imaging

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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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“…Although some studies were limited to histopathological and immunohistochemical features without molecular comparison, their results indicated that about 80-90% of recurrences are actually outgrowths from initially incompletely removed DCIS. 71,72 Other studies investigated copy number aberrations and loss of heterozygosity, which resulted in a similar high concordance between primary DCIS lesions and their recurrences. [73][74][75][76] To our opinion, retrospective studies should therefore only focus on these patients who recurred, and not on the entire initial patient cohort (Fig.…”

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confidence: 99%

“…Only few studies have investigated the relationship between primary DCIS lesions and their recurrences. Although some studies were limited to histopathological and immunohistochemical features without molecular comparison, their results indicated that about 80–90% of recurrences are actually outgrowths from initially incompletely removed DCIS . Other studies investigated copy number aberrations and loss of heterozygosity, which resulted in a similar high concordance between primary DCIS lesions and their recurrences .…”

Section: Introductionmentioning

confidence: 99%

“…Although genomic profiling requires larger financial resources, it allows a more refined comparison than mere immunohistochemistry. This is especially important as protein expression profiles (e.g., ER, PR and HER2 status) can change during breast cancer progression . An integrated approach of histopathological and molecular characteristics should enable to distinguish second primary breast lesions from true DCIS outgrowths with a higher degree of certainty than morphological and immunohistochemical features alone, and subsequent analyses can then be continued with the latter.…”

Section: Introductionmentioning

confidence: 99%

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A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

Bockstal

Agahozo

Koppert

et al. 2019

Intl Journal of Cancer

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Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen‐detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast‐conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So‐called “recurrences” are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment.

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Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events

Cited by 20 publications

References 150 publications

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

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

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

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Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events

Cited by 20 publications

References 150 publications

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT

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

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

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