Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients

Rack, Brigitte; Jückstöck, Julia; Günthner-Biller, Maria; Andergassen, Ulrich; J, Neugebauer; Hepp, Philip; Schoberth, A.; Mayr, Doris; Zwingers, Thomas; Scheffold, Christian; Friese, Klaus; Janni, Wolfgang

doi:10.1007/s00404-011-1954-2

Cited by 44 publications

(32 citation statements)

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“…Immunophenotyping changes can be connected to CTCs' and DTCs' intravasation and secondary tissue colonization [39]. Discrepancies in the HER2 status between primary tumor and metastasis have been already described [32,40,41,42,43]. Several studies underlined a discrepancy also between primary tumors and CTCs both in early and metastatic BC patients [44,45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, most DTCs are insensible to common adjuvant chemotherapy regimens, which targets only proliferating tumor cells [35,36]. The validity of HER2-targeted agents on the therapeutic treatment of MRD has been already proposed [24,27,32]. However, in clinical practice, only primary tumor specimens are routinely checked for HER2 status and patients receive anti-HER2-based treatment depending only on these results.…”

Section: Discussionmentioning

confidence: 99%

“…Detection of tumor cells in the cytospin preparation was performed as described previously, using the alkaline phosphatase anti-alkaline phosphatase technique (APAAP; DakoCtyomation, Denmark) [30,31,32]. The murine antibody clone MOPC21 (Sigma, Germany) was used as IgG1 isotype-negative control to test the antibody reaction specificity (data not shown).…”

Section: Methodsmentioning

confidence: 99%

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Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients

et al. 2016

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Objective: The aim of this study was to measure the human epidermal growth factor receptor 2 (HER2) status of disseminated tumor cells (DTCs) from bone marrow (BM) aspirates and to assess correspondence or discrepancy with the primary tumor. Methods: DTCs were isolated from the BM of 156 breast cancer patients. Cytokeratin-positive DTCs were further analyzed by the chromogenic in situ hybridization method to detect HER2 gene amplification. Results: A significant correlation (p = 0.021) was found between the HER2 status of DTCs and the primary tumors. Sixty-one (68.5%) patients had a corresponding status. However, a shift of phenotype between primary tumor and DTCs was found in the remaining patients. Conclusion: This study showed a significant grade of discordance of the HER2 status between primary tumors and DTCs in the BM of a relevant subgroup of patients. Detection of HER2 amplification on DTCs could therefore help to better stratify patients for a more tailored therapy, since they would benefit from a HER2-targeted therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients

et al. 2016

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“…4 Recently, Rack et al presented results of an interventional post-adjuvant trastuzumab-based pilot trial. 69 Ten recurrence-free asymptomatic breast cancer patients with persistent HER2-positive DTC received trastuzumab once every 3 weeks for 12 months. All patients completed chemotherapy at least 6 months prior to entering the study.…”

Section: Targeting Signal Transductionmentioning

confidence: 99%

Dormancy in breast cancer

Banys

Hartkopf

Krawczyk

et al. 2012

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Tumor dormancy describes a prolonged quiescent state in which tumor cells are present, but disease progression is not yet clinically apparent. Breast cancer is especially known for long asymptomatic periods, up to 25 years, with no evidence of the disease, followed by a relapse. Factors that determine the cell's decision to enter a dormant state and that control its duration remain unclear. In recent years, considerable progress has been made in understanding how tumor cells circulating in the blood interact and extravasate into secondary sites and which factors might determine whether these cells survive, remain dormant, or become macrometastases. The mechanisms of tumor cell dormancy are still not clear. Two different hypotheses are currently discussed: tumor cells persist either by completely withdrawing from the cell cycle or by continuing to proliferate at a slow rate that is counterbalanced by cell death. Because dormant disseminated tumor cells may be the founders of metastasis, one hypothesis is that dormant tumor cells, or at least a fraction of them, share stem cell-like characteristics that may be responsible for their long half-lives and their suggested resistance to standard chemotherapy. Therefore, knowledge of the biology of tumor cell dormancy may be the basis from which to develop innovative targeted therapies to control or eliminate this tumor cell fraction. In this review, we discuss biological mechanisms and clinical implications of tumor dormancy in breast cancer patients.

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“…Since CTCs in MBC possibly most adequately represent the current dominant clone of tumor cells, their expression profile may predict therapeutic response [20]. It has been demonstrated in small experimental trials that targeted therapy guided by the CTC phenotype is able to eliminate persistent tumor cells from the blood and/or bone marrow of breast cancer patients [21,22,23]. The clinical significance of the CTC phenotype (in particular, the HER2 status) for guiding therapeutic decisions and evaluating treatment response is being investigated within the DETECT studies.…”

Section: Ctcs As a Prognostic And Predictive Tool In Mbcmentioning

confidence: 99%

Liquid Biopsy in Metastasized Breast Cancer as Basis for Treatment Decisions

et al. 2016

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According to current guidelines, the additional biopsy of breast cancer metastases to analyze the receptor status for phenotype assessment is recommended. However, due to clinical difficulties in performing biopsies of metastatic lesions, the phenotype of the primary tumor most often determines the treatment decisions in metastatic breast cancer. Liquid biopsy allows the analysis of several circulating biomarkers like circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) in peripheral blood samples of cancer patients. Thus, it is an elegant and easily practicable technique that delivers information on the current disease status. Determination of the CTC phenotype regarding the hormone receptor and human epidermal growth factor receptor 2 (HER2) status might replace additional tissue biopsy for planning further therapy strategies. Liquid biopsy is a crucial step towards a more individualized cancer therapy. In contrast to the conventional concept of tissue biopsy, it offers an easy, less invasive acquisition of biomaterial. In addition, it allows multiple repetitions and real-time monitoring of metastasized disease in the clinical routine. However, the clinical utility of liquid biopsy still needs to be evaluated.

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Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients

Cited by 44 publications

References 31 publications

Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients

Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients

Dormancy in breast cancer

Liquid Biopsy in Metastasized Breast Cancer as Basis for Treatment Decisions

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