ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients

Fehm, Tanja; Krawczyk, Natalia; Solomayer, Erich‐Franz; Becker-Pergola, Graziella; Dürr-Störzer, S.; Neubauer, Hans; Seeger, Harald; Staebler, Annette; Wallwiener, D.; Becker, Sven

doi:10.1186/bcr2143

Cited by 86 publications

(82 citation statements)

References 34 publications

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“…Although chemotherapy targets highly proliferative cells, dormant tumor cells are mostly either slowly proliferating or in a state of arrested growth. In patients with ER-positive primary tumors with tumor cell spread into their bone marrow, only 14% had ER-positive disseminated tumor cells [26]. This lower ER positivity may cause a low response to endocrine therapy in some cases.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Nishimura¹,

Osako²,

Nishiyama³

et al. 2013

Oncology

9,354

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Background: Breast cancer is associated with a relatively good prognosis. Prognostic factors examined to date are related to early recurrence while those related to late recurrence and their countermeasures remain unclear. Therefore, we examined the factors related to late recurrence. Patients and Methods: From January 1980 to August 2012, 4,774 patients who underwent primary treatment and estrogen (ER) and progesterone receptor (PgR) assessment were enrolled in this study. The patients were divided into two groups, those with a follow-up period <10 years and those without any recurrence at 10 years but who continued follow-up examinations. Recurrence occurred in 711 patients followed up for <10 years and in 51 patients for ≥10 years. Results: The overall 10-year cumulative disease-free survival rate was 79.5%, and the recurrence rate at ≥10 years was 5.8%. A multivariate analysis revealed that the factors related to late recurrence were PgR positivity and positive nodes. This result differed from that for early recurrence in terms of ER/PgR, Ki-67 index and p53 overexpression. Conclusion: PgR positivity and lymph node metastases significantly correlated with late recurrence. Therefore, it is important to evaluate appropriate measures such as treatment period and treatment regimen for hormone-sensitive patients.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Nishimura¹,

Osako²,

Nishiyama³

et al. 2013

Oncology

9,354

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show abstract

“…In a cohort of 88 patients with ER-positive primary tumors who presented with DTC in their bone marrow, only 14% had ER-positive DTC. 65 The loss of ER-positivity in DTC or CTC may explain the failure of endocrine therapy in a subset of ER-positive patients. Therefore, determining the phenotype of MRD is becoming increasingly important, as DTC and CTC are the targets of all adjuvant therapies.…”

Section: Targeting Signal Transductionmentioning

confidence: 99%

“…We and others previously reported a discrepancy between cancer cells from the primary tumor and those in secondary sites, such as blood and bone marrow, especially with regard to HER2 and ER status. 15,[62][63][64][65] HER2 gene amplification can be acquired during disease progression, even if the primary tumor was HER2-negative at the beginning of treatment. 66 However, patients with HER2-negative tumors but HER2-positive MRD are not eligible for HER2-based treatment.…”

Section: Targeting Signal Transductionmentioning

confidence: 99%

Dormancy in breast cancer

Banys

Hartkopf

Krawczyk

et al. 2012

BCTT

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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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“…Repeated invasive biopsies are unacceptable. There is considerable evidence that CTCs/DTCs (2,3,(8)(9)(10) are an effective means for following genetic changes that accompany cancer progression. Our previous studies (11,12) showed that protein expression levels and gene amplification of HER2 could change throughout disease progression and HER2 and uPAR overexpression and gene amplification are correlated by analysis of gene status and expression in CTCs.…”

Section: Introductionmentioning

confidence: 99%

“…In these studies we subjectively quantified gene expression levels of individual CTCs into 1-3 categories after immunofluorescence (IF) staining. In other studies IF staining or/and immunohistochemistry (8,10,13) was used for evaluating positivity for HER2, oestrogen-receptor (ER) or other tumor markers. HER2 testing in CTCs may have clinical relevance for HER2-targeted therapy as HER2-positive CTCs and DTCs can be detected in patients with HER2-negative primary tumors who currently do not have access to HER2-targeted therapy (e.g.…”

Section: Introductionmentioning

confidence: 99%

Quantitative determination of HER2 expression by confocal microscopy assay in CTCs of breast cancer

Cao

Yang²,

Li³

et al. 2009

Oncol Rep

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Abstract. HER2 analysis in circulating tumor cells (CTCs) may have clinical significance for HER2-targeted therapy as HER2-positive CTCs and disseminated tumor cells can be detected in patients with HER2-negative primary tumors who currently do not have access to HER2-targeted therapy. In this study, we performed quantitative analysis by confocal microscopy assay for evaluation of HER2 expression in individual tumor cells. HER2 testing by confocal microscopy assay exhibited high concordance with results of real-time PCR, Western blot analysis and FISH analysis. We found that there was a significant positive correlation between HER2 overexpression and gene amplification in individual CTCs, which provided validation of confocal microscopy assay for HER2 expression in CTCs. By using subsets of 10 consecutive cells (bins), we conclude that HER2 expression (3+) in CTCs predicts HER2 overexpression of tumor with high probability in breast cancer patients. These results may provide interpretive guidelines for HER2 status assay in CTCs and raise great opportunities for using CTCs as non-invasive and 'real-time' biopsy to examine and monitor the status of tumor markers.

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ERalpha-status of disseminated tumour cells in bone marrow of primary breast cancer patients

Cited by 86 publications

References 34 publications

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Dormancy in breast cancer

Quantitative determination of HER2 expression by confocal microscopy assay in CTCs of breast cancer

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