Metastatic breast cancer with liver metastases: a registry analysis of clinicopathologic, management and outcome characteristics of 500 women

Pentheroudakis, George; Fountzilas, George; Bafaloukos, Dimitrios; Koutsoukou, Vasiliki; Pectasides, Dimitrios; Skarlos, Dimosthenis; Samantas, E.; Kalofonos, Haralabos P.; Gogas, Helen; Pavlidis, Nicholas

doi:10.1007/s10549-005-9117-4

Cited by 104 publications

(85 citation statements)

References 11 publications

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“…This finding corroborates results from other studies (5,9). There is great interest in evaluating local treatment options such as surgery or stereotactic radiotherapy in patients with oligo-metastases in the liver but randomized studies are needed to evaluate the efficacy of these treatment options.…”

Section: Discussionsupporting

confidence: 89%

“…However, some studies suggest that patients with liver-only metastatic disease may experience longer survival compared with patients harboring liver metastases in parallel with metastases in other organs (5,9). We found a similar trend in this cohort [ Fig.…”

Section: Liver-only Relapse Is Associated With a Relatively Better Ousupporting

confidence: 76%

“…After diagnosing metastatic breast cancer (MBC), the site of recurrence is an important feature for estimating the patient's prognosis. Liver metastasis is associated with the poorest survival relative to locoregional, bone, and lung colonization (2)(3)(4)(5)(6)(7). Noteworthy, the diagnosis of liver metastases is on the rise (8,9), suggesting that available adjuvant therapies may have limited efficacy in preventing liver colonization compared with metastases at other sites.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Kimbung

Johansson

Danielsson

et al. 2016

Clinical Cancer Research

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in collaboration with the TEX study group Abstract Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis.Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n ¼ 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested.Results: Liver relapse was associated with estrogen receptor (ER) expression (P ¼ 0.002), luminal B subtype (P ¼ 0.01), and was prognostic for an inferior postrelapse survival (P ¼ 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P ¼ 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P ¼ 0.001) among luminal A tumors.Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.

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Section: Discussionsupporting

confidence: 89%

Section: Liver-only Relapse Is Associated With a Relatively Better Ousupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

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Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Kimbung

Johansson

Danielsson

et al. 2016

Clinical Cancer Research

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“…Breast cancer cells preferentially metastasize to specific organs and tissues, with the liver representing the third most frequent site following bone and lung (Clark et al, 1987;Insa et al, 1999). Breast cancer patients with liver metastases display a poor prognosis, with median survival times between 14 and 20 months and 5-year survival rates that reach only 5.5-8.5% (Pentheroudakis et al, 2005;Eichbaum et al, 2006). However, little is known about the molecular mechanisms governing the spread and growth of breast cancer cells in the liver.…”

Section: Introductionmentioning

confidence: 99%

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

et al. 2010

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The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of a 2 b 1 -and a 5 b 1 -integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target a 5 b 1 and a 2 b 1 complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.

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“…The number of non-local recurrent lesions (40% of total recurrences) confirms that metastatic BC is a disease which should be addressed in a multidisciplinary context in which the role of chemotherapy is indisputable [4]. There is an increase in survival of selected patients receiving combined systemic and local therapy [9] compared with survival of patients treated with chemotherapy alone [2]. These results, as well as those related to surgical series [5,6], show that local treatment of metastases from BC may increase survival in selected patients with liver or lung metastases from BC.…”

Section: Discussionmentioning

confidence: 98%

Radiofrequency ablation of metastatic lesions from breast cancer

Bortolotto

Macchi

Veronese

et al. 2012

Journal of Ultrasound

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KEYWORDSBreast carcinoma; Liver metastases; Pulmonary metastases; Radiofrequency ablation.Abstract Introduction: Breast cancer (BC) is the most common malignancy in women. Various studies [5,6] have shown that surgical resection of single liver or lung metastases in patients with metastases from BC increases survival. Radiofrequency ablation (RFA) can be an alternative to resection in some patients when resection is not feasible. Materials and methods: From January 2002 to December 2008, 491 patients with liver metastases underwent US-guided percutaneous RFA. Of these patients 5 (5/491; 1%) had BC. In the same period, 32 patients with pulmonary metastases underwent CT-guided RFA. Of these patients 3 (3/32; 9%) had BC. Mean age was 61.3 years. All patients were postmenopausal and receiving polychemotherapy according to international guidelines. Inclusion criteria for RFA treatment of metastases from BC applied are identical or in some cases more restrictive than those reported in the literature. Results: There were no deaths or severe complications and no treatment failures. Disease free and overall median survival were respectively 7.65 and 25.7 months after US-guided RFA and 13.4 and 34.8 months after CT-guided RFA. During follow-up (mean follow-up 26 months, range 4e63 months) 5/8 (62.5%) patients exhibited recurrence: 3/5 (60%) had local recurrence and 2/5 (40%) had non-local recurrence; 4/5 patients with recurrence were re-treated. Discussion: The authors' experience confirms that RFA is an effective, safe and repeatable technique in the treatment of metastases from BC. Metastatic recurrence rate confirms that metastatic BC is a disease which requires a multidisciplinary approach and that the role of chemotherapy is indisputable. Effects on survival are promising but further confirmation is needed through prospective randomized studies.Sommario Introduzione: Il carcinoma della mammella (BC) è la più frequente neoplasia nel sesso femminile. Vari studi hanno dimostrato che la resezione chirurgica delle MTS epatiche o polmonari singole determina un allungamento della sopravvivenza. La termoablazione a radiofrequenze (RFA) potrebbe rappresentare una valida alternativa alla resezione quando la prima non è fattibile. Materiali e metodi: Presso il nostro centro nel periodo compreso tra gennaio 2002 e dicembre 2008 sono stati trattati con RFA percutanea US-guidata 491 pazienti affetti da MTS epatiche di cui 5 (5/491; 1%) da BC. Nello stesso periodo sono stati trattati con RFA CT-guidata 32 pazienti con MTS polmonari: 3 (3/32; 9%) da BC. L'età media delle pazienti era di 61,3 anni. Tutte le pazienti erano in fase post-menopausale e in trattamento polichemioterapico in accordo con le linee guida internazionali. Le indicazioni per il trattamento delle metastasi da BC utilizzate nel nostro centro sono sovrapponibili o in alcuni casi maggiormente restrittive rispetto a quelle presenti in letteratura. Risultati: Non si sono verificati decessi o complicanze gravi. Non ci sono stati fallimenti terapeutici. La median surviva...

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Metastatic breast cancer with liver metastases: a registry analysis of clinicopathologic, management and outcome characteristics of 500 women

Cited by 104 publications

References 11 publications

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis–Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes

Radiofrequency ablation of metastatic lesions from breast cancer

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