International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

Cardoso, Fátima; Bedard, Philippe L.; Winer, Eric P.; Pagani, Olivia; Senkus, Elżbieta; Fallowfield, Lesley; Kyriakides, S.; Costa, Alberto; Čufer, Tanja; Albain, Kathy S.

doi:10.1093/jnci/djp235

Cited by 212 publications

(142 citation statements)

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“…Cells (4x10 3 ) were seeded in 96-well plates and treated with 25 nM LBH589 for 24 h. After treatment, cells were fixed in PFA 1% and incubated with polyclonal anti-E-cadherin antibody (1:100 dilution, Sigma) at 4˚C overnight. Then cells were washed with PBS containing 0.5% Triton and 0.05% NaN 3 followed by detection with antirabbit Cy3-conjugated secondary antibody (1:1,000 dilution, GE Healthcare Europe, GmbH, Milan, Italy) in PBS plus 0.5% Triton and 0.05% NaN 3 for 2 h. Nuclear staining was obtained by treating cells with Hoechst 33258 (500 ng/ml in DMSO) in PBS.…”

Section: Methodsmentioning

confidence: 99%

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The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype

Fortunati

Marano

Bandino

et al. 2013

International Journal of Oncology

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Abstract. Triple-negative breast cancer (TNBC) is a very aggressive type of tumour and its aggressiveness is linked to E-cadherin downregulation. In estrogen-sensitive breast cancer, high levels of E-cadherin fit with high levels of ERα and MTA3 (a component of the transcription Mi-2/NuRD complex with intrinsic DAC activity). In TNBC the E-cadherin downregulation could be due to epigenetic silencing of the CDH1 gene as well as to the lack of a fully functioning ERα-activated pathway. We report that the pan-histone deacetylase inhibitor LBH589, a potent anti-proliferative agent, induced E-cadherin expression on cell membranes of MDA-MB-231 cells (TNBC), determining a reduction of cell invasion and migration. Even though E-cadherin expression in breast cancer is also regulated by estradiol and the ERα/MTA3/Snail/Slug pathway, LBH589 is able to increase E-cadherin without affecting the estrogen pathway. In fact, no expression of ERα, PR and FoxA1 was observed in MDA-MB-231 cells before and after LBH589 treatment; furthermore, the drug caused an increase in Snail and Slug expression with a concomitant reduction of MTA3 levels. Taking into consideration its anti-proliferative and anti-invasive properties, we suggest the use of LBH589 in aggressive breast cancer refractory to hormonal therapy. IntroductionBreast cancer, the most common cancer in women all over the world (1), is generally managed with success thank to available treatments (2). Regrettably, resistance to conventional therapy and increasing in metastatic and aggressive disease are emerging problems (3,4). A particular aggressive subtype of breast cancer is the triple-negative breast cancer (TNBC) that is defined by the absence of ER, PR and Her2/neu (5,6). TNBC generally occurs more frequently in younger women, frequently presents early metastatic spread and has poor overall prognosis (7,8).In breast cancer, as well as in other tumour types, epigenetic modifications are considered a crucial mechanism involved in cancer growth, dedifferentiation and aggressiveness; indeed, epigenetic deregulation can alter a number of molecular pathways involved in the control of cell function. Epigenetic drugs, able to restore normal epigenome in cancer cells, are under extensive pharmacological research (9). In breast cancer, histone acetylation state is considered of great importance. Histone acetylation and deacetylation, controlled by the enzymes histone acetyltransferases (HATs) and histone deacetylases (HDACs), affect chromatin conformation and, therefore, gene transcription, DNA repair and replication, and cell cycle checkpoints (10). Altered expression of HDACs has been reported in breast cancer by several authors (11,12). Therefore, HDAC inhibitors (DCI) are considered valuable therapeutic tools and have been under extensive evaluation. DCI vorinostat (13), for example, in association with paclitaxel and bevacizumab induced a partial or complete response in >50% of patients with metastatic breast cancer. The antiproliferative and re-differentiating effect of sev...

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Section: Methodsmentioning

confidence: 99%

“…Regrettably, resistance to conventional therapy and increasing in metastatic and aggressive disease are emerging problems (3,4). A particular aggressive subtype of breast cancer is the triple-negative breast cancer (TNBC) that is defined by the absence of ER, PR and Her2/neu (5,6).…”

Section: Introductionmentioning

confidence: 99%

The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype

Fortunati

Marano

Bandino

et al. 2013

International Journal of Oncology

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“…Even though its management has become more and more successful over time, owing to the different available therapeutic strategies [2], both metastatic disease and cancer which are becoming resistant to conventional treatment are emerging problems [3,4]. New drugs with anti-tumour activity and/or able to modify the expression of selected molecules in these situations are under evaluation.…”

Section: Introductionmentioning

confidence: 99%

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Fortunati

Catalano

Marano

et al. 2010

Breast Cancer Res Treat

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International audienceNew drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease

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“…Комбинации являются более токсичными, чем моно-терапия, и при этом не имеют доказанных преиму-ществ в отношении увеличения общей выживаемости (ОВ), поэтому при мРМЖ рекомендовано последова-тельное назначение монорежимов, по крайней мере начиная со 2-й линии лечения. Так как комбинации обеспечивают большую частоту объективного ответа (ЧОО), эту стратегию следует рассматривать при быс-тром прогрессировании болезни и наличии угрожаю-щих жизни висцеральных метастазов [2][3][4][5][6][7].…”

Section: Abstract: Metastatic Breast Cancer Anthracyclines Pegylatunclassified

Place of pegylated liposomal doxorubicin in the therapy of metastatic breast cancer

Артамонова¹

2016

Tumors of female reproductive system

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35М а м м о л о г и я / M a m m o l o g y 2 ' 2 0 1 6 Том 12 / Vol. 12 ОПУХОЛИ ЖЕНСКОЙ РЕПРОДУКТИВНОЙ СИСТЕМЫ TUMORS OF FEMALE REPRODUCTIVE SYSTEM Key words: metastatic breast cancer, anthracyclines, pegylated liposomal doxorubicinВведение Метастатический рак молочной железы (мРМЖ) продолжает оставаться неизлечимым заболеванием, и лишь небольшая часть пациенток, как правило, с гормонозависимым типом опухоли, может рассчи-тывать на значительную продолжительность жизни от момента выявления диссеминации. Благодаря на-учным достижениям последних 2 десятилетий в арсе-нале онкологов появилось большое число новых ле-карственных агентов, включающих биологические таргетные препараты. Это позволило улучшить конт-роль роста опухоли и увеличить выживаемость, однако в целом наши успехи в лечении мРМЖ можно оценить как незначительные: медиана выживаемости больных составляет на сегодняшний день 24-36 мес и только 24 % живут более 5 лет [1].Кроме увеличения продолжительности жизни важ-нейшей целью является сохранение ее качества, кото-рое может значительно снизиться в результате нежела-тельных явлений на фоне применения цитостатиков. Комбинации являются более токсичными, чем моно-терапия, и при этом не имеют доказанных преиму-ществ в отношении увеличения общей выживаемости (ОВ), поэтому при мРМЖ рекомендовано последова-тельное назначение монорежимов, по крайней мере начиная со 2-й линии лечения. Так как комбинации обеспечивают большую частоту объективного ответа (ЧОО), эту стратегию следует рассматривать при быс-тром прогрессировании болезни и наличии угрожаю-щих жизни висцеральных метастазов [2][3][4][5][6][7].Не менее серьезным является вопрос о том, когда специфическое противоопухолевое лечение должно

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International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy

Cited by 212 publications

References 56 publications

The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype

The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Place of pegylated liposomal doxorubicin in the therapy of metastatic breast cancer

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