References of "Jerusalem, Guy"
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See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2014, May 19)

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See detailExtended adjuvant endocrine therapy. Who benefits ? For how long ?
JERUSALEM, Guy ULg

Conference (2014, April 24)

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See detailNew chemotherapy drugs in metastatic breast cancer
JERUSALEM, Guy ULg

Conference (2014, February 22)

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See detailStudy of the pro-tumoral effects of MT4-MMP
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2014, January 27)

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See detailVieillissement et cancer: coincidence ou relation etiologique?
Duray, A.; Demoulin, Stéphanie ULg; Petermans, Jean ULg et al

in Revue medicale de Liege (2014), 69(5-6), 276-81

In Belgium and in other countries, the Cancer Registry data show an increased incidence of cancers related to age, the majority of tumors being diagnosed beyond 60 years. However, the mechanisms ... [more ▼]

In Belgium and in other countries, the Cancer Registry data show an increased incidence of cancers related to age, the majority of tumors being diagnosed beyond 60 years. However, the mechanisms responsible for this increase are not clear. Cancer could be chronologically associated with aging because of the long latency period between the exposition to carcinogenic agents and the appearance of clinical signs. Aging could also predispose directly to cancer by different mechanisms (impaired immune response, increased oxidative stress, shortening of telomeres, accumulation of senescent cells). In this review, we propose to describe different hypotheses which could explain the increased incidence of cancers in the elderly. [less ▲]

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See detailExpert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
Plana, Juan Carlos; Galderisi, Maurizio; Barac, Ana et al

in Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography (2014), 27(9), 911-39

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See detailExpert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
Plana, Juan Carlos; Galderisi, Maurizio; Barac, Ana et al

in European heart journal cardiovascular Imaging (2014), 15(10), 1063-93

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See detailL'âgisme et ses conséquences cliniques en oncogériatrie: état des lieux et pistes d'interventions
Schroyen, Sarah ULg; Adam, Stéphane ULg; Jerusalem, Guy ULg et al

in Revue Médicale de Liège (2014), 69(5-6), 395-401

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See detailPhase Ib study of Buparlisib plus Trastuzumab in patients with HER2-positive advanced or metastatic breast cancer that has progressed on Trastuzumab-based therapy.
Saura, Cristina; Bendell, Johanna; Jerusalem, Guy ULg et al

in Clinical cancer research : an official journal of the American Association for Cancer Research (2014), 20(7), 1935-45

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose ... [more ▼]

PURPOSE: Phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway activation in patients with HER2-positive (HER2(+)) breast cancer has been implicated in de novo and acquired trastuzumab resistance. The purpose of this study was to determine the clinical activity of the PI3K inhibitor buparlisib (BKM120) in patients with HER2(+) advanced/metastatic breast cancer resistant to trastuzumab-based therapy. EXPERIMENTAL DESIGN: In the dose-escalation portion of this phase I/II study, patients with trastuzumab-resistant locally advanced or metastatic HER2(+) breast cancer were treated with daily oral doses of buparlisib and weekly intravenous trastuzumab (2 mg/kg). Dose escalation was guided by a Bayesian logistic regression model with overdose control. RESULTS: Of 18 enrolled patients, 17 received buparlisib. One dose-limiting toxicity of grade 3 general weakness was reported at the 100-mg/day dose level (the single-agent maximum tolerated dose) and this dose level was declared the recommended phase II dose (RP2D) of buparlisib in combination with trastuzumab. Common (>25%) adverse events included rash (39%), hyperglycemia (33%), and diarrhea (28%). The pharmacokinetic profile of buparlisib was not affected by its combination with trastuzumab. At the RP2D, there were two (17%) partial responses, 7 (58%) patients had stable disease (>/=6 weeks), and the disease control rate was 75%. Pharmacodynamic studies showed inhibition of the PI3K/AKT/mTOR and RAS/MEK/ERK pathways. CONCLUSIONS: In this patient population, the combination of buparlisib and trastuzumab was well tolerated, and preliminary signs of clinical activity were observed. The phase II portion of this study will further explore the safety and efficacy of this combination at the RP2D. Clin Cancer Res; 20(7); 1935-45. (c)2014 AACR. [less ▲]

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See detailNeoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.
Bonnefoi, H.; Jacot, W.; Saghatchian, M. et al

in Annals of oncology : official journal of the European Society for Medical Oncology / ESMO (2014)

BACKGROUND: Neoadjuvant trials conducted using a double HER2-blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological ... [more ▼]

BACKGROUND: Neoadjuvant trials conducted using a double HER2-blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1:1:1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab+lapatinib at the same dose. The primary endpoint was pCR rate defined as ypT0/is. Secondary endpoints included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 evaluable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib+trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib+trastuzumab arms were: febrile neutropenia 23/15/10, diarrhea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. This study is registered with ClinicalTrials.gov, number NCT00450892. [less ▲]

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See detailA new era of improving progression-free survival with dual blockade in postmenopausal HR, HER2 advanced breast cancer.
Jerusalem, Guy ULg; Bachelot, Thomas; Barrios, Carlos et al

in Cancer treatment reviews (2014)

Disease progression despite existing endocrine therapies remains a major challenge to the effective management of hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2 ... [more ▼]

Disease progression despite existing endocrine therapies remains a major challenge to the effective management of hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-), advanced breast cancer. Recent advances in elucidating the molecular mechanisms of disease progression have identified the existence of adaptive "cross-talk" between the estrogen receptor (ER) and various growth factor receptor and intracellular signaling pathways, allowing breast cancer cells to escape the inhibitory effects of endocrine therapy. These findings provide the clinical rationale for enhancing or extending endocrine sensitivity by combining endocrine therapy with a targeted agent against a compensatory pathway. In BOLERO-2, adding the mTOR inhibitor everolimus to endocrine therapy significantly improved progression-free survival (PFS) in patients with HR+ advanced breast cancer previously treated with nonsteroidal aromatase inhibitor therapy. Notably, PFS benefits were comparable in subgroup analyses of first- and later-line settings. These results contrast with those of the large first-line HORIZON study, wherein adding the mTOR inhibitor temsirolimus to endocrine therapy did not improve PFS. Therefore, it is unclear whether a targeted agent should only be combined with endocrine therapy to restore endocrine sensitivity or whether it may also prevent or delay resistance in hormone-sensitive advanced breast cancer. Numerous additional targeted agents are currently being evaluated in combination with endocrine therapies, including PI3K, cyclin-dependent kinase 4/6, SRC, and histone deacetylase inhibitors. Appropriate patient selection based on prior treatment history will become increasingly important in maximizing the incremental benefit derived from these new agents combined with existing endocrine therapies in HR+ advanced breast cancer. [less ▲]

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See detailUse of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes.
Jerusalem, Guy ULg; RORIVE, Andrée ULg; COLLIGNON, Joëlle ULg

in Breast Cancer (2014), 6

Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents ... [more ▼]

Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents. Recently, everolimus, a mammalian target of rapamycin (mTOR) inhibitor, combined with exemestane, an aromatase inhibitor, has been approved in Europe and the USA for patients suffering from estrogen receptor-positive, HER2-negative advanced breast cancer previously treated by a nonsteroidal aromatase inhibitor, based on the results of BOLERO-2 (Breast cancer trials of OraL EveROlimus). This study showed a statistically significant and clinically meaningful improvement in median progression-free survival. Results concerning the impact on overall survival are expected in the near future. This clinically oriented review focuses on the use of mTOR inhibitors in breast cancer. Results reported with first-generation mTOR inhibitors (ridaforolimus, temsirolimus, everolimus) are discussed. The current and potential role of mTOR inhibitors is reported according to breast cancer subtype (estrogen receptor-positive HER2-negative, triple-negative, and HER2-positive ER-positive/negative disease). Everolimus is currently being evaluated in the adjuvant setting in high-risk estrogen receptor-positive, HER2-negative early breast cancer. Continuing mTOR inhibition or alternatively administering other drugs targeting the phosphatidylinositol-3-kinase/protein kinase B-mTOR pathway after progression on treatments including an mTOR inhibitor is under evaluation. Potential biomarkers to select patients showing a more pronounced benefit are reviewed, but we are not currently using these biomarkers in routine practice. Subgroup analysis of BOLERO 2 has shown that the benefit is consistent in all subgroups and that it is impossible to select patients not benefiting from addition of everolimus to exemestane. Side effects and impact on quality of life are other important issues discussed in this review. Second-generation mTOR inhibitors and dual mTOR-phosphatidylinositol-3-kinase inhibitors are currently being evaluated in clinical trials. [less ▲]

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See detailEuropean inter-institutional impact study of MammaPrint.
Cusumano, P. G.; Generali, D.; Ciruelos, E. et al

in Breast (Edinburgh, Scotland) (2014), 23(4), 423-8

AIM: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort ... [more ▼]

AIM: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort. METHODS: Breast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient. RESULTS: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%. CONCLUSION: The results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients. [less ▲]

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