Publications of Guy JERUSALEM
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See detailTyrosine Kinase Inhibitors in Cancer: Breakthrough and Challenges of Targeted Therapy.
POTTIER, Charles ULiege; Fresnais, Margaux; Gilon, Marie ULiege et al

in Cancers (2020)

Receptor tyrosine kinases (RTKs) are key regulatory signaling proteins governing cancer cell growth and metastasis. During the last two decades, several molecules targeting RTKs were used in oncology as a ... [more ▼]

Receptor tyrosine kinases (RTKs) are key regulatory signaling proteins governing cancer cell growth and metastasis. During the last two decades, several molecules targeting RTKs were used in oncology as a first or second line therapy in different types of cancer. However, their effectiveness is limited by the appearance of resistance or adverse effects. In this review, we summarize the main features of RTKs and their inhibitors (RTKIs), their current use in oncology, and mechanisms of resistance. We also describe the technological advances of artificial intelligence, chemoproteomics, and microfluidics in elaborating powerful strategies that could be used in providing more efficient and selective small molecules inhibitors of RTKs. Finally, we discuss the interest of therapeutic combination of different RTKIs or with other molecules for personalized treatments, and the challenge for effective combination with less toxic and off-target effects. [less ▲]

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See detailBlood eosinophilic relative count is prognostic for breast cancer and associated with the presence of tumor at diagnosis and at time of relapse
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Boulet, Delphine ULiege et al

in Oncoimmunology (2020)

Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes. Methods: Stage I–III ... [more ▼]

Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes. Methods: Stage I–III breast cancer patients were included in the study and classified as REC-high vs low (cutoff 1.5%) or relative lymphocyte count (RLC)-high vs low (cutoff 17.5%). The co-primary endpoints were the breast cancer-specific survival (BCSS) or the time to treatment failure (TTF) in the REC groups. Results: Overall 930 patients were included in the study. We observed a benefit for REC-high vs REC-low in TTF (HR 0.610, 95% CI 0.458–0.812), and in BCSS (HR 0.632, 95% CI 0.433–0.923). Similarly, we observed a better TTF (HR 0.421, 95% CI 0.262–0.677) and BCSS (HR 0.350, 95% CI 0.200–0.614) in RLC-high vs low. A lower relapse rate was observed in the REC-high vs REC-low group (17.1% vs 24.7%, p = 0.005), not confirmed in the multivariate analysis. A lower median REC at baseline and at relapse was observed compared to REC after surgery and during cancer-free follow-up (p < .0001). Conclusions: REC could be a new promising, affordable and accessible predictive and prognostic biomarker in all breast cancer subtypes. [less ▲]

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See detailImpact of self-perception of aging on mortality of older patients in oncology.
Schroyen, Sarah ULiege; Letenneur, Luc; Missotten, Pierre ULiege et al

in Cancer Medicine (2020)

OBJECTIVE: Several studies show that self-perception of aging (SPA) is a significant predictor of mental and physical health. In this study, we analyze the effect of SPA on mortality in the specific ... [more ▼]

OBJECTIVE: Several studies show that self-perception of aging (SPA) is a significant predictor of mental and physical health. In this study, we analyze the effect of SPA on mortality in the specific context of geriatric oncology. METHODS: The sample constituted of 140 individuals aged 65 years and older suffering from a recent nonmetastatic cancer (breast, lung, gynecological, or hematological), followed up to 6 years. We used Cox proportional hazards model to assess the effect of SPA at baseline on mortality. It was adjusted for age, gender, educational and cognitive level, oncological information (the site and kind of cancer), number of comorbidities, and physical and mental health at baseline. RESULTS: Patients were aged 73 years at diagnosis and were more often women (85.7%). Individuals with more negative SPA were 3.62 times more likely to die than those with a more positive SPA, with control of gender, age, education and cognitive level, mental and physical health, the category (breast, lung, gynecological, or hematological), and kind (initial or recurrence) of cancer. CONCLUSIONS: These findings suggest that SPA influence the mortality of older people in the particular context of oncology. Therefore, the need to change our attitudes toward aging and older people implied indirectly by these results is discussed. [less ▲]

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See detailOverall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer.
Slamon, Dennis J.; Neven, Patrick; Chia, Stephen et al

in The New England journal of medicine (2020), 382(6), 514-524

BACKGROUND: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients ... [more ▼]

BACKGROUND: In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival. METHODS: Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment. Survival was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. RESULTS: This analysis was based on 275 deaths: 167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6%) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant. The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group, for a 28% difference in the relative risk of death (hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.00455). The benefit was consistent across most subgroups. In a descriptive update, median progression-free survival among patients receiving first-line treatment was 33.6 months (95% CI, 27.1 to 41.3) in the ribociclib group and 19.2 months (95% CI, 14.9 to 23.6) in the placebo group. No new safety signals were observed. CONCLUSIONS: Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor-positive, HER2-negative advanced breast cancer. (Funded by Novartis; MONALEESA-3 ClinicalTrials.gov number, NCT02422615.). [less ▲]

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See detailEffects of a hypnosis-based intervention on fatigue and sleep difficulties in post-treatment cancer patients
Grégoire, Charlotte ULiege; FAYMONVILLE, Marie-Elisabeth ULiege; VANHAUDENHUYSE, Audrey ULiege et al

in Journal of Psychosocial Oncology Research and Practice (2019, September), 1(1S),

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See detailStudy of the impact of non-pharmacological techniques (self-hypnosis/self-care) on cognitive complaints in cancer patients
Bicego, Aminata Yasmina ULiege; Grégoire, Charlotte ULiege; Cassol, Helena ULiege et al

Conference (2019, May 30)

Cancer diagnosis generates a number of physical, psychological and cognitive impairments such as memory, attentional and informational processing deficits that can undermine patients’ quality of life (QoL ... [more ▼]

Cancer diagnosis generates a number of physical, psychological and cognitive impairments such as memory, attentional and informational processing deficits that can undermine patients’ quality of life (QoL). Self-hypnosis combined to self-care learning have been used in the past years to treat these symptoms, at the moment of diagnosis, during and/or after the cancer treatments. However, the impact of self-hypnosis/self-care upon cognitive difficulties has not been investigated yet.The aim of this study is to better understand the impact of self hypnosis/self-care upon the cognitive functions by means of the Functional Assessment of Cancer Therapy-Cognitive Function1 (FACT-COG). [less ▲]

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See detailState of the art in the treatment of soft tissue sarcomas
GENNIGENS, Christine ULiege; JERUSALEM, Guy ULiege

in Belgian Journal of Medical Oncology (2019), 13(6), 227-233

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See detailHER2+ breast cancer treatment and cardiotoxicity: monitoring and management.
Jerusalem, Guy ULiege; Lancellotti, Patrizio ULiege; Kim, Sung-Bae

in Breast cancer research and treatment (2019)

BACKGROUND: Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2 ... [more ▼]

BACKGROUND: Breast cancer is a leading cause of death for women worldwide, with incidence increasing in lower-income countries. For patients with human epidermal growth factor receptor-2-positive (HER2+) breast cancer, widespread availability of several agents targeting the HER2 receptor has resulted in survival gains over the past decades. However, improved survival has resulted in an increased need for management and mitigation of adverse events associated with anticancer therapy. Cardiac adverse events such as decreased ejection fraction and heart failure have been of particular concern in patients with HER2+ breast cancer. Anti-HER2 agents and chemotherapies (specifically anthracyclines, which are frequently used to treat HER2+ disease) have been associated with cardiotoxicity. As increasing numbers of patients are living longer due to more effective therapy, a better understanding of both monitoring and management of cardiotoxicity is urgently needed. METHODS: A comprehensive review of the literature was conducted via PubMed in January 2018 for phase II and phase III trials of "trastuzumab", "lapatinib", "pertuzumab", "T-DM1", "neratinib", in "breast cancer". Literature was evaluated for content related to cardiac adverse events. FINDINGS: We describe the incidence of and proposed mechanisms for the cardiotoxicity of available HER2-targeted therapies. We summarize current and emerging practices in the management of cardiotoxicity and provide guidance for routine patient care in real-world practice using illustrative patient scenarios. CONCLUSIONS: The future of cardiotoxicity management in patients with HER2+ breast cancer is discussed, with a focus on novel techniques to improve cardiac outcomes, including new imaging modalities, biomarkers, interventional therapies, and ongoing trials. [less ▲]

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See detailTryptophan catabolism increases in breast cancer patients compared to healthy controls without affecting the cancer outcome or response to chemotherapy
ONESTI, Concetta Elisa ULiege; BOEMER, François ULiege; JOSSE, Claire ULiege et al

in Journal of Translational Medicine (2019), 17

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is ... [more ▼]

Background: Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls. Methods: Breast cancer patients and healthy controls were prospectively enrolled in our study. All subjects underwent blood sample withdrawal at diagnosis or on the day of screening mammography for the healthy controls. Plasmatic kynurenine and tryptophan were determined on a TQ5500 tandem mass spectrometer after chromatographic separation. Results: We enrolled 146 healthy controls and 202 women with stages I–III breast cancer of all subtypes. All patients underwent surgery, 126 underwent neoadjuvant chemotherapy with 43 showing a pathological complete response, and 43 underwent adjuvant chemotherapy. We observed significantly higher plasmatic kynurenine, tryptophan and their ratio for the healthy controls compared to patients with breast cancer. We observed a lower plasmatic tryptophan and a higher kynurenine/tryptophan ratio in hormone receptor-negative patients compared to hormone receptor-positive cancers. Lobular cancers showed a lower ratio than any other histologies. Advanced cancers were associated with a lower tryptophan level and higher grades with an increased kynurenine/tryptophan ratio. Pathological complete response was associated with higher kynurenine values. The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratios were not predictive of survival. Conclusions: The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratio could differentiate breast cancer patients from healthy controls. The Kyn/Trp ratio and Trp also showed different values according to hormone receptor status, TNM stage, T grade and histology. These results suggest a rapid metabolism in breast cancer, but no associations with outcome or sensitivity to chemotherapy were observed. [less ▲]

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See detailCDK4/6 inhibition in low burden and extensive metastatic breast cancer: summary of an ESMO Open-Cancer Horizons pro and con discussion.
Awada, Ahmad; Gligorov, Joseph; Jerusalem, Guy ULiege et al

in ESMO Open (2019), 4(6), 000565

In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the ... [more ▼]

In December 2017, ESMO Open-Cancer Horizons convened a round-table discussion on the background and latest data regarding cyclin-dependent kinase (CDK)4/6 inhibitors with endocrine therapy (ET) in the treatment of endocrine-sensitive breast cancer (BC). A review on this discussion was published in summer 2018 (https://esmoopen.bmj.com/content/3/5/e000368).Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Several open questions were identified, which led to a second ESMO Open discussion on CDK4/6 inhibitors, taking place in December 2018 and covered in this article. The panel discussed two important clinical scenarios and the pro and cons of a treatment approach with CDK4/6 inhibitors for each scenario:Endocrine-sensitive BC with non-visceral disease and limited spread of the metastases.Endocrine-sensitive BC with non-life-threatening visceral involvement. Regarding scenario 1, the panel agreed that CDK4/6 inhibitors should be recommended in first-line therapy for most patients if cost and practicality allow. However, the use of single-agent ET with an aromatase inhibitor in the first-line treatment of these patients is still a possibility for a small group of patients with very limited disease, such as one or two bone lesions or limited lymph node involvement. Regarding scenario 2, chemotherapy is the first approach for patients with endocrine-sensitive metastatic BC with life-threatening visceral involvement because of the need for a faster response. The therapeutic approaches for patients with non-life-threatening visceral involvement are still under debate. Nevertheless, CDK4/6 inhibitors are currently the treatment of choice for most patients with a close follow-up of tumour response. A treatment algorithm has been suggested at the round table. [less ▲]

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