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See detailExtended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
Colleoni, Marco; Luo, Weixiu; Karlsson, Per et al

in Lancet Oncology (2018), 19(1), 127-138

BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent ... [more ▼]

BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2.5 mg/day orally for 5 years) or intermittent use of letrozole (2.5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2.5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing. FINDINGS: Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85.8% (95% CI 84.2-87.2) in the intermittent letrozole group compared with 87.5% (86.0-88.8) in the continuous letrozole group (hazard ratio 1.08, 95% CI 0.93-1.26; p=0.31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group). INTERPRETATION: In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them. FUNDING: Novartis and the International Breast Cancer Study Group. [less ▲]

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See detailNatural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers.
Latge, Guillaume ULiege; Poulet, Christophe ULiege; Bours, Vincent ULiege et al

in International Journal of Molecular Sciences (2018), 19(1),

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high ... [more ▼]

Natural antisense transcripts are RNA sequences that can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Because strand-specific high-throughput sequencing of the antisense transcriptome has only been available for less than a decade, many natural antisense transcripts were first described as long non-coding RNAs. Although the precise biological roles of natural antisense transcripts are not known yet, an increasing number of studies report their implication in gene expression regulation. Their expression levels are altered in many physiological and pathological conditions, including breast cancers. Among the potential clinical utilities of the natural antisense transcripts, the non-coding|coding transcript pairs are of high interest for treatment. Indeed, these pairs can be targeted by antisense oligonucleotides to specifically tune the expression of the coding-gene. Here, we describe the current knowledge about natural antisense transcripts, their varying molecular mechanisms as gene expression regulators, and their potential as prognostic or predictive biomarkers in breast cancers. [less ▲]

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See detailFirst-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study.
Di Leo, Angelo; Jerusalem, Guy ULiege; Torres, Roberto et al

in Breast (Edinburgh, Scotland) (2018), 38

OBJECTIVES: The double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic ... [more ▼]

OBJECTIVES: The double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease. MATERIALS & METHODS: Progression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings. RESULTS: First-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64-1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64-1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70-1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58-0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population. CONCLUSION: The superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS. [less ▲]

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See detailA randomized phase II study evaluating different maintenance schedules of nab-Paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial.
Gennari, A.; Sun, Z.; Hasler-Strub, U. et al

in Annals of oncology : official journal of the European Society for Medical Oncology (2017)

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short ... [more ▼]

Background: The phase II SNAP trial was designed to evaluate the efficacy of alternative chemotherapy schedules for prolonged administration in HER2-negative metastatic breast cancer (MBC), after a short induction at conventional doses. Methods: Between April 2013 and August 2015, 258 women untreated with chemotherapy for MBC were randomly assigned to receive three different maintenance chemotherapy schedules after three cycles of identical induction chemotherapy: Arm A, nab-Paclitaxel 150 mg/m2 days 1,15 Q28; Arm B, nab-Paclitaxel 100 mg/m2 days 1,8,15 Q28; Arm C, nab-Paclitaxel 75 mg/m2 days 1,8,15,22 Q28. Induction was three cycles nab-Paclitaxel 150/125 mg/m2, days 1,8,15 Q28. The primary objective was to evaluate the efficacy of each maintenance schedule, in terms of progression-free survival (PFS), as compared to the historical reference of 7-month median PFS reported by previous studies with first-line docetaxel. One-sample, one-sided log-rank tests were utilized. Quality-of-life evaluation was performed, global indicator for physical well-being was defined as the primary endpoint; completion rates of quality-of-life forms were >90%. Results: 255 patients were evaluable for the primary endpoint. After 18.2 months median follow-up, 182 PFS events were observed. Median PFS was 7.9 months (90%CI 6.8-8.4) in Arm A, 9.0 months (90%CI 8.1-10.9) in Arm B and 8.5 months (90%CI 6.7-9.5) in Arm C. PFS in Arm B was significantly longer than the historical reference of first-line docetaxel (P=0.03). Grade>/=2 sensory neuropathy was reported in 37.9%, 36.1% and 31.2% of patients in Arm A, Arm B and Arm C, respectively (Grade>/=3 in 9.1%, 5.6% and 6.6% of patients, respectively). Noteworthy, the quality-of-life scores for sensory neuropathy did not worsen with prolonged nab-Paclitaxel administration in any of the maintenance arms. Conclusion: The SNAP trial demonstrated that alternative nab-Paclitaxel maintenance schedules with reduced dosages after a short induction at conventional doses are feasible and active in the first-line treatment of MBC. Registration: ClinicalTrials.gov NCT01746225. [less ▲]

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See detailMultidisciplinary rehabilitation program after breast cancer: benefits on physical function, anthropometry and quality of life.
Leclerc, Anne-France ULiege; Foidart-Dessalle, Marguerite ULiege; Tomasella, Marco ULiege et al

in European Journal of Physical and Rehabilitation Medicine (2017), 53(5), 633-642

BACKGROUND: Different clinical trials show beneficial effects of physical training offered during and / or after breast cancer treatment. However, given the variety of side effects that may be encountered ... [more ▼]

BACKGROUND: Different clinical trials show beneficial effects of physical training offered during and / or after breast cancer treatment. However, given the variety of side effects that may be encountered, physical training could be combined with psychological, relational and social guidance. This kind of multidisciplinary program has been little studied so far. AIM: To determine the benefits of a three-month multidisciplinary rehabilitation program among women after breast cancer treatment. DESIGN: Controlled no-randomized trial. SETTING: University for outcomes, University Hospital Center for interventions. POPULATION: Two hundred and nine outpatients who have been treated for a primary breast carcinoma. METHODS: Patients were divided into a control group (n=106) and an experimental group (n=103) which has benefited from a rehabilitation program of three months including physical training and psycho-educational sessions. The assessments, performed before and after the program, included functional assessments ("Sit and Reach Test", maximal incremental exercise test and "Six-Minute Walk Test"), body composition measurements (body mass index (BMI) and body fat percentage) and a questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30). RESULTS: After three months, flexibility, walking distance and all parameters measured during the maximal incremental exercise, except maximal heart rate, were significantly improved in the experimental group. The body fat percentage was significantly decreased and a significant improvement was observed for perceived health status (quality of life), functional role, emotional state, physical, cognitive and social functions and for most symptoms. In the control group, most of these improvements didn't appear and a significant increase in BMI and body fat percentage was observed. CONCLUSIONS: This trial identifies the benefits of a well detailed multidisciplinary rehabilitation program, including physical re-conditioning and psycho-educational sessions, with important improvements in functional capacity, body composition and the majority of functions and symptoms among women after breast cancer treatment. CLINICAL REHABILITATION IMPACT: Through its results, this study could contribute to the development of hospital quality standards for oncologic rehabilitation. Physiotherapists can efficiently propose this kind of multidisciplinary rehabilitation program. [less ▲]

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See detailCommunication of healthcare professionals: is there ageism?
Schroyen, Sarah ULiege; Adam, Stéphane ULiege; Marquet, Manon ULiege et al

in European Journal of Cancer Care (2017)

Elderspeak is often used when talking to older individuals and is characterized by a slower and/or louder speech, a patronizing tone, etc. A part of the reason of such communication can be found in the ... [more ▼]

Elderspeak is often used when talking to older individuals and is characterized by a slower and/or louder speech, a patronizing tone, etc. A part of the reason of such communication can be found in the actual context of negative view of aging. However, the link between view of aging and elderspeak has never been objectively studied in oncology. Therefore, 40 healthcare professionals (physicians and medical students) record a podcast where they have to explain an endocrine therapy to two fictional patients (40 vs 70 years old). Results show that when participants explained the treatment to the older patient, they used shorter utterances and made more repetitions. They also evoked fewer side effects such as sexual issues. Moreover, reduction of length of utterances and of word-per-minute rate was observed for older patient when participants have a positive view of aging but for both patients when they have a negative view of aging. In conclusion, physicians and medical students used elderspeak when they explained a treatment to older patients. Participants with a more negative view of aging also unconsciously talked slower and made shorter utterances to a 40 year-old patient. [less ▲]

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See detailTranscriptome wide analysis of natural antisense transcripts shows potential role in breast cancer
Wenric, Stéphane ULiege; El Guendi, Sonia; CABERG, Jean-Hubert ULiege et al

Poster (2017, May)

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer ... [more ▼]

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing. To highlight the potential role of NATs in gene regulations occurring in breast cancer, three different gene extraction methods were used: differential expression analysis of NATs between tumor and healthy tissues, differential correlation analysis of paired NAT/PCT between tumor and healthy tissues, and NAT/PCT read count ratio variation between tumor and healthy tissues. Each of these methods yielded lists of NAT/PCT pairs that were demonstrated to be enriched in survival-associated genes on an independent cohort (TCGA). This work allows to highlight NAT lists that display a strong potential to affect the expression of genes involved in the breast cancer pathology. [less ▲]

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See detailThe link between self-perceptions of aging, cancer view and physical and mental health of older people with cancer: A cross-sectional study
Schroyen, Sarah ULiege; Marquet, Manon ULiege; Jerusalem, Guy ULiege et al

in Journal of Geriatric Oncology (2017), 8(1), 64-68

Objectives Older people may suffer from stigmas linked to cancer and aging. Although some studies suggested that a negative view of cancer may increase the level of depression, such an association has ... [more ▼]

Objectives Older people may suffer from stigmas linked to cancer and aging. Although some studies suggested that a negative view of cancer may increase the level of depression, such an association has never been studied in the elderly population. Similarly, even though it is established that a negative self-perception of aging has deleterious consequences on mental and physical health in normal aging, the influence in pathological contexts, such as oncology, has not been studied. The main aim of this study is thus to analyze the effect of these two stigmas on the health of elderly oncology patients. Materials and Methods 101 patients suffering from a cancer (breast, gynecological, lung or hematological) were seen as soon as possible after their diagnosis. Their self-perception of age, cancer view and health (physical and mental) was assessed. Results Multiple regressions showed that patients with a more negative self-perception of aging and/or more negative cancer view reported poorer global health. We also observed that negative self-perception of aging was associated with worse physical and mental health, whereas negative cancer views were only linked to worse mental health. No interaction was observed between these two stigmas, suggesting that their action is independent. Conclusion Older patients with cancer face double stigmatization, due to negative self-perception of aging and cancer, and these stigmas have impacts on global and mental health. Self-perception of aging is also linked to physical health. Longitudinal studies will be necessary to analyze the direction of the association between this double stigmatization and health. [less ▲]

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See detailProtocol update and preliminary results of EACVI/HFA Cardiac Oncology Toxicity (COT) Registry of the European Society of Cardiology.
Lancellotti, Patrizio ULiege; Galderisi, Maurizio; Donal, Erwan et al

in ESC heart failure (2017), 4(3), 312-318

AIMS: European Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of ... [more ▼]

AIMS: European Association of Cardiovascular Imaging/Heart Failure Association Cardiac Oncology Toxicity Registry was launched in October 2014 as a European Society of Cardiology multicentre registry of breast cancer patients referred to imaging laboratories for routine surveillance, suspected, or confirmed anticancer drug-related cardiotoxicity (ADRC). After a pilot phase (1 year recruitment and 1 year follow-up), some changes have been made to the protocol (version 1.0) and electronic case report form. METHODS AND RESULTS: Main changes of the version 2.0 concerned exclusion criteria, registry duration, and clarification of the population characteristics. Breast cancer radiotherapy has been removed as an exclusion criterion, which involves now only history of a pre-chemotherapy left ventricular dysfunction. The period for long-term registry recruitment has been reduced (December 2017), but the target study population was extended to 3000 patients. The characteristics of the population are now better defined: patients seen in an imaging lab, which will include patients undergoing chemotherapy with associated targeted therapy or no targeted therapy, at increased risk of ADRC. In total, 1294 breast cancer patients have been enrolled, and 783 case report forms locked from October 2014 to November 2016. Of these, 481 (61.4%) were seen at first evaluation and 302 (38.6%) while on oncologic treatment with anticancer drugs. Fifty-two patients (17.2%) were not in targeted therapies, 191 (63.3%) were ongoing targeted therapy, and 59 (19.5%) had completed it. Twenty-three (2.9%) patients had a suspected diagnosis and 35 (4.5%) a confirmed diagnosis of ADRC. Arterial hypertension was the most prevalent cardiovascular risk factor (29.2%) followed by diabetes (6.1%). Previous history of heart failure accounted for 0.5%, whereas previous cardiac disease was identified in 6.3% of population. CONCLUSION: The changes of the original protocol of the COT Registry and first update allow a first glance to the panorama of cardiovascular characteristics of breast cancer patients enrolled. [less ▲]

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See detailTranscriptome-wide analysis of natural antisense transcripts shows their potential role in breast cancer.
Wenric, Stéphane ULiege; ElGuendi, Sonia; CABERG, Jean-Hubert ULiege et al

in Scientific Reports (2017), 7(1), 17452

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense ... [more ▼]

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired adjacent non-malignant tissues were analyzed by strand-specific RNA sequencing. To highlight ncNATs potentially playing a role in protein coding gene regulations that occur in breast cancer, three different data analysis methods were used: differential expression analysis of ncNATs between tumor and non-malignant tissues, differential correlation analysis of paired ncNAT/PCT between tumor and non-malignant tissues, and ncNAT/PCT read count ratio variation between tumor and non-malignant tissues. Each of these methods yielded lists of ncNAT/PCT pairs that were enriched in survival-associated genes. This work highlights ncNAT lists that display potential to affect the expression of protein-coding genes involved in breast cancer pathology. [less ▲]

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See detailAvelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.
Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy ULiege et al

in Breast Cancer Research and Treatment (2017)

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the ... [more ▼]

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade >/= 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC. [less ▲]

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See detailPhase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.
Pistilli, B.; Pluard, T.; Urruticoechea, A. et al

in Breast Cancer Research and Treatment (2017)

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as ... [more ▼]

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (>/= 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR >/= 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine. [less ▲]

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See detailAssociation between self-perception of aging, view of cancer and health of older patients in oncology: A one-year longitudinal study
Schroyen, Sarah ULiege; Missotten, Pierre ULiege; JERUSALEM, Guy ULiege et al

in BMC Cancer (2017)

Background: Identifying older people affected by cancer who are more at risk of negative health outcomes is a major issue in health initiatives focusing on medical effectiveness. In this regard ... [more ▼]

Background: Identifying older people affected by cancer who are more at risk of negative health outcomes is a major issue in health initiatives focusing on medical effectiveness. In this regard, psychological risk factors such as patients’ perception of their own aging and cancer could be used as indicators to improve customization of cancer care. We hypothesize that more negative self-perception of aging (SPA) and view of cancer could be linked to worse physical and mental health outcomes in cancer patients. Methods: 101 patients diagnosed with cancer (breast, gynecological, lung or hematological) were followed for one year. They were evaluated on four occasions (baseline, 3, 6 and 12 months after the baseline). Their SPA, view of cancer and health (physical and mental) were assessed at each time of evaluation. Results: Negative SPA and/or view of cancer at baseline are associated with negative evolution of patients’ physical and mental health. Moreover, when the evolution of SPA and cancer view were taken into account, these two stigmas are still linked with the evolution of mental health. In comparison, only a negative evolution of SPA was linked to worse physical health outcomes. Conclusions: Such results indicate that SPA and view of cancer could be used as markers of vulnerability in older people with cancer. [less ▲]

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See detailMT4-MMP and EGFR expression levels are key biomarkers for breast cancer patient response to chemotherapy and erlotinib.
Yip, Cassandre ULiege; Foidart, Pierre ULiege; Somja, Joan ULiege et al

in British Journal of Cancer (2017)

BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a ... [more ▼]

BACKGROUND: Triple-negative breast cancers (TNBC) are heterogeneous cancers with poor prognosis. We aimed to determine the clinical relevance of membrane type-4 matrix metalloproteinase (MT4-MMP), a membrane type matrix metalloproteinase that interacts with epidermal growth factor receptor (EGFR) overexpressed in >50% of TNBC. METHODS: We conducted a retrospective immunohistochemical analysis on human TNBC samples (n=81) and validated our findings in in vitro and in vivo assays. RESULTS: Membrane type-4 matrix metalloproteinase and EGFR are produced in 72.5% of TNBC samples, whereas those proteins are faintly produced by healthy tissues. Unexpectedly, tumour relapse after chemotherapy was reduced in samples highly positive for MT4-MMP. Mechanistically, this is ascribed to a higher sensitivity of MT4-MMP-producing cells to alkylating or intercalating chemotherapeutic agents, as assessed in vitro. In sharp contrast, MT4-MMP expression did not affect tumour cell sensitivity to paclitaxel that interferes with protease trafficking. Importantly, MT4-MMP expression sensitised cancer cells to erlotinib, a tyrosine kinase EGFR inhibitor. In a pre-clinical model, the growth of MT4-MMP overexpressing xenografts, but not of control ones, was reduced by epirubicin or erlotinib. The combination of suboptimal drug doses blocked drastically the growth of MT4-MMP-producing tumours. CONCLUSIONS: We demonstrate that MT4-MMP defines a sub-population of TNBC sensitive to a combination of DNA-targeting chemotherapeutic agents and anti-EGFR drugs.British Journal of Cancer advance online publication 14 February 2017; doi:10.1038/bjc.2017.23 www.bjcancer.com. [less ▲]

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