13 results on '"Campone, Mario"'
Search Results
2. Impact of HER2 Status on Pathological Response after Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer.
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Domergue, Camille, Martin, Elodie, Lemarié, Camille, Jézéquel, Pascal, Frenel, Jean-Sebastien, Augereau, Paule, Campone, Mario, and Patsouris, Anne
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BREAST cancer prognosis ,ONCOGENES ,CANCER chemotherapy ,MULTIVARIATE analysis ,METASTASIS ,TUMOR classification ,COMBINED modality therapy ,PROGRESSION-free survival ,ODDS ratio ,BREAST tumors ,LONGITUDINAL method - Abstract
Simple Summary: HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer (BC) is an emerging subtype of BC with promising results with antibody drug conjugate (ADC) in the metastatic setting. In the early setting, few data have been reported regarding the predictive and prognostic impact of HER2-low status in triple-negative BC (TNBC). Purpose: Investigates the link between HER2 status and histological response after neoadjuvant chemotherapy in patients with early TNBC. Methods: We retrieved clinical and anatomopathological data retrospectively from 449 patients treated for the first time with standard neoadjuvant chemotherapy for early unilateral BC between 2005 and 2020. The primary endpoint was pathological complete response (pCR, i.e., ypT0 ypN0), according to HER2 status. Secondary endpoints included invasive disease-free survival (I-DFS) and overall survival (OS). Results: 437 patients were included, and 121 (27.7%) patients had HER2-low tumours. The pCR rate was not significantly different between the HER2-low group vs. the HER2-0 group (35.7% versus 41.8%, p = 0.284) in either univariate analysis or multivariate analysis adjusted for TNM classification and grade (odds ratio [OR] = 0.70, confidence interval [CI] 95% 0.45–1.08). With a median follow-up of 72.9 months, no significant survival differences were observed between patients with HER2-low tumours vs. patients with HER2-0 tumours in terms of I-DFS (p = 0.487) and OS (p = 0.329). Conclusions: In our cohort, HER2 status was not significantly associated with pCR in a manner consistent with data published recently on TNBC. However, the prognostic impact of HER2-low expression among TNBC patients warrants further evaluation. [ABSTRACT FROM AUTHOR]
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- 2022
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3. Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial.
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Cabel, Luc, Berger, Frédérique, Cottu, Paul, Loirat, Delphine, Rampanou, Aurore, Brain, Etienne, Cyrille, Stacy, Bourgeois, Hugues, Kiavue, Nicolas, Deluche, Elise, Ladoire, Sylvain, Campone, Mario, Pierga, Jean-Yves, and Bidard, Francois-Clement
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THERAPEUTIC use of antineoplastic agents ,SURVIVAL ,RESEARCH ,LOBULAR carcinoma ,CANCER invasiveness ,RESEARCH methodology ,METASTASIS ,PROGNOSIS ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,BREAST tumors ,LONGITUDINAL method - Abstract
Background: CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).Methods: CirCe01 was a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.Results: Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = [0.6;1.4], p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.Conclusions: Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.Clinical Trial Registration: NCT, NCT01349842, https://clinicaltrials.gov/ct2/show/NCT01349842 , registered 9 May 2011. [ABSTRACT FROM AUTHOR]- Published
- 2021
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4. The EPICURE study: a pilot prospective cohort study of heterogeneous and massive data integration in metastatic breast cancer patients.
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Colombié, Mathilde, Jézéquel, Pascal, Rubeaux, Mathieu, Frenel, Jean-Sébastien, Bigot, Frédéric, Seegers, Valérie, and Campone, Mario
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METASTATIC breast cancer ,DATA integration ,CANCER patients ,LONGITUDINAL method ,COHORT analysis ,HORMONE receptor positive breast cancer ,QUALITY of life ,MENTAL health ,PILOT projects ,SOCIAL networks ,METASTASIS ,PSYCHOLOGICAL tests ,BREAST tumors - Abstract
Background: Breast cancer is the most common cancer in women and the first cancer concerning mortality. Metastatic breast cancer remains a disease with a poor prognosis and about 30% of women diagnosed with an early stage will have a secondary progression. Metastatic breast cancer is an incurable disease despite significant therapeutic advances in both supportive cares and targeted specific therapies. In the management of a metastatic patient, each clinician follows a highly complex and strictly personal decision making process. It is based on a number of objective and subjective parameters which guides therapeutic choice in the most individualized or adapted manner.Methods/design: The main objective is to integrate massive and heterogeneous data concerning the patient's environment, personal and familial history, clinical and biological data, imaging, histological results (with multi-omics data), and microbiota analysis. These characteristics are multiple and in dynamic interaction overtime. With the help of mathematical units with biological competences and scientific collaborations, our project is to improve the comprehension of treatment response, based on health clinical and molecular heterogeneous big data investigation.Discussion: Our project is to prove feasibility of creation of a clinico-biological database prospectively by collecting epidemiological, socio-economic, clinical, biological, pathological, multi-omic data and to identify characteristics related to the overall survival status before treatment and within 15 years after treatment start from a cohort of 300 patients with a metastatic breast cancer treated in the institution.Trial Registration: ClinicalTrials.gov identifier (NCT number): NCT03958136 . Registration 21st of May, 2019; retrospectively registered. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2- breast cancer that had progressed during or after prior endocrine therapy.
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Musolino, Antonino, Campone, Mario, Neven, Patrick, Denduluri, Neelima, Barrios, Carlos H., Cortes, Javier, Blackwell, Kimberly, Soliman, Hatem, Kahan, Zsuzsanna, Bonnefoi, Hervé, Squires, Matthew, Zhang, Yong, Deudon, Stephanie, Shi, Michael M., and André, Fabrice
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FIBROBLAST growth factor receptors ,HORMONE receptors ,HORMONE therapy ,BREAST cancer ,PROGRESSION-free survival ,PROTEIN metabolism ,ANTINEOPLASTIC agents ,BREAST tumors ,CELL receptors ,COMPARATIVE studies ,ESTRADIOL ,HETEROCYCLIC compounds ,RESEARCH methodology ,MEDICAL cooperation ,METASTASIS ,QUINOLONE antibacterial agents ,REOPERATION ,RESEARCH ,RESEARCH funding ,SURVIVAL analysis (Biometry) ,TUMOR classification ,EVALUATION research ,RANDOMIZED controlled trials ,TREATMENT effectiveness ,POSTMENOPAUSE ,DISEASE progression - Abstract
Background: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found in ≤8% of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer cases, is correlated with decreased overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated patients with FGFR pathway-amplified breast cancer.Methods: In this randomized, placebo-controlled phase II trial, we evaluated whether the addition of dovitinib to fulvestrant would improve outcomes in postmenopausal patients with HR+, HER2- advanced breast cancer that had progressed during or after prior ET. Patients were stratified by FGF pathway amplification and presence of visceral disease, and they were randomized 1:1 to receive fulvestrant plus dovitinib or placebo. The primary endpoint was progression-free survival (PFS).Results: From 15 May 2012 to 26 November 2014, 97 patients from 36 centers were enrolled. The frequency of FGF pathway amplification was lower than anticipated, and the study was terminated early owing to slow accrual of patients with FGF pathway amplification. The median PFS (95% CI) was 5.5 (3.8-14.0) months vs 5.5 (3.5-10.7) months in the dovitinib vs placebo arms, respectively (HR, 0.68; did not meet predefined efficacy criteria). For the FGF pathway-amplified subgroup (n = 31), the median PFS (95% CI) was 10.9 (3.5-16.5) months vs 5.5 (3.5-16.4) months in the dovitinib vs placebo arms, respectively (HR, 0.64; met the predefined superiority criteria). Frequently reported adverse events in the dovitinib (diarrhea, nausea, vomiting, asthenia, and headache) and placebo (diarrhea, fatigue, nausea, and asthenia) arms were mostly low grade.Conclusions: The safety profile of dovitinib plus fulvestrant was consistent with the known safety profile of single-agent dovitinib. Dovitinib in combination with fulvestrant showed promising clinical activity in the FGF pathway-amplified subgroup. However, the data reported herein should be interpreted with caution, given that fewer PFS events occurred in the FGF pathway-amplified patients than was expected and that an effect of dovitinib regardless of FGR pathway amplification status cannot be excluded, because the population was smaller than expected.Trial Registration: ClinicalTrials.gov identifier: NCT01528345 . Registered 31 January 2012. [ABSTRACT FROM AUTHOR]- Published
- 2017
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6. Influence of tumour burden on trastuzumab pharmacokinetics in HER2 positive non-metastatic breast cancer.
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Bernadou, Guillemette, Campone, Mario, Merlin, Jean‐Louis, Gouilleux‐Gruart, Valérie, Bachelot, Thomas, Lokiec, François, Rezai, Keyvan, Arnedos, Monica, Diéras, Véronique, Jimenez, Marta, Paintaud, Gilles, and Ternant, David
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TRASTUZUMAB , *EPIDERMAL growth factor , *BREAST cancer , *PHARMACOKINETICS , *METASTASIS - Abstract
Aims Trastuzumab, an antibody binding to epidermal growth factor receptor-2 (HER2), has been approved to treat HER2-positive breast cancer in different settings. This study aimed at evaluating the influence of tumour size on trastuzumab pharmacokinetics (PK) in non-metastatic breast cancer patients treated with short term pre-operative trastuzumab. Methods Trastuzumab PK data were obtained from a multicentre, randomized and comparative study. This antibody was administered pre-operatively to patients with localized HER2-positive breast cancer as a single 4 mg kg−1 loading dose followed by 5 weekly 2 mg kg−1 doses. Trastuzumab concentrations were measured repeatedly using an ELISA technique. Tumour size was evaluated at baseline using breast echography. Trastuzumab pharmacokinetics were studied using a population approach and a two compartment model. The influence of tumour burden on trastuzumab pharmacokinetics was quantified as a covariate. Results A total of 784 trastuzumab concentrations were available from the 79 eligible patients. Estimated parameters (interindiviual standard deviation) were central volume of distribution =2.1 l (23%), peripheral volume of distribution =1.3 l (38%), intercompartment clearance =0.36 l day−1, with an elimination half-life of 11.8 days. Typical clearance was 0.22 l day−1 (19%) and its value was increased with tumour size. In patients with the highest tumour size, trastuzumab clearance was 50% [18%-92%] higher than in patients with the lowest tumour size. Conclusions In non-metastatic breast cancer patients, trastuzumab clearance increases with tumour size. The elimination half-life of trastuzumab was shorter in the present population of patients than in metastatic breast cancer patients previously studied. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Automatic Segmentation of Metastatic Breast Cancer Lesions on 18 F-FDG PET/CT Longitudinal Acquisitions for Treatment Response Assessment.
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Moreau, Noémie, Rousseau, Caroline, Fourcade, Constance, Santini, Gianmarco, Brennan, Aislinn, Ferrer, Ludovic, Lacombe, Marie, Guillerminet, Camille, Colombié, Mathilde, Jézéquel, Pascal, Campone, Mario, Normand, Nicolas, and Rubeaux, Mathieu
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BREAST tumor diagnosis ,DEEP learning ,BIOMARKERS ,METASTASIS ,LEARNING laboratories ,TREATMENT effectiveness ,DIAGNOSTIC imaging ,COMPARATIVE studies ,BIOINFORMATICS ,PATIENT monitoring ,AUTOMATION ,RADIOPHARMACEUTICALS ,DESCRIPTIVE statistics ,DEOXY sugars ,BREAST tumors ,LONGITUDINAL method - Abstract
Simple Summary: In the recent years, several deep learning methods for medical image segmentation have been developed for different purposes such as diagnosis, radiotherapy planning or to correlate images findings with other clinical data. However, few studies focus on longitudinal images and response assessment. To the best of our knowledge, this is the first study to date evaluating the use of automatic segmentation to obtain imaging biomarkers that can be used to assess treatment response in patients with metastatic breast cancer. Moreover, the statistical analysis of the different biomarkers shows that automatic segmentation can be successfully used for their computation, reaching similar performances compared to manual segmentation. Analysis also demonstrated the potential of the different biomarkers including novel/original ones to determine treatment response. Metastatic breast cancer patients receive lifelong medication and are regularly monitored for disease progression. The aim of this work was to (1) propose networks to segment breast cancer metastatic lesions on longitudinal whole-body PET/CT and (2) extract imaging biomarkers from the segmentations and evaluate their potential to determine treatment response. Baseline and follow-up PET/CT images of 60 patients from the EPICURE s e i n m e t a study were used to train two deep-learning models to segment breast cancer metastatic lesions: One for baseline images and one for follow-up images. From the automatic segmentations, four imaging biomarkers were computed and evaluated: SUL p e a k , Total Lesion Glycolysis (TLG), PET Bone Index (PBI) and PET Liver Index (PLI). The first network obtained a mean Dice score of 0.66 on baseline acquisitions. The second network obtained a mean Dice score of 0.58 on follow-up acquisitions. SUL p e a k , with a 32% decrease between baseline and follow-up, was the biomarker best able to assess patients' response (sensitivity 87%, specificity 87%), followed by TLG (43% decrease, sensitivity 73%, specificity 81%) and PBI (8% decrease, sensitivity 69%, specificity 69%). Our networks constitute promising tools for the automatic segmentation of lesions in patients with metastatic breast cancer allowing treatment response assessment with several biomarkers. [ABSTRACT FROM AUTHOR]
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- 2022
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8. A Three-Arm Randomized Phase II Study of Oral Vinorelbine Plus Capecitabine Versus Oral Vinorelbine and Capecitabine in Sequence Versus Docetaxel Plus Capecitabine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines.
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Campone, Mario, Dobrovolskaya, Natalya, Tjulandin, Serjei, Chen, Shin‐Chen, Fourie, Sameul, Mefti, Fawzia, Konstantinova, Maria, Lefresne, Florence, Meheust, Nadege, and Jassem, Jacek
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ANTHRACYCLINES , *ANTIMETABOLITES , *ANTINEOPLASTIC agents , *BREAST tumors , *CONFIDENCE intervals , *METASTASIS , *PATIENT safety , *RESEARCH funding , *STATISTICAL sampling , *STATISTICS , *DOCETAXEL , *DATA analysis , *DATA analysis software , *DESCRIPTIVE statistics , *KAPLAN-Meier estimator - Abstract
Owing to the increased number of patients treated with anthracycline-based adjuvant chemotherapy, there is a need for new effective and tolerable nonanthracycline regimens in metastatic breast cancer. Patients with HER2-negative metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting were randomized to fully oral 3 weekly cycles of the combination of oral vinorelbine with capecitabine (V + C), to the same drugs alternating every three cycles (V↔C), or to the combination of docetaxel and capecitabine (D + C). V was given at 80 mg/m2 (after the first cycle at 60 mg/m2) on days 1 and 8 in the V + C arm and weekly in the V↔C arm, C at 1,000 mg/m2 bid from days 1 to 14, and D on day 1 at 75 mg/m2. The primary end point was disease control rate ( CR + PR + NC ≥ 3 months). A total of 139 patients were randomly assigned to V + C (44 patients), V↔C (47 patients), and D + C (48 patients). After an independent review, the disease control rate in the intent-to-treat population in the V + C, V↔C, and D + C arms [95% CI] was 70.5% [54.8-83.2], 37.0% [23.2-52.5], and 70.8% [55.9-83.1], and the median overall survival 22.2, 19.4, and 24.2 months, respectively. When taken into account the disease control rate, the alternating V↔C regimen seems to be less effective compared with V + C or D + C combinations. Combinations of V + C or D + C showed similar efficacy and a different toxicity profile; V + C induced less neutropenia, infection, hand-foot syndrome, fatigue/asthenia, and alopecia, whereas D + C - less gastrointestinal toxicity. V + C combination constitutes a valuable fully oral alternative option to D + C in patients with metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting, while offering the advantages of an all-oral treatment. [ABSTRACT FROM AUTHOR]
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- 2013
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9. Efficacy of Trastuzumab in Routine Clinical Practice and After Progression for Metastatic Breast Cancer Patients: The Observational Hermine Study.
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EXTRA, JEAN-MARC, ANTOINE, ERIC C., VINCENT-SALOMON, ANNE, DELOZIER, THIERRY, KERBRAT, PIERRE, BETHUNE-VOLTERS, ANNE, GUASTALLA, JEAN-PAUL, SPIELMANN, MARC, MAURIAC, LOUIS, MISSET, JEAN-LOUIS, SERIN, DANIEL, CAMPONE, MARIO, HEBERT, CHRISTOPHE, REMBLIER, CÉLINE, BERGOUGNOUX, LOÏC, CAMPANA, FRANK, and NAMER, MOÏSE
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BREAST tumors ,COMPUTER software ,CONFIDENCE intervals ,LONGITUDINAL method ,MEDICAL cooperation ,METASTASIS ,SCIENTIFIC observation ,ONCOGENES ,REGRESSION analysis ,RESEARCH ,SURVIVAL analysis (Biometry) ,DECISION making in clinical medicine ,TRASTUZUMAB ,DATA analysis ,PREDICTIVE tests ,RETROSPECTIVE studies ,DISEASE progression ,TREATMENT duration ,DRUG administration ,DRUG dosage ,DRUG therapy - Abstract
Background. The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP). Patients and Methods. The study observed 623 patients for ≥2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for ≥30 days following progression or stopped at or before progression. Results. The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months). Conclusion. The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab. [ABSTRACT FROM AUTHOR]
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- 2010
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10. Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer.
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Schettini, Francesco, Giuliano, Mario, Lambertini, Matteo, Bartsch, Rupert, Pinato, David James, Onesti, Concetta Elisa, Harbeck, Nadia, Lüftner, Diana, Rottey, Sylvie, van Dam, Peter A., Zaman, Khalil, Mustacchi, Giorgio, Gligorov, Joseph, Awada, Ahmad, Campone, Mario, Wildiers, Hans, Gennari, Alessandra, Tjan-Heijnen, Vivianne C. G., Cortes, Javier, and Locci, Mariavittoria
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PREVENTION of drug side effects ,THERAPEUTIC use of antineoplastic agents ,COMBINATION drug therapy ,DOXORUBICIN ,METASTASIS ,BREAST tumors ,DRUG toxicity ,HORMONE receptor positive breast cancer ,PHARMACODYNAMICS - Abstract
Simple Summary: Anthracyclines are among the most active chemotherapies in breast cancer (BC). However, they can cause structural and cumulative dose-related cardiac damage; hence, they require careful administration after preliminary functional cardiac assessment and subsequent monitoring, along with a limitation in the cumulative dose delivered. Non-pegylated liposomal doxorubicin (NPLD) has been precisely developed to optimize the doxorubicin toxicity profile, while retaining its therapeutic efficacy, thanks to a reduced diffusion in normal tissues with preserved drug penetrance into cancer sites. This has allowed administration of NPLD beyond a conventional doxorubicin maximum cumulative dose, as well as in patients with cardiac comorbilities or anthracycline pretreatment. At present, NPLD is approved in Europe and Canada in combination with cyclophosphamide as the first line of metastatic HER2-negative BC. However, given the increasing complexity of the therapeutic scenario in this setting, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms. Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m
2 . Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms. [ABSTRACT FROM AUTHOR]- Published
- 2021
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11. Development of a Prognostic Tool to Guide the Decision to Extend Adjuvant Aromatase Inhibitors for up to Ten Years in Postmenopausal Early Breast Cancer Patients.
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Moreau-Bachelard, Camille, Campion, Loïc, Robert, Marie, Kerdraon, Olivier, Renaudeau, Céline, Aumont, Maud, Classe, Jean-Marc, Campone, Mario, and Frénel, Jean-Sébastien
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CANCER patients ,CANCER relapse ,COMPARATIVE studies ,CONFIDENCE intervals ,DECISION support systems ,MEDICAL databases ,INFORMATION storage & retrieval systems ,LONGITUDINAL method ,METASTASIS ,RISK assessment ,TIME ,SOFTWARE architecture ,PROPORTIONAL hazards models ,POSTMENOPAUSE ,AROMATASE inhibitors ,TREATMENT duration ,DESCRIPTIVE statistics ,HORMONE receptor positive breast cancer ,DISEASE risk factors - Abstract
Simple Summary: Postmenopausal women with hormone receptor-positive early breast cancer receive adjuvant aromatase inhibitors (AIs) for five years. However, recurrences still occur at a steady rate over at least twenty years, and extending adjuvant AIs for up to ten years is an option. Our work focuses on a specific population of postmenopausal patients who have already received five years of adjuvant AIs. This population is at high risk of osteoporosis and extending AIs must be carefully decided in line with the potential benefit. In this study, we developed a simple tool to identify women at high risk of relapse despite completing five years of AI treatment. The score it provides is available free of charge upon diagnosis and divides patients into two prognostic groups. Combining that score with comorbidities, bone mineral density, and patient motivation may help the decision-making process to recommend extending adjuvant AIs. Background: The selection of women with hormone receptor-positive (HR+) early breast cancer (EBC) at high risk of relapse after five years (yrs.) of adjuvant aromatase inhibitors (AIs) is crucial, as the benefit of extending AIs is counterbalanced by toxicity. We developed a clinicopathological tool to estimate the residual risk of relapse after five years of adjuvant AIs. Methods: The Institut de Cancérologie de l'Ouest (ICO) database was used to determine a prognostic score of post-five-year AI relapse. Cox regression models estimated our score's prognostic performance. Results: In total, 1105 women were included. Median follow-up was 44 months (IQR = 21–70) post-AI treatment. From the Cox models, we designed a dichotomous prognostic score including the number of macrometastases, age (>70 yrs. vs. ≤70 yrs.), tumor size (≥T2 vs. not), and mitotic activity (≥2 vs. not). Overall, 77.5% of patients were classified as being at low risk and 22.5% at high risk of late recurrence. Low-risk patients had a five- to ten-year local or distant recurrence risk of 7.6% (95% CI, 5.4% to 10.6%) as compared with 26.9% (95% CI, 19.9% to 35.7%) for the high-risk roup. Conclusion: In this study, we developed a simple tool to identify women at high risk of relapse despite completing five years of AIs. [ABSTRACT FROM AUTHOR]
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- 2020
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12. miR-720 is a downstream target of an ADAM8-induced ERK signaling cascade that promotes the migratory and invasive phenotype of triple-negative breast cancer cells.
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Das, Sonia G., Romagnoli, Mathilde, Mineva, Nora D., Barillé-Nion, Sophie, Jézéquel, Pascal, Campone, Mario, and Sonenshein, Gail E.
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CANCER cells ,GENETICS of breast cancer ,PHENOTYPES ,METASTASIS ,METALLOPROTEINASES ,ANIMAL experimentation ,ANIMALS ,BREAST tumors ,CANCER invasiveness ,CELL lines ,CELL physiology ,CELL motility ,CELLULAR signal transduction ,GENES ,GENETIC techniques ,GLYCOPROTEINS ,MEMBRANE proteins ,MICE ,RESEARCH funding ,RNA - Abstract
Background: ADAM8 (a disintegrin and metalloproteinase 8) protein promotes the invasive and metastatic phenotype of triple-negative breast cancer (TNBC) cells. High ADAM8 expression in breast cancer patients is an independent predictor of poor prognosis. Here, we investigated whether ADAM8 regulates specific miRNAs, their roles in aggressive phenotype, and potential use as biomarkers of disease.Methods: Microarray analysis was performed on RNA from MDA-MB-231 cells after transient ADAM8 knockdown using TaqMan miRNA cards. Changes in miRNA levels were confirmed using two ADAM8 siRNAs in TNBC cell lines. Kinase inhibitors, β1-integrin antagonist antibody, and different forms of ADAM8 were employed to elucidate the signaling pathway required for miR-720 expression. miR-720 levels were modulated using a specific antagomiR or a mimic, and effects on aggressive phenotype of TNBC cells were determined using Boyden chamber and 3D-Matrigel outgrowth assays. Plasma was isolated from mice before and after implantation of MDA-MB-231 cells and analyzed for miR-720 levels. Serum samples of TNBC patients were evaluated for their ADAM8 and miR-720 levels.Results: We identified 68 miRNAs differentially regulated upon ADAM8 knockdown, including decreased levels of secreted miR-720. Ectopic overexpression of wild-type ADAM8 or forms that lack metalloproteinase activity similarly induced miR-720 levels. The disintegrin and cysteine-rich domains of ADAM8 were shown to induce miR-720 via activation of a β1-integrin to ERK signaling cascade. Knockdown of miR-720 led to a significant decrease in migratory and invasive abilities of TNBC cells. Conversely, miR-720 overexpression rescued these properties. A profound increase in plasma levels of miR-720 was detected 7 days after TNBC cell inoculation into mouse mammary fat pads when tumors were barely palpable. Concordantly, miR-720 levels were found to be significantly higher in serum samples of TNBC patients with high ADAM8 expression.Conclusions: We have shown for the first time that miR-720 is induced by ADAM8 signaling via ERK and plays an essential role in promoting the aggressive phenotype of TNBCs. miR-720 is elevated in serum of patients with ADAM8-high TNBC and, in a group with other miRNAs downstream of ADAM8, holds promise as a biomarker for early detection of or treatment response of ADAM8-positive TNBCs. [ABSTRACT FROM AUTHOR]- Published
- 2016
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13. Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer
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Francesco Schettini, Sergio Venturini, Mario Giuliano, Matteo Lambertini, David J. Pinato, Concetta Elisa Onesti, Pietro De Placido, Nadia Harbeck, Diana Lüftner, Hannelore Denys, Peter Van Dam, Grazia Arpino, Khalil Zaman, Giorgio Mustacchi, Joseph Gligorov, Ahmad Awada, Mario Campone, Hans Wildiers, Alessandra Gennari, Vivianne Tjan-Heijnen, Rupert Bartsch, Javier Cortes, Ida Paris, Miguel Martín, Sabino De Placido, Lucia Del Mastro, Guy Jerusalem, Giuseppe Curigliano, Aleix Prat, Daniele Generali, Institut Català de la Salut, [Schettini F] Translational Genomics and Targeted Therapies in Solid Tumors, Barcelona, Spain. Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. Department of Medicine, University of Barcelona, Barcelona, Spain. [Venturini S] Department of Economic and Social Sciences, Catholic University of Sacred Heart - Cremona Campus, Cremona, Italy. [Giuliano M] Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. [Lambertini M] Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy. Department of Medical Oncology, U.O.C Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. [Pinato DJ] Division of Cancer, Department of Surgery and Cancer, Imperial College London, SW7 2AZ London, UK. Department of Translational Medicine, Università del Piemonte Orientale 'A. Avogadro', Novara, Italy. [Onesti CE] Clinical and Oncological Research Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Cortes J] International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain. Medica Scientia Innovation Research (MedSIR), Barcelona, Spain. Medica Scientia Innovation Research (MedSIR), Ridgewood, NJ, USA. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain, Vall d'Hebron Barcelona Hospital Campus, Schettini, Francesco, Venturini, Sergio, Giuliano, Mario, Lambertini, Matteo, Pinato, David J, Onesti, Concetta Elisa, De Placido, Pietro, Harbeck, Nadia, Lüftner, Diana, Denys, Hannelore, Van Dam, Peter, Arpino, Grazia, Zaman, Khalil, Mustacchi, Giorgio, Gligorov, Joseph, Awada, Ahmad, Campone, Mario, Wildiers, Han, Gennari, Alessandra, Tjan-Heijnen, Vivianne, Bartsch, Rupert, Cortes, Javier, Paris, Ida, Martín, Miguel, De Placido, Sabino, Del Mastro, Lucia, Jerusalem, Guy, Curigliano, Giuseppe, Prat, Aleix, and Generali, Daniele
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PD-L1 ,Paclitaxel ,Network Meta-Analysis ,BRCA ,Immunoteràpia ,Medicaments antineoplàstics - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Algorismes ,Triple Negative Breast Neoplasms ,Immunotheraphy ,Poly(ADP-ribose) Polymerase Inhibitors ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,B7-H1 Antigen ,Sacituzumab govitecan ,Càncer de mama ,Metastasis ,Breast cancer ,Metàstasi ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Antineoplastic Combined Chemotherapy Protocols ,Medicine and Health Sciences ,Humans ,Radiology, Nuclear Medicine and imaging ,Trastuzumab deruxtecan ,Triple negative breast cancer ,PARP inhibitors ,Bayesian network meta-analysi ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Enzyme inhibitors ,Bayes Theorem ,General Medicine ,neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES] ,Bayesian statistical decision ,Bevacizumab ,PARP inhibitor ,Estadística bayesiana ,Inhibidors enzimàtics ,Oncology ,Settore SECS-S/01 - STATISTICA ,Mama - Càncer - Tractament ,Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES] ,Bayesian network meta-analysis ,Therapeutic algorithm ,Human medicine ,HER2-low ,Immunotherapy ,Pembrolizumab ,Algorithms - Abstract
Immunotherapy; PARP inhibitors; Pembrolizumab Immunoteràpia; Inhibidors de PARP; Pembrolizumab Inmunoterapia; Inhibidores de PARP; Pembrolizumab Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).
- Published
- 2022
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