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Article: Editorial: Heterogeneity in breast cancer: clinical and therapeutic implications.

Carlino, Francesca / Solinas, Cinzia / Orditura, Michele / Bisceglia, Maria Dezia / Pellegrino, Benedetta / Diana, Anna

2024 Volume 14, Page(s) 1321654

Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2024.1321654
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Article: The Innate Immune Microenvironment in Metastatic Breast Cancer.

Tommasi, Chiara / Pellegrino, Benedetta / Diana, Anna / Palafox Sancez, Marta / Orditura, Michele / Scartozzi, Mario / Musolino, Antonino / Solinas, Cinzia

Journal of clinical medicine

2022 Volume 11, Issue 20

Abstract: The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor ... ...

Abstract	The immune system plays a fundamental role in neoplastic disease. In the era of immunotherapy, the adaptive immune response has been in the spotlight whereas the role of innate immunity in cancer development and progression is less known. The tumor microenvironment influences the terminal differentiation of innate immune cells, which can explicate their pro-tumor or anti-tumor effect. Different cells are able to recognize and eliminate no self and tumor cells: macrophages, natural killer cells, monocytes, dendritic cells, and neutrophils are, together with the elements of the complement system, the principal players of innate immunity in cancer development and evolution. Metastatic breast cancer is a heterogeneous disease from the stromal, immune, and biological point of view and requires deepened exploration to understand different patient outcomes. In this review, we summarize the evidence about the role of innate immunity in breast cancer metastatic sites and the potential targets for optimizing the innate response as a novel treatment opportunity.
Language	English
Publishing date	2022-10-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11205986
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Article ; Online: Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial.

Orlando, Laura / Maiello, Evaristo / Orditura, Michele / Diana, Anna / Antoniol, Giuliano / Morritti, Maria Grazia / Aieta, Michele / Ciccarese, Mariangela / Pisconti, Salvatore / Bordonaro, Roberto / Russo, Antonio / Febbraro, Antonio / Schiavone, Paola / Quaranta, Annamaria / Caliolo, Chiara / Loparco, Dario / Cinefra, Margherita / Colucci, Giuseppe / Cinieri, Saverio

Breast (Edinburgh, Scotland)

2024 Volume 75, Page(s) 103725

Abstract: Background: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as ...

Abstract	Background: Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC. Methods: Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity. Results: From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A). Conclusions: First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.
Language	English
Publishing date	2024-04-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1143210-x
ISSN	1532-3080 ; 0960-9776
ISSN (online)	1532-3080
ISSN	0960-9776
DOI	10.1016/j.breast.2024.103725
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Zs.A 3620: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Beyond Platinum, ICIs in Metastatic Cervical Cancer: A Systematic Review.

Maiorano, Brigida Anna / Maiorano, Mauro Francesco Pio / Ciardiello, Davide / Maglione, Annamaria / Orditura, Michele / Lorusso, Domenica / Maiello, Evaristo

Cancers

2022 Volume 14, Issue 23

Abstract: Background: Cervical cancer (CC) constitutes the fourth most common tumor among the female population. Therapeutic approaches to advanced CC are limited, with dismal results in terms of survival, mainly after progression to platinum-based regimens. ... ...

Abstract	Background: Cervical cancer (CC) constitutes the fourth most common tumor among the female population. Therapeutic approaches to advanced CC are limited, with dismal results in terms of survival, mainly after progression to platinum-based regimens. Immune checkpoint inhibitors (ICIs) are remodeling the therapeutic scenario of many solid tumors. The role of ICIs in CC should be addressed. Therefore, we systematically reviewed the latest clinical trials employing ICIs in advanced CC to assess which ICIs have been employed and how ICIs might meet the need for new therapeutic options in terms of efficacy and safety. Methods: The review was conducted following the PRISMA guidelines. The following efficacy outcomes were specifically collected: overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS); for safety: type, number, and grade of adverse events (AEs). Results: A total of 17 studies were analyzed. Anti-PD1 (pembrolizumab, nivolumab, cemiplimab, balstilimab, and tislelizumab), anti-PD-L1 (atezolizumab), and anti-CTLA-4 (ipilimumab, zalifrelimab) agents were employed both as single agents or combinations. Overall ORR ranged from 0% to 65.9%. ORR ranged from 5.9% to 69.6% in PD-L1-positive patients and from 0% to 50% in PD-L1-negative patients. DCR was 30.6-94.1%. mPFS ranged from 2 to 10.4 months. mOS ranged from 8 months to not reached. PD-L1 status did not impact survival. A total of 33.9% to 100% of patients experienced AEs. Conclusion: Immunotherapy represents an appealing strategy for patients with advanced CC, as 2 out of 3 patients seem to respond to ICIs. PD-L1 status might be an indicator of response without impacting survival.
Language	English
Publishing date	2022-12-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14235955
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Article: Post-Irradiation Breast Angiosarcoma: All the Possible Treatments and Electrochemotherapy. Case Report and Literature Review.

Parisi, Simona / Gambardella, Claudio / Iovino, Francesco / Ruggiero, Roberto / Lucido, Francesco Saverio / Nesta, Giusiana / Tolone, Salvatore / Brusciano, Luigi / Fisone, Francesca / Mongardini, Federico Maria / Cozzolino, Giovanni / Della Corte, Carminia Maria / Napolitano, Stefania / Orditura, Michele / Esposito, Rosetta / Docimo, Ludovico

Journal of clinical medicine

2024 Volume 13, Issue 2

Abstract: Breast angiosarcoma is a rare malignancy, accounting for less than 1% of all soft tissue cancers. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite multimodal treatment, angiosarcomas represent an ... ...

Abstract	Breast angiosarcoma is a rare malignancy, accounting for less than 1% of all soft tissue cancers. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite multimodal treatment, angiosarcomas represent an incurable disease for many patients and a significant cause of deterioration in their quality of life. Surgery is a cornerstone in management, but high recurrence rates are reported. Electrochemotherapy (ECT) is a practicable locoregional treatment for patients with advanced angiosarcoma as part of a multimodal therapeutic strategy. The palliative benefits of ECT include optimal patient compliance, good local hemostasis control, and positive local responses. Since only 22 cases are described in the literature, we reported a rare case of RAS treated with ECT after a multidisciplinary approach, including Next Generation Sequencing (NGS). A literature review on the feasibility of ECT in RAS management was also performed.
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13020567
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Article ; Online: Implementation of BRCA mutations testing in formalin-fixed paraffin-embedded (FFPE) samples of different cancer types.

Zannini, Giuseppa / Facchini, Gaetano / De Sio, Marco / De Vita, Ferdinando / Ronchi, Andrea / Orditura, Michele / Vietri, Maria Teresa / Ciardiello, Fortunato / Franco, Renato / Accardo, Marina / Zito Marino, Federica

Pathology, research and practice

2023 Volume 243, Page(s) 154336

Abstract: BRCA1 and BRCA2 are onco-suppressor genes involved in the DNA repair mechanism. The presence of BRCA1/2 mutations confers a higher risk of developing several cancer types. To date, the FDA approved various PARP inhibitors to treat selected BRCA1/2 ... ...

Abstract	BRCA1 and BRCA2 are onco-suppressor genes involved in the DNA repair mechanism. The presence of BRCA1/2 mutations confers a higher risk of developing several cancer types. To date, the FDA approved various PARP inhibitors to treat selected BRCA1/2 mutated oncologic patients. At first, PARP inhibitors were approved for patients with ovarian and breast cancers, and subsequently for metastatic pancreatic adenocarcinoma and metastatic castration-resistant prostate cancer after the treatment with chemotherapy. The current guidelines for BRCA testing are very heterogeneous between the different types of tumors regarding the diagnostic algorithm and the type of sample to analyze, such as the blood for the germline mutations and the tumoral tissue for the somatic mutations. Few data have currently been described regarding the detection of BRCA1/2 somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. In this review, we propose an overview of the BRCA mutations in FFPE samples of several cancers, including breast, ovarian, fallopian tube, primary peritoneal, prostate, and pancreatic cancer. We summarize the types and the frequency of BRCA mutations, the guidelines approved for the test, the molecular assays used for the detection and the PARP inhibitors approved for each tumor type.
MeSH term(s)	Female ; Humans ; Male ; Adenocarcinoma ; BRCA1 Protein/genetics ; Formaldehyde ; Mutation/genetics ; Ovarian Neoplasms/pathology ; Pancreatic Neoplasms/genetics ; Paraffin Embedding ; Poly(ADP-ribose) Polymerase Inhibitors ; Genes, BRCA1 ; Genes, BRCA2 ; Pancreatic Neoplasms
Chemical Substances	BRCA1 Protein ; Formaldehyde (1HG84L3525) ; Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2023-01-23
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154336
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Article ; Online: NTRK gene aberrations in triple-negative breast cancer: detection challenges using IHC, FISH, RT-PCR, and NGS.

Zito Marino, Federica / Buono, Simona / Montella, Marco / Giannatiempo, Rosa / Messina, Francesco / Casaretta, Giovanni / Arpino, Grazia / Vita, Giulia / Fiorentino, Francesco / Insabato, Luigi / Sgambato, Alessandro / Orditura, Michele / Franco, Renato / Accardo, Marina

The journal of pathology. Clinical research

2023 Volume 9, Issue 5, Page(s) 367–377

Abstract: Triple-negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type-agnostic emerging biomarkers approved by the Food and ...

Abstract	Triple-negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type-agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan-TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR), and RNA-based next-generation sequencing (NGS). Of 83 cases, 16 showed pan-TRK positivity although no cases had NTRK-fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT-PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan-TRK IHC. Our data demonstrate that IHC has a high false-positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the NTRK genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations.
MeSH term(s)	Humans ; Receptor, trkA/genetics ; Triple Negative Breast Neoplasms/genetics ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Reverse Transcriptase Polymerase Chain Reaction ; High-Throughput Nucleotide Sequencing
Chemical Substances	Receptor, trkA (EC 2.7.10.1)
Language	English
Publishing date	2023-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2814357-7
ISSN	2056-4538 ; 2056-4538
ISSN (online)	2056-4538
ISSN	2056-4538
DOI	10.1002/cjp2.324
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Article ; Online: Retraction notice to "Antitumor activity of bortezomib in human cancer cells with acquired resistance to anti-epidermal growth factor receptor tyrosine kinase inhibitors" [Lung Cancer 71 (2011) 283-290].

Morgillo, Floriana / D'Aiuto, Elena / Troiani, Teresa / Martinelli, Erika / Cascone, Tina / De Palma, Raffaele / Orditura, Michele / De Vita, Ferdinando / Ciardiello, Fortunato

Lung cancer (Amsterdam, Netherlands)

2023 Volume 181, Page(s) 107226

Language	English
Publishing date	2023-05-09
Publishing country	Ireland
Document type	Journal Article ; Retraction of Publication
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2023.107226
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Cancer Treatment-Induced Bone Loss (CTIBL): State of the Art and Proper Management in Breast Cancer Patients on Endocrine Therapy.

Diana, Anna / Carlino, Francesca / Giunta, Emilio Francesco / Franzese, Elisena / Guerrera, Luigi Pio / Di Lauro, Vincenzo / Ciardiello, Fortunato / Daniele, Bruno / Orditura, Michele

Current treatment options in oncology

2021 Volume 22, Issue 5, Page(s) 45

Abstract: Opinion statement: About 70-80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired ...

Abstract	Opinion statement: About 70-80% of early breast cancer (BC) patients receive adjuvant endocrine therapy (ET) for at least 5 years. ET includes in the majority of cases the use of aromatase inhibitors, as upfront or switch strategy, that lead to impaired bone health. Given the high incidence and also the high prevalence of BC, cancer treatment-induced bone loss (CTIBL) represents the most common long-term adverse event experimented by patients with hormone receptor positive tumours. CTIBL is responsible for osteoporosis occurrence and, as a consequence, fragility fractures that may negatively affect quality of life and survival expectancy. As recommended by main international guidelines, BC women on aromatase inhibitors should be carefully assessed for their fracture risk at baseline and periodically reassessed during adjuvant ET in order to early detect significant worsening in terms of bone health. Antiresorptive agents, together with adequate intake of calcium and vitamin D, should be administered in BC patients during all course of ET, especially in those at high risk of osteoporotic fractures, as calculated by tools available for clinicians. Bisphosphonates, such as zoledronate or pamidronate, and anti-RANKL antibody, denosumab, are the two classes of antiresorptive drugs used in clinical practice with similar efficacy in preventing bone loss induced by aromatase inhibitor therapy. The choice between them, in the absence of direct comparison, should be based on patients' preference and compliance; the different safety profile is mainly related to the route of administration, although both types of drugs are manageable with due care, since most of the adverse events are predictable and preventable. Despite advances in management of CTIBL, several issues such as the optimal time of starting antiresorptive agents and the duration of treatment remain unanswered. Future clinical trials as well as increased awareness of bone health are needed to improve prevention, assessment and treatment of CTIBL in these long-term survivor patients.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Aromatase Inhibitors/adverse effects ; Bone Density/drug effects ; Bone Density Conservation Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Denosumab/therapeutic use ; Diphosphonates/therapeutic use ; Female ; Fractures, Bone/prevention & control ; Humans ; Osteoporosis/chemically induced ; Osteoporosis/diagnosis ; Osteoporosis/therapy
Chemical Substances	Antineoplastic Agents ; Aromatase Inhibitors ; Bone Density Conservation Agents ; Diphosphonates ; Denosumab (4EQZ6YO2HI)
Language	English
Publishing date	2021-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-021-00835-2
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Article ; Online: Does Preoperative Neutrophil to Lymphocyte Ratio Predict Disease-Free Survival Rate in Colorectal Cancer Patients Undergoing Curative Surgery?

Galizia, Gennaro / Lieto, Eva / Orditura, Michele

Annals of surgery

2016 Volume 263, Issue 6, Page(s) e80

Language	English
Publishing date	2016-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000001075
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