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The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This research received no specific grants or funding., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The human body represents the habitat of trillions of symbiotic microorganisms, collectively known as human microbiota, approximately half of which residing in the gut. The development of next-generation sequencing techniques has boosted the profiling of human microbiota in recent years. A growing body of evidence seems to support a strict relationship between the disruption of the mutualistic relationship between the microbiota and the host (i.e., dysbiosis) and the development of several diseases, including breast malignancies. Breast cancer still represents the most frequent cause of cancer-related death in women. Its complex relationship with gut microbiota is the object of a growing body of evidence. In fact, the interaction with the host immune system and a direct impact of gut microbiota on estrogen, lipid and polyphenols metabolism, seem to potentially affect breast tumor development, progression and response to treatments. In this review, in an attempt to help oncologists navigating this rapidly-evolving research field, we provide an essential overview on the taxonomy, main analytical techniques and terminology most commonly adopted. We discuss what is currently known regarding the interaction between gut microbiota and breast cancer and potential efforts to harness this complex interplay for therapeutic purposes, and revise main ongoing studies. We also briefly provide an overview on breast cancer intratumoral microbiota and its potential role beyond gut microbiota., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Schettini reports honoraria from Novartis, Gilead and Daiichy-Sankyo for educational events/materials and travel expenses from Novartis, Gilead and Daiichy-Sankyo. Daniele Generali declares personal fees for educational events by Novartis, Lilly, Pfizer, Daiichy-Sankyo, Roche; research funds from Astrazeneca, Novartis and LILT. The other authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs. To address these concerns, the Italian Association of Multidisciplinary Oncology Groups (AIGOM) orchestrated a Consensus on early Breast Cancer follow-up utilizing the Estimate-Talk-Estimate methodology. Following the identification of 18 Items and 38 statements by a select Board, 46 out of 54 (85.1%) experts comprising a multidisciplinary and multiprofessional panel expressed their degree of consensus (Expert Panel). The Expert Panel underscores the potential for the multidisciplinary team to tailor follow-up intensity based on the individual risk of recurrence. In selected cases, the general practitioner may be recommended as the clinical lead for breast cancer follow-up, both after completion of adjuvant treatment and at early initiation of endocrine therapy in low-risk patients. Throughout follow-up, and alongside oncologic surveillance, the expert panel advises osteometabolic, cardiologic, and gynecologic surveillance for the early detection and management of early and late treatment toxicities. Moreover, preserving quality of life is emphasized, with provisions for psycho-oncologic support and encouragement to adopt protective lifestyle behaviors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Stefania Gori, Fiorenza De Rose, no conflict of interests to declare. Antonella Ferro, honoraria from Novartis, MDS, Daiichi Sankyo, Astra Zeneca, Ely Lilly, Gentili. Alessandra Fabi grants from Astra Zeneca (steering committee); consulting fees from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini; honoraria from Astra Zeneca, Roche, Lilly, Novartis, Gilead, Pfizer, Daiichi Sankyo Exact Sciences; travel grants from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini; advisory board from Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini. Catia Angiolini, Giuseppe Azzarello, Maurizio Cancian, Michela Cinquini, Luca Arecco no conflict of interests to declare. Cynthia Aristei, grants from PRIN 2023, from the Ministry of University and Research. Project title “The microbiome in breast cancer therapy and its potential for pRobIOtics to improve treatment outcome. Acronym: BARRIO”. Daniela Bernardi, Laura Biganzoli, Anna Cariello no conflict of interests to declare. Laura Cortesi, report grants from Astra Zeneca, MSD, Pfizer; consulting fees and honoraria from Astra Zeneca, Gilead, MSD, Roche, Pfizer, Daijchii Sanchio, Novartis; travel grants from Gilead, Pfizer, Daijchi Sanchio; Advisory Board from Astra Zeneca, MSD, Novartis. Elisabetta Cretella no conflict of interests to declare. Carmen Criscitiello, grants from Seagen, Gilead; consulting fees and honoraria from Pfizer, Novartis, Lilly, MSD; Seagen, Daiichi Sankyo, Gilead, AstraZeneca, Roche. Ugo De Giorgi consulting fees from Amgen, Astellas Pharma, Astrazeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck KGaA, MSD, Novartis, Pfizer; travel grants from Pfizer, Ipsen, Astrazeneca. Maria Carmen De Santis, Giuseppe Deledda, Massimo Dessena, Sara Donati, Arianna Dri, Gianluigi Ferretti no conflict of interests to declare. Jennifer Foglietta, honoraria from Novartis; travel grants from Roche, Sophos, Pfizer; Advisory Board from Menarini Stem Line. Davide Franceschini, Pierfrancesco Franco, Alessio Schirone no conflict of interests to declare. Daniele Generali, grants from LILT, University of Trieste, Novartis, Roche; consulting fees from Lilly, Novartis, Pfizer, Roche, Accord, Daiichi Dankyo; honoraria from Lilly, Novartis, Pfizer, Roche, Accord, Daiichi Dankyo, Astrazeneca, Istituto Gentili; travel grants from Roche, Menarini; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Mednote. Lorenzo Gianni, travel grants from Novartis, Lilly, Pfizer; Advisory Board from Astra Zeneca, Novartis, Seagen. Stefano Giordani, Giovanni Grandi, Maria Cristina Leonardi, Stefano Magno, no conflict of interests to declare. Luca Malorni, consulting fees from Menarini, Pfizer, Lilly, Novartis, Roche; travel grants from Roche, Menarini, Celgene, IT Health Fusion; Advisory Board from Novartis. Carlotta Mantoan no conflict of interests to declare. Federica Martorana honoraria from Lilly, Daychii-Sankyo, Pfizer, Astra-Zeneca, Novartis; travel grants from Gilead, Roche, Pfizer, Lilly; advisory board from Amgen. Icro Meattini consulting fees from Pfizer, Astra Zeneca, Daiichi Sankyo, Novartis, Eli Lilly, Seagen, Gilead, Menarini StemLine. Bruno Meduri, Laura Merlini, Federica Miglietta, Alessandra Modena, Fabrizio Nicolis, Isabella Palumbo, no conflict of interests to declare. Pietro Panizza honoraria and travel grants from Bayer AG. Francesca Angela Rovera, Piermario Salvini, Armando Santoro, Mario Taffurelli, no conflict of interests to declare. Angela Toss consulting fees and grants from Lilly, Pfizer, Novartis, MSD, Astrazeneca, Gilead, Seagen, Daiichi Sankyo; travel grants from Gilead, Daiichi Sankyo, Menarini, Astrazeneca. Paolo Tralongo, Monica Turazza, Matteo Valerio, Matteo Verzè no conflict of interests to declare. Patrizia Vici consulting fees from Lilly, Daiichi-Sankyo, Pfizer, MSD, Novartis; honoraria from EISAI, Daiichi-Sankyo, Lilly, Novartis, Pfizer; travel grants from Roche, Pfizer, Daiichi-Sankyo, Novartis, IPSEN; advisory board from Pfizer, Novartis. Claudio Zamagni no conflict of interests to declare. Giuseppe Curigliano advisory board from Roche, Novartis, Lilly, Pfizer, Astra Zeneca, Daichii Sankyo, Ellipsis, Veracyte, Exact Science, Celcuity, Merck, BMS, Gilead, Sanofi, Menarini. Giovanni Pappagallo no conflict of interests to declare. Alberto Zambelli consulting fees Pfizer, Lilly, Novartis, Roche, AstraZeneca, DaiichiSankyo, Seagen, ExactSciences, MSD, Gentili, Gilead; travel grants from Roche, DaiichiSankyo, AstraZeneca, Novartis; advisory board from Roche., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics., Methods: Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed. Relative mRNA expression levels of ERBB2, ESR1, PGR, and MKI67 were measured using the MammaTyper® kit and integrated into a pCR score. Predicting capability of pCR and standard IHC biomarkers could be assessed with ROC curves in 75 and 76 patients, respectively., Results: Overall, 68.0% patients obtained a MammaTyper® high-score and 32.0% a MammaTyper® low-score. Among high-score patients, 62.7% achieved pCR, compared to 16.7% in the low-score group (p = 0.0003). The binary MammaTyper® score showed good prediction of pCR in the overall cohort (area under curve [AUC] = 0.756) and in HR+/HER2-negative cases (AUC = 0.774). In cases with residual disease, the continuous MammaTyper® score correlated moderately with residual tumor size and decrease in tumor size. MammaTyper® showed substantial agreement with IHC for ESR1/ER and ERBB2/HER2, and moderate agreement for PGR/PR and MKI67/Ki67., Conclusion: Overall, MammaTyper® pCR score may serve as a standardized tool for predicting NACT response in HR+/HER2-negative BC, potentially guiding treatment strategies. Additionally, it could provide a more standardized and reproducible assessment of ER, PR, HER2, and Ki67 status., Competing Interests: Declaration of competing interest Francesco Schettini reports honoraria from Novartis, Gilead and Daiichy-Sankyo for educational events/materials and travel expenses from Novartis, Gilead and Daiichy-Sankyo. Daniele Generali declares personal fees for educational events by Novartis, Lilly, Pfizer, Daiichy-Sankyo, Roche; research funds from Astrazeneca, Novartis and LILT. Uğur Şahin is CEO and Mark Laible is an employee of BioNTech SE. Ralph M Wirtz is an employee of STRATIFYER Molecular Pathology GmbH. The other authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Antibody-drug conjugates (ADCs) represent a novel class of molecules composed of a recombinant monoclonal antibody targeted to a specific cell surface antigen, conjugated to a cytotoxic agent through a cleavable or non-cleavable synthetic linker. The rationale behind the development of ADCs is to overcome the limitations of conventional chemotherapy, such as the narrow therapeutic window and the emergence of resistance mechanisms. ADCs had already revolutionized the treatment algorithm of HER2-positive breast cancer. Currently, emergent non-HER2 targeted ADCs are gaining momentum, with special focus on triple-negative disease therapeutic landscape. Sacituzumab govitecan (SG) is an ADC consisting of a humanized monoclonal antibody hRS7 targeting trophoblast cell surface antigen 2 (Trop2), linked to the topoisomerase I inhibitor SN-38 by a hydrolysable linker. It currently stands as the only non-HER2 targeted ADC that already received approval for the treatment of unresectable locally advanced or metastatic triple negative breast cancer (TNBC) in patients who had received two or more prior systemic therapies, with at least one for advanced disease. The purpose of these review is to analyze the available evidence regarding ADCs in TNBC, alongside with providing an overview on the ongoing and future research horizons in this field., Competing Interests: Declaration of competing interest A.D. Has no conflict of interest to declare. G.A. Research and medical writing: AstraZeneca; advisory boards, travel grants, activities as a speaker, consultancy: AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Exact Science, Novartis, Roche, Seagen, Viatris. G.B. Advisory boards, travel grants, consultancy: Seagen, Eli Lilly, Novartis, Pfizer, Roche, AstraZeneca, MSD, Daiichi Sankyio, Eisai, Gilead, Exact Science, Stemline, Agendia. G.C. Advisory boards, activities as a speaker, travel grants, research grants: AstraZeneca, Daichii Sankyo, Lilly, Gilead, MSD, Novartis, Exact Sciences, Menarini, Pfizer, Roche, Seagen. R.D: Advisory boards, activities as a speaker, manuscript writing, travel grants, consultancy: Eisai, GSK, Novartis, AstraZeneca, Eli Lilly, Sanofi, SERB, Roche, Takeda, Pfizer. M.D.L. Advisory boards, activities as a speaker, travel grants, consultancy: Eli Lilly, Novartis, Seagen, Takeda, Roche, Daiichi Sankyo, Tomalab, Gilead, Genetic, Menarini, Sophos, AstraZeneca, Pfizer, Sanofi, Ipsen, Pierre Fabre, GSK. L.D.M. Research grants: Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, AstraZeneca, Gilead, Pierre Fabre; advisory boards, activities as a speaker, travel grants, consultancy: Roche, Novartis, Pfizer, Eli Lilly, Daiichi Sankyo, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, Agendia, Stemline. A.F. Advisory boards: Roche, Novartis, Eli Lilly, Pfizer, MSD, Pierre Fabre, Eisai, Gilead, Seagen, Astra Zeneca, Exact Sciences; consulting fees: Dompé Farmaceutici S.p.A. D.G. Research funding: Menarini, Seagen, Novartis, AstraZeneca; advisory boards, activities as a speaker, consultancy: Seagen, Novartis, Eli Lilly, Roche, Gilead, Pfizer, Eisai, Exact Sciences. A.G. Research grants: Pharmanutra, AAA; advisory boards, activities as a speaker, travel grants, consultancy: Roche, Novartis, Pfizer, Eli Lilly, Daiichi Sankyo, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Stemline. V.G. Advisory board: AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology; activites as a speaker: AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis; expert testimony: Eli Lilly. D.S. Advisory boards: Janssen, EISAI, Roche, Astellas, Daiichi Sankyo, MSD, Merck, Pfizer, Eli Lilly, Novartis, Ipsen, Bayer, Incyte, Gilead. E.S. Advisory boards, activities as a speaker, travel grants: Seagen, Pfizer, Exact Sciences, Daiichi Sankyo, MSD, Gilead, Lilly. C.Z. Research fundings: Roche, Novartis, AstraZeneca, Pfizer, Seattle Genetics, Tesaro, Pierre Fabre, Istituto Gentili, Takeda, TEVA, Medivation, AbbVie, Array BioPharma, Morphotek, Synthon, Daiichi Sankyo, MSD, GSK, Gilead; advisory boards and travel grants: Roche, Eisai, Novartis, AstraZeneca, Pfizer, PharmaMar, Amgen, Tesaro, Quintiles IMS, Pierre Fabre, Istituto Gentili, Eli Lilly, Celgene, Daiichi Sankyo, Exact Sciences, MSD, GSK, Gilead. F.P. Advisory boards, activities as a speaker, travel grants, research grants: AstraZeneca, Daiichi Sankyo, Eisai, Lilly, Gilead, MSD, Novartis, Exact Sciences, Menarini, Pierre Fabre, Pfizer, Roche, Seagen; research funding: AstraZeneca, Eisai, Roche. Funding declaration: This editorial project received financial support thorugh an unconditional grant from Gilead. The funding source had no involvement in the project's design, data collection, analysis, data interpretation, article writing, or the decision to submit it for publication., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Intracranial dermoid cyst (DC) is a rare benign, slow-growing lesion, most commonly arising along the midline. They can occur in the supratentorial compartment, very rarely involve the sellar region and only exceptionally are intrasellar. The aim of our study is to address the challenges in the diagnosis and management of sellar DCs., Methods: We performed a systematic review of sellar DCs, in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and described an intrasellar DC in a 32-year-old female who presented with bilateral blurring vision., Results: The review identified 4 intrasellar, 29 suprasellar, and 28 parasellar cases. Intrasellar DCs more likely present with progressive visual impairment and pituitary hormone dysfunctions during the fifth decade of life. Suprasellar and parasellar DCs are typically diagnosed during the third decade of life because of diplopia, ptosis, trigeminal hypoaesthesia/para-esthesia or cyst's rupture. Sellar DCs are typically hypodense on computed tomography scans and contain calcifications. Magnetic resonance imaging features include T1 hyperintensity, T2 heterogeneous intensity, no restriction on diffusion-weighted images, and no contrast enhancement. Surgery is the treatment of choice. Gross total resection is achieved in 60% of intrasellar and 61.9% of suprasellar and parasellar DCs. Early postoperative complications are reported in 40.0%, 16.7%, and 23.8% of intrasellar, suprasellar, and parasellar DCs, respectively., Conclusions: Intrasellar DCs are rare lesions typically diagnosed later than suprasellar and parasellar DCs due to their different clinical presentations. However, they should be considered in the differential diagnosis of cystic lesions of the sella, including epidermoid cysts, craniopharyngiomas, Rathke's cleft cysts, and teratomas., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Clinical trials confirmed the beneficial effects of adding pertuzumab (P) to the combination of trastuzumab-chemotherapy (TC) in the (neo)adjuvant setting of high-risk HER2-positive early breast cancer (HER2+BC). We evaluated the clinical, economic and societal impact of adding pertuzumab to neoadjuvant TC combination (TPC) in Italy., Methods: A cost-consequence analysis comparing TPC vs. TC was performed developing a cohort-based multi-state Markov model to estimate the clinical, societal and economic impact of the neoadjuvant therapy of TPC versus TC in HER2+BC at high-risk of recurrence. The model works on a cycle length of 1 month and 5-years-time horizon. Literature review-based data were used to populate the model. The following clinical and economic outcomes were estimated: cumulative incidence of loco-regional/distant recurrences, life of years and QALY and both direct and indirect costs (€). Finally, sensitivity analyses were performed., Results: TPC was associated with a 75,630 € saved of direct costs. Specifically, it was associated with an initial increase of treatment costs (+4.8%) followed by reduction of recurrence management cost (-20.4%). TPC was also associated with an indirect cost reduction of 1.40%, as well as decreased incidence of distant recurrence (-20.14%), days of work lost (-1.53%) and days lived with disability (-0.50%). Furthermore, TPC reported 10,47 QALY gained (+2.77%) compared to TC. The probability to achieve the pathological complete response (pCR) was the parameter that mostly affected the results in the sensitivity analysis., Conclusion: Our findings suggested that TPC combination could be a cost-saving option in patients with HER2+BC at high-risk of recurrence., Competing Interests: Declaration of competing interest AZ, MC, NLV, EM, ICA, SDC, AM, DG have no conflicts of interest to disclose. DG has received Honoraria from Novartis, Lilly, Roche, Pfizer, Istituto Gentili. Research funding from profit organizations as Astrazeneca, Novartis and Myriad. PAC has received a research grant from Baxalta now part of Shire, and speaking honoraria from Pfizer, Roche and Novartis. LGM has received grants and personal fees from Bayer AG, Boehringer Ingelheim, Pfizer and Daiichi-Sankyo. MN is employes of Novartis Pharma AG., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: A standardized definition and classification of primary posterior petrous meningiomas (PPMs) is lacking, with consequent challenges in comparing different case series. This study aimed to provide an anatomical description and classification of PPMs analyzing a homogeneous series of patients operated via the retrosigmoid approach., Methods: PPMs originate laterally to the petro-occipital fissure within the venous ring composed of the superior petrosal, sigmoid, inferior petrosal, and cavernous sinuses. We proposed a classification based on tumor site of origin, direction of growth relative to the internal acoustic meatus, and cranial nerves' displacement. Four types of PPMs were defined: retromeatal (type A), meatal (type B), premeatal (type C), and broad-based (type D). We performed a retrospective analysis of 130 consecutive patients with PPMs who underwent surgery as first-line treatment., Results: The PPM classification predicted clinical presentation, postoperative morbidity, and resection rates. Headache, hydrocephalus, and cerebellar deficits were more common in type A (59.0%, 37.7%, 49.2%) and type D (66.7%, 66.7%, 33.3%). Hypoacusia/anacusia was more common in type B (87.5%), while trigeminal hypoesthesia/anesthesia was more common in type C (85.0%). After surgery, patients with type A and D PPMs were at higher risk to develop cerebellar deficits (11.5%-22.2%), whereas patients with type B and C PPMs presented with hypoacusia/anacusia (12.5%) and trigeminal deficits (10.0%), respectively. The near-total resection rate was higher in type A (91.8%), followed by types B (82.5%), C (80.0%), and D (77.8%) PPMs., Conclusions: The PPM surgical classification has an operative and prognostic relevance. In expert hands, the retrosigmoid approach represents a safe and effective approach to remove PPMs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Triple-negative (TN) metastatic breast cancer (mBC) represents the most challenging scenario withing mBC framework, and it has been only slightly affected by the tremendous advancements in terms of drug availability and survival prolongation we have witnessed in the last years for advanced disease. However, although chemotherapy still represents the mainstay of TN mBC management, in the past years, several novel effective agents have been developed and made available in the clinical practice setting. Within this framework, a panel composed of a scientific board of 17 internationally recognized breast oncologists and 42 oncologists working within local spoke centers, addressed 26 high-priority statements, including grey areas, regarding the management of TN mBC. A structured methodology based on a modified Delphi approach to administer the survey and the Nominal Group Technique to capture perceptions and preferences on the management of TN mBC within the Italian Oncology community were adopted. The Panel produced a set of prioritized considerations/consensus statements reflecting the Panel position on diagnostic and staging approach, first-line and second-line treatments of PD-L1-positive/germline BRCA (gBRCA) wild-type, PD-L1-positive/gBRCA mutated, PD-L1-negative/gBRCA wild-type and PD-L1-negative/gBRCA mutated TN mBC. The Panel critically and comprehensively discussed the most relevant and/or unexpected results and put forward possible interpretations for statements not reaching the consensus threshold., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FM reports personal fees from Gilead, Novartis, Roche; AF reports personal fees and non-financial supports for scientific consult, advisory board, lectures from Roche, Novartis, Lilly, Pfizer, MSD, Dompè, Pierre Fabre, Eisai, Sophos, Epionpharma, Gilead, Seagen, Astra Zeneca, Exact Science; DG reports Honoraria from Novartis, Roche, Pfizer and Eli Lilly, Research Funding from Novartis and Astra-Zeneca; MVD reports personal fees from Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen; GB reports honoraria for Consultancy: Roche, AstraZeneca, MSD, Daiichi Sankyo, Gilead, Sanofi, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Chugai, EISAI, Gilead, Seagen, Neopharm Israel, Support for attending meetings and/or travel: Roche, Pfizer, MSD, Chugai, Novartis, Advisory Board: Roche, Pfizer, AstraZeneca, Lilly, Novartis, Amgen, MSD, Chugai, Daiichi Sankyo, EISAI, Gilead, Seagen, Exact Science; GC reports Honoraria for speaker's engagement: Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, BMS, MSD; Honoraria for providing consultancy: Roche, Seattle Genetics, NanoString; Honoraria for participating in Advisory Board: Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, Mylan; Honoraria for writing engagement: Novartis, BMS; Honoraria for participation in Ellipsis Scientific Affairs Group; Institutional research funding for conducting phase I and II clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dome, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune; FP reports Honoraria for advisory boards, activities as a speaker, travel grants, research grants Amgen - Astrazeneca - Daichii Sankyo - Celgene - Eisai - Eli Lilly- Gilead - Ipsen - MSD - Novartis - Pierre Fabre - Pfizer - Roche - Seagen - Takeda – Viatris Research funding Astrazeneca – Eisai – Roche; AZ reports personal fees and non-financial support from Novartis, AstraZeneca, Lilly, Pfizer, Daiichi Sankyo, MSD, Roche, Seagen, Exact Sciences, Gilaed, Istituto Gentili; VG reports personal fees for advisory board membership from Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Olema Oncology and Sanofi, personal fees as an invited speaker from Amgen, Eli Lilly, GSK , Astra Zeneca, Novartis, personal fees for expert testimony from Eli Lilly, institutional funding as a local PI from AstraZeneca, BMS, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, MSD, Nerviano, Novartis, Roche and Synton Biopharmaceutical., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Giuliano, Arpino and De Placido S have declared honoraria from Roche, Pfizer, Astra-Zeneca, Novartis, Celgene, Eli Lilly, Amgen, and Eisai, outside of the submitted work. Dr Lambertini has declared personal fees (advisory role and/or speaker honoraria) from Roche, Takeda, Sandoz, Eli Lilly, Pfizer, AstraZeneca, Novartis Exact Sciences and Ipsen, outside of the submitted work. Dr Bartsch has declared honoraria from AstraZeneca, Daiichy Sankyo, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Roche, consulting or advisory role for AstraZeneca, Daiichi, Eisai, Eli Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Puma Biotechnology, Roche, research funding from Daiichi-Sankyo, travel, accommodations, expenses from Roche, Pfizer, outside of the submitted work. Dr Pinato has received lecture fees from ViiV Healthcare and Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, and Astra Zeneca; research funding (to institution) from MSD and BMS, outside of the submitted work. Dr Harbeck has declared stocks and other ownership interests in the West German Study Group, honoraria from Roche, Novartis, Daiichi-Sankyo, Amgen, Pfizer, Exact Sciences, AstraZeneca, Pierre Fabre, SeaGen; consulting or advisory role for Roche/Genentech, Novartis, Pfizer, Eli Lilly, Sandoz, Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme, Sandoz, SeaGen, Pierre Fabre and research funding to institution from Roche/Genentech, Eli Lilly, Merck Sharp & Dohme, outside of the submitted work. Dr Lüftner has received honoraria from Amgen, AstraZeneca, Celgene, Eisai, Genomic Health, Eli Lilly, Loreal, MSD, Novartis, Pierre Fabre, Pfizer, Tesaro, Teva, outside of the submitted work. Dr Denys has reported consulting fees (advisory role) paid to her institution by Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, Tesaro; grants from Research Funding institutional Roche; and other fees (travel, accommodations, expenses) by Pfizer, Roche, PharmaMar, Teva, AstraZeneca, outside of the submitted work. Dr Zaman has reported travel, accommodation and expenses from Roche, Pierre Fabri and MSD Oncology, research funding from Roche/Genentech consulting/advisory role for Roche, Eli Lilly, MSD Oncology, Mylan, Novartis, Daiichy and Pierre Fabre, and other relationships with Pierre Fabre, all outside the submitted work. Dr Gligorov has declared speakers’ bureau honoraria from Roche-Genentech, Novartis, Eisai, Genomic Health, Ipsen, Pfizer, Mylan, Eli Lilly, Sandoz, and Pierre-Fabre; consultant/advisory board member for Roche-Genentech, Novartis, Onxeo, Daichii Sanyo, MSD, Eisai, Genomic Health, Ipsen, Macrogenics, Pfizer, Mylan, Eli Lilly, Immunomedics, Pierre-Fabre; grant support from Roche-Genetech, Eisai, Genomic Health, Pfizer, Mylan; travel, accommodation paid by Roche-Genentech, Novartis, Eisai, Genomic Health, Pfizer, Eli Lilly, Pierre-Fabre; personal fees and non-financial support from Daichii Sanyo, MSD, outside of the submitted work. Dr Awada reports advisory roles, travel grants, and speaker fees from Roche, Eli Lilly, Amgen, ESAI, BMS, Pfizer, Novartis, MSD, Ipsen, and Leopharma. Dr Campone has declared honoraria from Novartis, Eli Lilly, GT1, Consulting or Advisory Role from Novartis, Servier, Menarini, Sanofi, Eli Lilly, Pfizer, AstraZeneca/MedImmune, Abbvie, Pierre Fabre, Accord Healthcare, Sandoz-Novartis, Seattle Genetics, Daiichi Sankyo Europe GmbH, Speakers' Bureau from Novartis, Amgen, Research Funding from Novartis, Travel, Accommodations, Expenses from Novartis, AstraZeneca, Pfizer, Other Relationship from Roche, outside of the submitted work. Dr Wildiers has declared Consulting or Advisory Role from Roche, Eli Lilly, Pfizer, Sirtex Medical, Orion Corporation, Puma Biotechnology, AstraZeneca, Biocartis, Novartis, Daiichi Sankyo, Research Funding from Roche, Novartis, Travel, Accommodations, Expenses from Pfizer, Roche, outside of the submitted work. Dr Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds from EISAI, Eli Lilly, and Roche, outside of the submitted work. Dr Tjan-Heijnen has declared Honoraria and Travel expenses from Novartis, Roche, Eli Lilly, Pfizer and Honoraria from Daichii Sankyo, as well as Research Funding from Roche, Eisai, Pfizer, Novartis, Eli Lilly, AstraZeneca and Daichii Sankyo, outside of the submitted work. Dr Cortes has declared Stock and Other Ownership Interests from MedSIR, Honoraria from Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Eli Lilly, Merck Sharp & Dohme, Daiichi Sankyo, Consulting or Advisory Role from Celgene, Cellestia Biotech, AstraZeneca, Biothera, Merus, Roche, Seattle Genetics, Daiichi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Eli Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology, Bioasis, Boehringer Ingelheim, Research Funding from ARIAD, Astrazeneca, Baxalta, Bayer, Eisai, Guardant Health, Merck Sharp & Dohme, Pfizer, Puma Biotechnology, Queen Mary University of London, Roche, Piqur, Travel, Accommodations, Expenses from Roche, Pfizer, Eisai, Novartis, Daiichi Sankyo, outside of the submitted work. Dr Del Mastro acted as a consultant for Roche, Novartis, MSD, Pfizer, Ipsen, AstraZeneca, Genomic Health, Eli Lilly, Seattle Genetics, Eisai, Pierre Fabre, and Daiichi Sankyo, received speaker honoraria from Roche, Novartis, Eli Lilly and MSD, and travel grants from Roche, Pfizer and Celgene, outside the submitted work. Dr Martin has declared Honoraria from Roche/Genentech, Eli Lilly, Pfizer, Novartis, Pierre Fabre, Consulting or Advisory Role from Roche/Genentech, Novartis, Pfizer, Eli Lilly, AstraZeneca, Taiho Pharmaceutical, PharmaMar, Speakers' Bureau from Eli Lilly/ImClone, Roche/Genentech, Pierre Fabre, Research Funding from Novartis, Roche, Puma Biotechnology, outside of the submitted work. Dr Curigliano has reported personal fees from Roche, Pfizer, Novartis, Eli Lilly, Foundation Medicine, BMS, Samsung, Astra Zeneca, Daichii Sankyo Boeringer, GSK, Seagen, non-financial support from Roche, Pfizer, grants from Merck, other from Ellipsis, outside the submitted work. Dr Jerusalem has reported grants, personal fees and non-financial support from Novartis, Roche and Pfizer, personal fees and non-financial support from Eli Lilly, Amgen, BMS and Astra-Zeneca, personal fees from Daiichi Sankyo and Abbvie, non-financial support from Medimmune and MerckKGaA, outside the submitted work. Dr Prat reports grants and personal fees from Pfizer, grants and personal fees from Eli Lilly, personal fees from Nanostring tecnologies, grants and personal fees from Amgen, grants from Roche, personal fees from Oncolytics Biotech, Daiichi Sankyo, PUMA, BMS, consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb and patent PCT/EP2016/080056, outside of the submitted work. Dr Prat is also an equity stockholder, founder and consultant of Reveal Genomics and has a patent HER2DX and WO 2018/103834 licensed to Reveal Genomics, all outside of the submitted work. Dr Generali has declared Honoraria from Novartis and Eli Lilly, Research Funding from Novartis and Astra-Zeneca, outside of the submitted work. All other authors declared nothing to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting., Patients and Methods: We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian 'real-world' setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant., Results: Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P = 0.095)., Conclusions: Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials., Competing Interests: Disclosure MG, GA and SDP have declared honoraria from Roche, Pfizer, Astra-Zeneca, Novartis, Celgene, Eli Lilly, Amgen and Eisai outside the submitted work. ML acted as consultant for Roche, AstraZenenca, Novartis, and received speaker honoraria from Roche, Takeda, Novartis, Lilly, Pfizer, Sandoz outside the submitted work. LDM has declared honoraria from Roche, Pfizer, Ipsen, Eli Lilly, Eisai, Novartis, Takeda and Merck Sharp & Dohme (MSD), consulting/advisory role for Roche and Eli Lilly, travels, accommodations and expenses from Roche, Pfizer and Celgene outside the submitted work. MDL has declared consulting fees from Pfizer, Novartis, Eli Lilly, Roche, Eisai, Celgene. FP has declared honoraria for advisory boards, activities as a speaker, travel grants, research grants from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Ipsen, MSD, Novartis, Pierre-Fabre, Pfizer, Roche and Takeda, and research funding from AstraZeneca, Eisai, Roche and Italian Ministry of Health outside the submitted work. PFC reports grants from Merck KGaA, Roche and Bristol-Myers Squibb; grants and personal fees from Novartis and EliLilly; personal fees from AstraZeneca, outside the submitted work. VG reports personal fees from Novartis, Roche, EliLilly, MSD, outside the submitted work. DG has declared consulting fees from Novartis, Lilly and Pfizer, research funding from LILT, Novartis, AstraZeneca and University of Trieste outside the submitted work. GB received honoraria for speaker activities and travel grants from GlaxoSmithKline, Novartis, Pfizer, Roche, Genetic Spa, outside the submitted work. FM declared advisory role for Roche, Novartis, AstraZeneca, Pfizer, Eli Lilly, Pierre Fabre, Daiichi Sankyo, travel grants from Roche and financial support from the Fondazione Piemontese per la Ricerca sul Cancro (FPRC) Onlus 5 x mille funding from the Italian Ministry of Health 2017 outside the submitted work. AF has declared honoraria for advisory board from Roche and Novartis, activity as speaker for Pfizer and Lilly, travel grant from Roche, Novartis, Pfizer, Lilly and AstraZeneca outside the submitted work. The other authors have nothing to declare. Data sharing The anonymized database is available from the corresponding author upon reasonable request. The R codes used are available from the corresponding author upon reasonable request., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Canakinumab is an IL-1β antibody that neutralises the activity of IL-1β. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia., Design: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2)., Results: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO 2 :FiO 2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9-96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6-89.1) for Cohort 2., Conclusions: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with cancer have high risk for severe complications and poor outcome to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease [coronavirus disease 2019 (COVID-19)]. Almost all subjects with COVID-19 develop anti-SARS-CoV-2 immunoglobulin G (IgG) within 3 weeks after infection. No data are available on the seroconversion rates of cancer patients and COVID-19., Patients and Methods: We conducted a multicenter, observational, prospective study that enrolled (i) patients and oncology health professionals with SARS-CoV-2 infection confirmed by real-time RT-PCR assays on nasal/pharyngeal swab specimens; (ii) patients and oncology health professionals with clinical or radiological suspicious of infection by SARS-CoV-2; and (iii) patients with cancer who are considered at high risk for infection and eligible for active therapy and/or major surgery. All enrolled subjects were tested with the 2019-nCoV IgG/IgM Rapid Test Cassette, which is a qualitative membrane-based immunoassay for the detection of IgG and IgM antibodies to SARS-CoV-2. The aim of the study was to evaluate anti-SARS-CoV-2 seroconversion rate in patients with cancer and oncology health care professionals with confirmed or clinically suspected COVID-19., Results: From 30 March 2020 to 11 May 2020, 166 subjects were enrolled in the study. Among them, cancer patients and health workers were 61 (36.7%) and 105 (63.3%), respectively. Overall, 86 subjects (51.8%) had confirmed SARS-CoV-2 diagnosis by RT-PCR testing on nasopharyngeal swab specimen, and 60 (36.2%) had a clinical suspicious of COVID-19. Median time from symptom onset (for cases not confirmed by RT-PCR) or RT-PCR confirmation to serum antibody test was 17 days (interquartile range 26). In the population with confirmed RT-PCR, 83.8% of cases were IgG positive. No difference in IgG positivity was observed between cancer patients and health workers (87.9% versus 80.5%; P = 0.39)., Conclusions: Our data indicate that SARS-CoV-2-specific IgG antibody detection do not differ between cancer patients and healthy subjects., Competing Interests: Disclosure DG reports personal fees for consulting, advisory role and speakers' bureau from Novartis, Pfizer, Lilly; fees for travel and accommodations from Novartis, Pfizer, Lilly. GC reports personal fees for consulting, advisory role, and speakers' bureau from Roche/Genentech, Novartis, Pfizer, Lilly, Foundation Medicine, Samsung, and Daichii-Sankyo; honoraria from Ellipses Pharma; fees for travel and accommodations from Roche/Genentech, and Pfizer. The other authors have declared no conflicts of interest. Data sharing All data generated or analyzed during this study are included in the published article. Additional supporting data are available from the corresponding author on reasonable request. All requests for raw and analyzed data and materials will be reviewed by the corresponding author to verify whether the request is subject to any intellectual property or confidentiality obligations., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: COVID-19 appeared in late 2019, causing a pandemic spread. This led to a reorganisation of oncology care in order to reduce the risk of spreading infection between patients and healthcare staff. Here we analysed measures taken in major oncological units in Europe and the USA., Methods: A 46-item survey was sent by email to representatives of 30 oncological centres in 12 of the most affected countries. The survey inquired about preventive measures established to reduce virus spread, patient education and processes employed for risk reduction in each oncological unit., Results: Investigators from 21 centres in 10 countries answered the survey between 10 April and 6 May 2020. A triage for patients with cancer before hospital or clinic visits was conducted by 90.5% of centres before consultations, 95.2% before day care admissions and in 100% of the cases before overnight hospitalisation by means of phone calls, interactive online platforms, swab test and/or chest CT scan. Permission for caregivers to attend clinic visits was limited in many centres, with some exceptions (ie, for non-autonomous patients, in the case of a new diagnosis, when bad news was expected and for terminally ill patients). With a variable delay period, the use of personal protective equipment was unanimously mandatory, and in many centres, only targeted clinical and instrumental examinations were performed. Telemedicine was implemented in 76.2% of the centres. Separated pathways for COVID-19-positive and COVID-19-negative patients were organised, with separate inpatient units and day care areas. Self-isolation was required for COVID-19-positive or symptomatic staff, while return to work policies required a negative swab test in 76.2% of the centres., Conclusion: Many pragmatic measures have been quickly implemented to deal with the health emergency linked to COVID-19, although the relative efficacy of each intervention should be further analysed in large observational studies., Competing Interests: Competing interests: HSR reported fundings to the Institution from Eisai, Genentech, Lilly, Macrogenics, Merk, Novartis, OBI Pharma, Odonate Therapeutics, Immunomedics, Daiichi-Sankyo and Pfizer; travel fees from Pfizer, Novartis, MacroGenics, Mylan, Daiichi-Sankyo and AstraZeneca; consulting roles for Samsung and Celtrion. MM reported personal fees from Roche, Novartis, Puma, AstraZeneca, Amgen, Taiho Oncology, Daiichi-Sankyo, PharmaMar, Eli-Lilly and Pfizer; grants from Roche, Novartis and Puma. MC reported a grant from Pfizer; personal fees from CytoDyn, Pfizer, Eli-Lilly, Novartis, Foundation Medicine, G1 Therapeutics, Sermionex and Genentech. JC reported funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardanth health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C and Queen Mary University of London; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Eli-Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; travel fees from Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo; consulting/advisor role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi-Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology and Boehringer Ingelheim; stock, patents and intellectual property of MedSIR. SAH reported grants from Ambrx, Amgen, Arvinas, Bayer, Daiichi-Sankyo, Genentech/Roche, GSK, Immunomedics, Eli-Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, Puma, Radius, Sanofi, Seattle Genetics and Dignitana; travel fees from Lilly and Novartis; stock options from NK Max; editorial support from Roche/Genetech, Eli-Lilly and Pfizer. MT declares travel, accomodations, expenses by Roche, Bristol-Myers Squibb, Astra Zeneca, Takeda; activity as medical writer supported by Novartis and Amgen, outside the present work. MC reported funding to the institution from Sanofi, Pierre-Fabre, AstraZeneca, Servier, Novartis, Abbvie, Accord and Pfizer; personal fees from GT1, Sanofi, Pierre-Fabre, AstraZeneca, Servier, Novartis, Abbvie, Accord and Pfizer. RB reported personal fees from Accord, AstraZeneca, Daiichi-Sankyo, Eisai, Eli-Lilly, MSD, Novartis, Roche, Puma, Pierre-Fabre and Sandoz; grants from Daiichi-Sankyo, Novartis and Roche; non-financial support from Eli-Lilly and MSD. SDP reported personal fees from Roche, Novartis, Pfizer, Celgene, AstraZeneca and Eli-Lilly. VM reported funding to the institution from Novartis, Roche, Seattle Genetics and Genentech; personal fees from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva and Seattle Genetics; consultancy honoraria from Genomic Health, Hexal, Roche, Pierre-Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Eli-Lilly, Tesaro, Seattle Genetics and Nektar. J-PM reported personal fees from Roche, AstraZeneca, Bayer, Innate, Merck-Serono, Boeringher, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology and Pfizer; grant from BMS; travel fee from Amgen; other support from MSD, Psioxus, Debio and Nanobiotix. GJ reported personal fees from Novartis, Roche, Pfizer, Eli-Lilly, Amgen, BMS, AstraZeneca, Daiichi-Sankyo and Abbvie; grants from Novartis, Roche and Pfizer; non-financial support from Medimmune and Merck KGaA., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS)., Methods: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement., Results: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84)., Conclusion: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant., Patients and Methods: This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting., Results: From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33-83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1-7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4-58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%)., Conclusions: The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The aim of the present study was to evaluate the activity and tolerability of low-dose oral ethinylestradiol (EE) and luteinizing hormone-releasing hormone analogue with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent for advanced castrate-resistant prostate cancer (CRPC)., Patients and Methods: The patients received an EE dose of 150 μg daily (50 μg 3 times daily) and an ASA dose of 100 mg once daily. The primary endpoint was the prostate-specific antigen response., Results: A total of 32 patients were enrolled. A PSA response was observed in 19 patients (59.3%; 95% confidence interval [CI], 41%-76%). The median progression-free survival was 9.4 months (95% CI, 6.5-14.1 months). The treatment was generally well tolerated and no grade 3-4 toxicity was observed. Only 1 patient interrupted EE because of a cardiac event and 1 patient experienced grade 2 nausea and vomiting. No major bleeding occurred., Conclusion: Low-dose EE with concomitant low-dose ASA is safe, showing potential activity in patients with advanced CRPC, and should be investigated further., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB., Methods: In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND., Results: The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%)., Conclusion: Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2., Patients and Methods: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity., Results: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related., Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2., Clinical Trial Registration: EudraCT Number: 2012-000073-23., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Small cell lung cancer (SCLC) is a lethal disease with a very restricted armamentarium of active treatments. In the new era of targeted therapies, several attempts based on the combination of chemotherapy with new compounds has been made but with a low rate of success. The idea of using the new targeted therapies as maintenance treatment after their combination with chemotherapy has been pursued. The aim of the present study was to analyze the available clinical data regarding the effect of the targeted agents as maintenance therapy on survival in patients with SCLC. A literature-based meta-analysis of randomized controlled trials, in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines, was performed. PubMed, the Cochrane Library, and a search of abstracts presented at American Society of Clinical Oncology meetings were searched for relevant studies. The primary outcome was overall survival (OS). Nine studies, with a total of 1385 patients, were included. The pooled analysis revealed that the new targeted therapies did not improve survival compared with the control arm (placebo, hazard ratio, 1.02; 95% confidence interval, 0.91-1.15; P = .69). However, a small advantage in the 1-year OS rate (risk ratio, 1.21; 95% confidence interval, 0.9-1.63; P = .21) was observed. Maintenance with targeted therapies failed to improve the survival of patients with SCLC with an increased rate of toxicity. The detected survival advantage suggests that perhaps the maintenance approach could be used to increase the 1-year OS rate. However, this finding requires confirmation in further studies, perhaps of patients selected according to their tumor biologic profile., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The VERITAS (A Phase 1B open-label study to assess the safety and tolerability of everolimus in combination with eribulin in triple-negative breast cancers) trial (EudraCT number: 2014-000135-17) is a phase Ib, open label, multicenter, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study based on the combination of everolimus with eribulin in sequential cohorts of metastatic triple negative breast cancer (TNBC) patients., Patients and Methods: The primary objective of the study is to identify the recommended dose of everolimus in combination with eribulin. Secondary endpoints include the assessment of pharmacokinetics and antitumor activity of the experimental treatment. The sample size is based on the Bayesisan approach with regards to the maximum tolerated dose (MTD) and maximum tolerated dose (MTD) observed. An average sample size of approximately 12 patients is deemed reasonable based on simulations., Conclusion: The VERITAS trial is expected to determine the recommended dose of everolimus in combination with eribulin in TBNC. This study may open the way for further analysis of this combination in phase II studies in this orphan disease of active drug combination such as the TNBC subset., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: To measure the impact of MammaPrint on adjuvant treatment decisions and to analyze the agreement in treatment decisions between hospitals from 4 European countries for the same patient cohort., Methods: Breast cancer patients were prospectively enrolled and MammaPrint was assessed. Patients' clinical data without and then with MammaPrint results were sent to the different multidisciplinary teams and treatment advice was provided for each patient., Results: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian, 28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter-institutional agreement in treatment advice (chemotherapy or no chemotherapy) from 51% to 75%., Conclusion: The results of this study indicate that MammaPrint impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter-institutional and inter-country variability in adjuvant treatment advice for breast cancer patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pathologic complete response (pCR) was noted to be prognostic in all but hormone receptor-positive (HR) breast cancer cases even when HER2 is overexpressed. Evocative data suggest that HER2-positive breast cancer patients are a heterogeneous population and a subset of HER2-positive and HR-positive tumors biologically behave more like HER2-negative. Identification and targeted monitoring of these patients is crucial to consolidate data aiming to optimize combination treatment with new agents, thereby avoiding overtreatment with chemotherapy. The questions surrounding HER2-positive and HR-positive breast cancer patients treatment as well as the potential direction towards development of surrogate markers alternative to pCR are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Gene expression profiling tests are used in an attempt to determine the right treatment for the right person with early-stage breast cancer that may have spread to nearby lymph nodes but not to distant parts of the body. These new diagnostic approaches are designed to spare people who do not need additional treatment (adjuvant therapy) the side effects of unnecessary treatment, and allow people who may benefit from adjuvant therapy to receive it. In the present review we discuss in detail the major diagnostic tests available such as MammaPrint dx, Oncotype dx, PAM50, Mammostrat, IHC4, MapQuant DX, Theros-Breast Cancer Gene Expression Ratio Assay, and their potential clinical applications., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In this process, cells acquire molecular alterations that facilitate dysfunctional cell-cell adhesive interactions and junctions. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Such transformation has implications in progression of breast carcinoma to metastasis, and increasing evidences support most tumors contain a subpopulation of cells with stem-like and mesenchymal features that is resistant to chemotherapy. This review focuses on the physiological and pathological role of EMT process, its molecular related network, its putative role in the metastatic process and its implications in response/resistance to the current and/or new approaching drugs in the clinical management of breast cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(-) advanced breast cancer., Patients and Methods: Patients with HER2(-) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m(2) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. [corrected], Results: The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18-2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16-2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs., Conclusion: The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)