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Background: Proton-pump-inhibitors (PPIs) are frequently prescribed for the management of anticancer drug-related gastrointestinal symptoms. Palbociclib is a weak base with pH-dependent solubility and potential drug-drug interaction at the absorption level may affect clinical pharmacokinetics. The current study was aimed at investigating the effect of co-administration of PPIs and palbociclib on progression-free survival (PFS) in metastatic breast cancer (mBC) patients., Patients and Methods: Patients affected by estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, who were candidates for first-line treatment with palbociclib, were enrolled in this retrospective observational study. Patients were defined as 'no concomitant PPIs' if no PPIs were administered during palbociclib treatment, and as 'concomitant PPIs' if the administration of PPIs covered the entire or not less than two-thirds of treatment with palbociclib. All clinical interventions were made according to clinical practice., Results: A total of 112 patients were enrolled in the study; 56 belonged to the 'no concomitant PPIs' group and 56 to the 'concomitant PPIs' group. Seventy-one patients were endocrine-sensitive and received palbociclib and letrozole, and 43 were endocrine-resistant and were treated with palbociclib and fulvestrant. The most prescribed PPI was lansoprazole. Patients taking PPIs had a shorter PFS than those taking palbociclib and endocrine therapy alone (14.0 versus 37.9 months, P < 0.0001). Multivariate analysis confirmed concomitant PPIs as the only independent predictive factor for shorter PFS (P = 0.0002). PFS was significantly longer in estrogen-sensitive mBC with no concomitant PPIs compared with patients taking PPIs or estrogen-resistant patients, with and without PPIs (P < 0.0001). No correlation with adverse events was found when considering grade >2 hematological toxicities [Common Terminology Criteria for Adverse Events (CTCAE) scale]., Conclusions: The present study demonstrates that concomitant use of PPIs in mBC patients treated with palbociclib has a detrimental effect on PFS. Therefore, it is recommended to prescribe PPIs with caution in these patients, strictly adhering to the indications in the summary of product characteristics (RCP)., Competing Interests: Disclosure MDR received fees from Astellas, AstraZeneca, Celgene, Novartis, Pfizer, Bio-Rad, Janssen, Sanofi-Aventis, Roche, and Ipsen; CO declares fees from Novartis, Eisai, and Gentili; IM declares Advisory Board fees from Pfizer, Eli Lilly, Novartis, Roche, outside the submitted work; RD reports receiving speaker bureau/advisor’s fee from Ipsen, Novartis, Pfizer, Sanofi Genzyme, AstraZeneca, Janssen, Gilead, Lilly, Gilead, and EUSA Pharma. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The present analysis aims to evaluate the consequences of a 2-month interruption of mammographic screening on breast cancer (BC) stage at diagnosis and upfront treatments in a region of Northern Italy highly affected by the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) virus., Methods: This retrospective single-institution analysis compared the clinical pathological characteristics of BC diagnosed between May 2020 and July 2020, after a 2-month screening interruption, with BC diagnosed in the same trimester of 2019 when mammographic screening was regularly carried out., Results: The 2-month stop in mammographic screening produced a significant decrease in in situ BC diagnosis (-10.4%) and an increase in node-positive (+11.2%) and stage III BC (+10.3%). A major impact was on the subgroup of patients with BC at high proliferation rates. Among these, the rate of node-positive BC increased by 18.5% and stage III by 11.4%. In the subgroup of patients with low proliferation rates, a 9.3% increase in stage III tumors was observed, although node-positive tumors remained stable. Despite screening interruption, procedures to establish a definitive diagnosis and treatment start were subsequently carried out without delay., Conclusion: Our data showed an increase in node-positive and stage III BC after a 2-month stop in BC screening. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm and meet infection prevention requirements., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, particularly in triple negative breast cancer (TNBC) characterized by high cell proliferation, aggressive behavior, and chemo-resistance., Patients and Methods: This is an open-label, multicenter phase II study evaluating the combination of eribulin (0.88 mg/m 2 ) plus gemcitabine (1000 mg/m 2 ) on days 1 and 8 of a 21-day cycle as either first- or second-line treatment of locally advanced or metastatic TNBC. The primary endpoint was the objective response for evaluable patients. A prospective, molecular correlative study was carried out to assess the role of germinal BRCA pathogenic variants and single nucleotide polymorphisms (SNPs) in predicting efficacy and toxicity of the combination regimen., Results: From July 2013 to September 2016, 83 evaluable patients were enrolled. They received a median number of six cycles of treatment. An overall response rate (ORR) of 37.3% (31 patients) was observed, with a complete response rate of 2.4% and a partial response rate of 34.9%; the clinical benefit rate was 48.8%. With a median follow-up of 28.8 months, the median response duration was 6.6 months, the median progression-free survival (PFS) was 5.1 months, and the median overall survival (OS) was 14.5 months. The most common grade 3-4 adverse events were aminotransferase elevation (in 25% of the patients) and neutropenia (in 23.8%). Women with BRCA1/2 pathogenic variants were associated with worse ORR, PFS, and OS than BRCA1/2 wild-type carriers. CYP3A4 and FGD4 SNPs were associated with increased risk of liver toxicity. Three different SNPs in CDA∗2, RRM1, and CYP2C8 genes were significantly associated with poorer OS., Conclusions: The combination of eribulin and gemcitabine showed promising activity and a moderate toxicity profile in metastatic TNBC. BRCA status and pharmacogenetics tests may help identify patients with high probability of response with negligible toxicity., Eudract Number: 2012-003505-10., Competing Interests: Disclosure CZ reports grants, personal fees, and non-financial support from Roche; grants from Eisai; grants, personal fees, and non-financial support from Novartis; grants, personal fees, and non-financial support from AstraZeneca; grants, personal fees, and non-financial support from Pfizer; grants from PharmaMar; grants and personal fees from Amgen; grants and personal fees from Tesaro; personal fees from QuintilesIMS; grants from Pierre Fabre; grants from Istituto Gentili; grants from Takeda; grants from TEVA; grants from Medivation; grants from AbbVie; grants from Array BioPharma; grants from Morphotek; grants from Synthon; grants from Seattle Genetics; grants from Lilly, grants from Celgene, outside the submitted work. AF reports personal fees from Roche, personal fees from Novartis, personal fees from Pfizer, personal fees from Lilly, outside the submitted work. AS reports personal fees from Novartis, personal fees from Amgen, personal fees from Istituto Gentili, outside the submitted work. AR reports personal fees from Pfizer, personal fees from Novartis, personal fees from Eli Lilly, personal fees from Roche, outside the submitted work. FP reports personal fees from Novartis, personal fees from Pfizer, personal fees from Amgen, outside the submitted work. FM reports personal fees from Roche, personal fees from Novartis, personal fees from Pfizer, personal fees from Pierre Fabre, personal fees from Eli Lilly, personal fees from Daiichi Sankyo, personal fees from Astra Zeneca, outside the submitted work. AA reports grants and personal fees from BMS, grants from MSD, grants from Roche, grants from Astra Zeneca, grants from Eli Lilly, grants from Takeda, grants from Bayer, outside the submitted work. AM reports grants and other from Eisai Co., Ltd, during the conduct of the study; grants and personal fees from Roche; personal fees from MacroGenics; personal fees from Merck; grants and personal fees from Lilly; grants from Pfizer, outside the submitted work. All other authors have declared no conflicts of interest. Disclaimer Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO, Roche, or Eisai., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)