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Introduction: Elacestrant has shown significantly prolonged progression-free survival compared to standard-of-care endocrine therapy in estrogen receptor-positive (ER-positive), HER2-negative metastatic breast cancer (BC), while potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early BC., Methods: Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative BC with locally assessed Ki67≥10% received elacestrant at a daily dose of 345mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest (CCCA), defined as Ki67≤2.7%, at day 28., Results: Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a CCCA rate of 27.3% and a statistically significant geometric mean change of -52.9% (p=0.007; 95%CI, -67.4 to -32.1). The treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, CD8A) and suppressed proliferation and estrogen-signaling (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression at day 28. Most common adverse events were grade 1: anemia (21.7%), hot flushes, constipation and abdominal pain (8.7%, each). One patient experienced a grade 3 cutaneous rash leading to treatment discontinuation. No other serious adverse events were reported., Conclusions: Preoperative treatment with elacestrant in early BC demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting.

Purpose: To comprehensively synthesize the existing evidence concerning mHealth interventions for patients with breast cancer (BC)., Design: On July 30, 2023, we searched PubMed, PsycINFO, and Google Scholar for articles using the following inclusion criteria: evaluation of mHealth interventions in patients with cancer, at least 30 participants with BC, randomized control trials or prospective pre-post studies, determinants of health (patient-reported outcomes [PROs] and quality of life [QoL]) as primary outcomes, interventions lasting at least 8 weeks, publication after January 2015. Publications were excluded if they evaluated telehealth or used web-based software for desktop devices only. The quality of the included studies was analyzed with the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies., Results: We included 30 studies (20 focused on BC), encompassing 5,691 patients with cancer (median 113, IQR, 135.5). Among these, 3,606 had BC (median 99, IQR, 75). All studies contained multiple interventions, including physical activity, tailored information for self-management of the disease, and symptom tracker. Interventions showed better results on self-efficacy (3/3), QoL (10/14), and physical activity (5/7). Lifestyle programs (3/3), expert consulting (4/4), and tailored information (10/11) yielded the best results. Apps with interactive support had a higher rate of positive findings, while interventions targeted to survivors showed worse results. mHealth tools were not available to the public in most of the studies (17/30)., Conclusion: mHealth interventions yielded heterogeneous results on different outcomes. Identifying lack of evidence on clinical scenarios (eg, patients undergoing systemic therapy other than chemotherapy) could aid in refining strategic planning for forthcoming research endeavors within this field.

Purpose: Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy., Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model., Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms., Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: In hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC), it is imperative to identify patients who respond poorly to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting, but further validation is needed., Experimental Design: We performed mRNA gene expression profiling and correlation with progression-free survival (PFS) on 455 tumor samples included in the phase III PEARL study, which assigned patients with HR+/HER2- MBC to receive palbociclib+endocrine therapy (ET) versus capecitabine. Estrogen receptor-positive (ER+)/HER2- breast cancer cell lines were used to generate and characterize resistance to palbociclib+ET., Results: Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4 months with palbociclib+ET and 9.3 months with capecitabine; HR 4.16, adjusted P value < 0.0001. Tumors with high CCNE1 expression (above median) also had worse median PFS with palbociclib+ET (6.2 months) than with capecitabine (9.3 months); HR 1.55, adjusted P value = 0.0036. In patients refractory to palbociclib+ET (PFS in the lower quartile), we found higher levels of Polo-like kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclib+ET treatment. In ER+/HER2- cell line models, we show that PLK1 inhibition reverses resistance to palbociclib+ET., Conclusions: We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: There is an increasing need to integrate patient-generated health data (PGHD) into health information systems (HISs). The use of health information standards based on the dual model allows the achievement of semantic interoperability among systems. Although there is evidence in the use of the Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources (SMART on FHIR) framework for standardized communication between mobile apps and electronic health records (EHRs), the use of European Norm/International Organization for Standardization (EN/ISO) 13606 has not been explored yet, despite some advantages over FHIR in terms of modeling and formalization of clinical knowledge, as well as flexibility in the creation of new concepts., Objective: This study aims to design and implement a methodology based on the dual-model paradigm to communicate clinical information between a patient mobile app (Xemio Research) and an institutional ontology-based clinical repository (OntoCR) without loss of meaning., Methods: This paper is framed within Artificial intelligence Supporting CAncer Patients across Europe (ASCAPE), a project that aims to use artificial intelligence (AI)/machine learning (ML) mechanisms to support cancer patients' health status and quality of life (QoL). First, the variables "side effect" and "daily steps" were defined and represented with EN/ISO 13606 archetypes. Next, ontologies that model archetyped concepts and map them to the standard were created and uploaded to OntoCR, where they were ready to receive instantiated patient data. Xemio Research used a conversion module in the ASCAPE Local Edge to transform data entered into the app to create EN/ISO 13606 extracts, which were sent to an Application Programming Interface (API) in OntoCR that maps each element in the normalized XML files to its corresponding location in the ontology. This way, instantiated data of patients are stored in the clinical repository., Results: Between December 22, 2020, and April 4, 2022, 1100 extracts of 47 patients were successfully communicated (234/1100, 21.3%, extracts of side effects and 866/1100, 78.7%, extracts of daily activity). Furthermore, the creation of EN/ISO 13606-standardized archetypes allows the reuse of clinical information regarding daily activity and side effects, while with the creation of ontologies, we extended the knowledge representation of our clinical repository., Conclusions: Health information interoperability is one of the requirements for continuity of health care. The dual model allows the separation of knowledge and information in HISs. EN/ISO 13606 was chosen for this project because of the operational mechanisms it offers for data exchange, as well as its flexibility for modeling knowledge and creating new concepts. To the best of our knowledge, this is the first experience reported in the literature of effective communication of EN/ISO 13606 EHR extracts between a patient mobile app and an institutional clinical repository using a scalable standard-agnostic methodology that can be applied to other projects, data sources, and institutions., (©Santiago Frid, Maria Angeles Fuentes Expósito, Inmaculada Grau-Corral, Clara Amat-Fernandez, Montserrat Muñoz Mateu, Xavier Pastor Duran, Raimundo Lozano-Rubí. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 12.10.2022.)

Aims: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB., Methods: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit., Results: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm., Conclusions: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases., Clinical Trial Registration: NCT02614794., Competing Interests: Conflict of interest statement V.M. reports consultancy for Amgen, AstraZeneca, ClinSol, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MSD Oncology, Novartis, Pierre Fabre, Roche, Seagen, Tesaro and Teva and research funding/grants from Novartis, Roche/Genentech and Seagen. A.W. reports corporate board membership for Andrew Wardley Limited, Manchester Cancer Academy and Outreach Research & Innovation Group Limited; consultancy for Accord Research, AstraZeneca, Athenex, Coleman Expert Network, Coleman Research, Daiichi Sankyo, Gerson Lehrman Group, Guidepoint Global, Lilly, MSD Oncology, NAPP Pharmaceuticals, Novartis, Pfizer and Roche; employment at the Christie NHS Foundation Trust and AstraZeneca (as of 11th January 2021); patents and royalties for Outreach Research & Innovation Group; speaker's bureau participation for AstraZeneca, Eisai, Lilly, Novartis, Pfizer and Roche; travel expenses from Daiichi Sankyo, MSD and Roche and other nonfinancial relationships with the Strategy Director for the Association of Cancer Physicians, Committee Member UK Breast Cancer Group, Committee Member NHS England and Chemo Clinical Reference Group, ESMO Breast Cancer Faculty and NCRI Breast Research Group Chair. E.P. reports consultancy for Mylan, Novartis, Pfizer and R-Pharm; research funding/grants from AbbVie, Cascadian, Corcept Therapeutics, Genentech, Hoosier Cancer Research Network, Merck, Novartis and Seagen and travel expenses from Amgen, Genentech, Merck, Novartis and Tesaro. E.H. reports consultancy for AstraZeneca, Black Diamond Therapeutics, Boehringer Ingelheim, Daiichi Sankyo, Genentech/Roche, Lilly, Mersana, Novartis, Pfizer, Puma Biotechnology and Silverback Therapeutics; research funding/grants from AbbVie, AceraPharma, Aravive, ArQule, Arvinas, AstraZeneca, BerGenBio, Black Diamond Therapeutics, Boehringer, Clovis Oncology, Compugen, Curis, CytomX Therapeutics, Daiichi Sankyo, Deciphera, eFFECTOR, Eisai, EMD Serono, Fochon Pharmaceuticals, Fosun Orinove, Fujifilm, G1 Therapeutics, Pfizer, Puma Biotechnology, Radius Health, Regeneron, Rgenix, Seagen, Sermonix Pharmaceuticals, Silverback Therapeutics, Stemcentrx, Sutro Biopharma, Syndax, Syros Pharmaceuticals, Taiho Pharmaceutical, Takeda, TapImmune, Tesaro, Torque, Unum Therapeutics, Verastem, Zenith Epigenetics, Zymeworks, Genentech/Roche, H3 Biomedicine, Harpoon, Hutchison MediPharma, Immunogenics, InventisBio, Karyopharm Therapeutics, Leap Therapeutics, Lilly, Lycera, MacroGenics, MedImmune, Medivation, Mersana, Merus, Millennium, Molecular Templates, Novartis, NuCana and OncoMed and travel expenses from Amgen, AstraZeneca, Bayer, BMS, Clovis, Eisai, EMD Serono, Foundation Medicine, Genentech/Roche, Genentech, Genzyme, Guardant Health, Helsinn Therapeutics, Heron, Lilly, Medivation, Merck, Novartis, Pfizer, Roche, Sysmex and Tesaro. A.Z. reports consultancy for Norvatis and Pfizer and travel expenses from Immunomedics. E.J. reports consultancy for Lilly, Novartis, Pfizer and Roche. F.B. reports consultancy and honoraria from Lilly, Novartis, Lilly and Roche and travel expenses from Novartis. E.H.B. reports travel expenses from Pierre Fabre, Pfizer and Roche. A.B. reports corporate board membership for NanoTx Therapeutics; consultancy for AlaMab Therapeutics, NanoTx Therapeutics, Plus Therapeutics and Vascular Biogenics; equity ownership in NanoTx and Plus Therapeutics; honoraria from Vascular Biogenics; patents and royalties related to intellectual property interest in NanoTx Therapeutics; research funding/grants from Boston Biomedical, Immunomedics, Medicenna, Mirna Therapeutics, Threshold Pharmaceuticals, Upsher-Smith and Vascular Biogenics and travel expenses from Vascular Biogenics. L.C. reports speaker's bureau participation for Astellas, Ipsen and Janssen and other fees for Astellas, Bristol Myers Squibb, Ipsen, Novartis and Pfizer. C.F. reports honoraria from Pfizer, Bayer, Novartis, AstraZeneca, Merck, Astellas Pharma and Roche Canada; a consulting or advisory role for Genomic Health, Merck, AstraZeneca, Bayer and Odonate Therapeutics; speaker's bureau for Merck; research funding/grants to self from Bayer; research funding/grant to the institution from Astellas Pharma, AstraZeneca, Lilly, Merck, Novartis, Roche/Genentech, Sanofi, Pfizer, Janssen Oncology, Zymeworks, Seagen, Immunomedics, Bicycle Therapeutics and Sermonix Pharmaceuticals and travel expenses from Novartis and Roche. M.M.-M. reports advisory board membership for Pierre Fabre; grants for conference attendance from Roche, Pfizer and Lilly and expert testimony for Novartis, Roche and Eisai. H.T.A. reports advisory board membership for Bayer, BeiGene, Bicycle, BioNTech, iOnctura, Roche and Servier and employment at HCA Healthcare UK and Sarah Cannon. N.I. reports consultancy for Janssen, Merck, Novartis and Pfizer. S.A. reports speaker's bureau participation for Novartis, Pfizer, Puma, Daiichi/AstraZeneca, Merck and Seagen. M.C. reports consultancy for Sanofi and travel expenses from Novartis, Bristol Myers Squibb and Ipsen. T.P. reports research funding/grants from Merck, Pfizer and Seagen. E.S.-R. reports consultancy for Lilly and Mylan, research funding/grants from Susan G. Komen Victory Foundation and speaker's bureau participation for Mylan. D.C. reports consultancy for Daiichi Sankyo, GlaxoSmithKline, Novartis, Roche and Synthon; employment at Edinburgh Cancer Research Centre, Edinburgh, United Kingdom and research funding/grants from Daiichi Sankyo, GlaxoSmithKline, Novartis, Roche and Seagen (all funding is to his institution). G.C. reports consultancy from Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche, Seagen and Daiichi Sankyo; employment at the University of Milano, Istituto Europeo di Oncologia, IRCCS, Milano, Italy and speaker's bureau participation for Lilly, Pfizer, Roche, Seagen and Daiichi Sankyo. K.G. reports consultancy for AstraZeneca, Bristol Myers Squibb, Genentech, Genomic Health, Janssen, Lilly, Merck, Mylan, NanoString, Novartis, Pfizer and Roche and research funding/grants from AstraZeneca, Bristol Myers Squibb, Pfizer and Roche. M.S. reports employment at Seagen Inc. and equity ownership in Seagen Inc. and Moderna Pharma. K.D. reports employment at Seagen Inc. and equity ownership in Seagen Inc. and Roche. J.R. and W.F. report employment at Seagen Inc. and equity ownership in Seagen Inc. M.B., S.C., M.C., E.C., L.F. and O.H. have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC., Patients and Methods: Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m(2), respectively, × four cycles), followed by docetaxel (100 mg/m(2) × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m(2), respectively, × four cycles), followed by capecitabine (1,250 mg/m(2) twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS)., Results: After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months)., Conclusion: Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms., (© 2015 by American Society of Clinical Oncology.)

Purpose: Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established., Patients and Methods: Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival., Results: After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%)., Conclusion: For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.

The incidence is increasing due to mammographic screening and an ageing population. In some countries the mortality rate has decreased especially in middleaged and younger groups because of improved treatment and possibly earlier detection. However, breast cancer is still the leading cause of cancer-related death in European women. The purpose of this work was to elaborate a Spanish Society of Medical Oncology guideline on pharmacologic interventions for early breast cancer (BC). We have compiled the latest advances in the management of this pathology either in the adjuvant and neoadjuvant setting, cytostatic and hormonal treatment, so that in a simple way could be useful to oncologist, residents and other related specialties.