HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer

Background: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients’ outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems. Trial design: After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient’s medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment.Novartis and the non-profit organizations: Asociación Cáncer de Mama Metastásico and Fundación Actitud frente al Cáncer. F1CDxinitiative: Saray (Asociación Navarra de cáncer de mama); Federación Española de Cáncer de Mama (FECMAAsociación Vive, ni una estrella más and Manualitats Solidàries Cerdanyola. PfizerHOPE Run initiative whose benefits were invested in this tria

SEOM–GEICAM–SOLTI clinical guidelines in advanced breast cancer (2022)

Advanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer

NT-proBNP as predictor factor of cardiotoxicity during trastuzumab treatment in breast cancer patients

Background Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients. Methods We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age. Results 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2–28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7–85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity. Conclusion NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.Ramon Areces Foundation, Madrid, Spai

Oligometástasis en cáncer de mama: estrategias y perspectivas para el control local del tumor primario y de las metástasis

El cáncer de mama metastásico, identificado en el momento del diagnóstico o desarrollado tras transcurrir cierto tiempo desde la aparición de la enfermedad primaria, presenta una naturaleza heterogénea. Los resultados obtenidos gracias a los avances farmacológicos nos motivan a explorar la suplementación del tratamiento empleando técnicas de abordaje local. Esta revisión está dirigida a analizar la información disponible en la literatura sobre dos aspectos fundamentales en el cáncer de mama. Por un lado, el control del tumor primario, tanto en la mama como en los ganglios linfáticos locorregionales, y por otro, el control local de las metástasis en función de su localización en los casos de enfermedad oligometastásica. Las principales estrategias para llevar a cabo dicho control local son la cirugía, la radioterapia, incluyendo la radioterapia estereotáctica corporal o la radioterapia de haz externo, y la ablación por radiofrecuencia. Las evidencias discutidas señalan que, a la espera de más resultados procedentes de ensayos controlados aleatorios y de estudios específicos de la enfermedad, las pacientes con oligometástasis deben ser evaluadas por un equipo multidisciplinar. Las metástasis únicas podrían ser candidatas para tratamiento local, cada vez más eficiente, y esto, en combinación con los avances en la terapia sistémica, podría resultar en un mejor control de la enfermedad. Todas estas alternativas deberían presentarse a las pacientes con la finalidad de seleccionar un tratamiento personalizado, con base en la evidencia científica y en las características propias de su enfermedad, que presuponga un resultado más eficaz.Metastatic breast cancer, identified at the time of diagnosis or developed after a certain period since the onset of the primary disease, presents a heterogeneous nature. The results obtained through pharmacological advances encourage us to explore supplementing the treatment using local management techniques. This review aims to analyze the available literature on two fundamental aspects of breast cancer. On the one hand, the control of the primary tumor, both in the breast and in the locoregional lymph nodes, and on the other hand, the local control of metastases depending on their location in cases of oligometastatic disease. The main strategies for carrying out such local control are surgery, radiotherapy, including stereotactic body radiotherapy or external beam radiotherapy, and radiofrequency ablation. The evidence discussed indicates that, pending further results from randomized controlled trials and disease-specific studies, patients with oligometastasis should be evaluated by a multidisciplinary team. Single metastases could be candidates for local treatment, increasingly efficient, and this, in combination with advances in systemic therapy, could result in better disease control. All these alternatives should be presented to patients with the purpose of selecting a personalized treatment, based on scientific evidence and the unique characteristics of their disease, which presupposes a more effective outcome.AstraZenecaLillyPfizerRoch

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis

Objectives: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. Methods: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. Results: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). Conclusions: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile

Factores pronósticos en pacientes con cáncer de mama sin afectación ganglionar axilar

Tesis Univ. Granada. Departamento de Medicina. Leída el 5 de julio de 200

Early increase in tamoxifen dose in CYP2D6 poor metaboliser breast cancer patients and survival: A propensity score matching analysis

Purpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. Methods: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. Results: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. Conclusion: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.Consejería de Salud y Familias-Junta de Andalucía (PECART-0207-2020)Fundación Hospital Provincial de Castell´on, Centre for Industrial Technological Development (CDTI, IDI 20080842

Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells

Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.Consejería de Salud y Familias - Junta de Andalucía (PECART-0207-2020), the Junta de Andalucía - Universidad de Granada - European Regional Development Fund (B‐FQM‐278–UGR20), and the Ministerio de Economía y Competitividad (CTQ2014-56611-R)