Search

Aim: This real-world study aimed to describe patient and clinical characteristics, treatment patterns and outcomes for patients with HR+/HER2- metastatic breast cancer receiving abemaciclib in France, Italy and Spain. Materials & methods: A multicenter chart review was conducted for adult females with HR+/HER2- advanced/metastatic breast cancer who received abemaciclib in routine care. Real-world progression-free survival (rwPFS) was estimated via Kaplan-Meier curves. Results: This study included 151, 173 and 175 patients from France, Italy and Spain, respectively. Abemaciclib was mostly prescribed as first-line therapy concomitantly with hormone therapy. Median rwPFS was >20 months and the 1-year rwPFS rate was >70%. Conclusion: Effectiveness was similar across the three countries and aligns with pivotal studies. Plain Language Summary Abemaciclib use in the clinic in France, Italy & Spain This study describes patients, the treatments they have received and the results of those treatments for patients with the most common type of advanced breast cancer. These patients were taking abemaciclib plus hormonal therapy in routine breast cancer care in France, Italy and Spain. The information used to conduct this study was taken from patients' medical charts. In this real-world study, abemaciclib was mostly used as the initial treatment for advanced breast cancer. Abemaciclib effectiveness was similar across the three countries confirming findings from previous studies. Our study supports the use of abemaciclib for patients with HR+/HER2- advanced breast cancer. Article highlights Patient & clinical characteristics Patients receiving abemaciclib in routine care in France, Italy and Spain were predominantly postmenopausal with a mean age of approximately 60 years. Breast cancer histological type at first diagnosis was predominantly nonspecific invasive carcinoma. Treatment patterns Abemaciclib was mostly prescribed in the first-line setting in combination with aromatase inhibitors or fulverstrant. Dosage Overall, most patients who initiated abemaciclib received a starting dose of 150 mg twice a day. Treatment discontinuation Range of discontinuation was between 45 and 55% across the three countries. Real world best tumor response & real-world progression free survival Real-world tumor response and rwPFS support the real-world use of abemaciclib for the treatment of HR+/HER2- advanced/metastatic breast cancer. Median rwPFS was ≥20 months for patients who received abemaciclib as first and second therapy lines across the three countries. Median rwPFS was highest for patients who received abemaciclib in the first-line setting. Healthcare resource utilization Levels of hospitalization remained low, and relatively constant, in the period immediately before treatment initiation and in the period after. Conclusion Our findings corroborate the effectiveness of real-world abemaciclib treatment for patients with advanced/metastatic breast cancer. [ABSTRACT FROM AUTHOR]

This study experimentally investigates boundary layer development over permeable interfaces using Hele-Shaw micromodels and high-resolution micro-particle image velocimetry (micro-PIV). Velocity vectors, captured at a 5 μ m scale, reveal the flow behavior at the interface between free-flow and porous media with ordered structures and porosities ranging from 50% to 85%. The results show that the boundary layer streamline alignment decreases with increasing porosity, while lower permeability fosters more uniform and parallel flow near the interface. Flow channeling occurs along paths of the least resistance, with more flow directed through the Hele-Shaw free-flow region as the solid fraction of the porous material increases. The Reynolds number (0.14–0.94), based on the Hele-Shaw hydraulic diameter, has a minimal effect on the normalized velocity distribution. Furthermore, an analytical solution for the external boundary layer thickness exhibited good agreement with experimental data, confirming a thickness of 2–4 times the square root of the free-flow Hele-Shaw permeability. Additionally, a Q-criterion analysis identified, for the first time, distinct zones within the external boundary layer, capturing the balance between rotational and deformation components as a function of permeability. These findings offer insight into flow dynamics in porous media systems, with implications for both natural and industrial applications, and contribute to the improved modeling of fluid dynamics and momentum transport in coupled free-flow and porous media environments. [ABSTRACT FROM AUTHOR]

The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65 years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60 mg via subcutaneous injection every 6 months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70 mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes. [ABSTRACT FROM AUTHOR]

The prevalence of malignant cells in clinical specimens, or tumour purity, is affected by both intrinsic biological factors and extrinsic sampling bias. Molecular characterization of large clinical cohorts is typically performed on bulk samples; data analysis and interpretation can be biased by tumour purity variability. Transcription-based strategies to estimate tumour purity have been proposed, but no breast cancer specific method is available yet. We interrogated over 6000 expression profiles from 10 breast cancer datasets to develop and validate a 9-gene Breast Cancer Purity Score (BCPS). BCPS outperformed existing methods for estimating tumour content. Adjusting transcriptomic profiles using the BCPS reduces sampling bias and aids data interpretation. BCPS-estimated tumour purity improved prognostication in luminal breast cancer, correlated with pathologic complete response in on-treatment biopsies from triple-negative breast cancer patients undergoing neoadjuvant treatment and effectively stratified the risk of relapse in HER2+ residual disease post-neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) is used in head and neck squamous cell carcinoma (HNSCC) with excellent effectiveness, but it is burdened by important side effects, which may negatively impact patients’ quality of life (QoL). In particular when associated with chemotherapy (CT), that has a radiosensitising effect (and its own toxicities), it is responsible for several adverse events, causing social discomfort and lower QoL, in patients who are already experiencing several tumor-related discomforts. Prehabilitation is a healthcare intervention consisting of several specialist visits prior to the start of treatment, with the aim of improving the patient’s health status, resolving symptoms that interfere with treatment and impact QoL, and finally to better avoid or overcome complications. Of all cancer patients, HNSCC patients are among those who could benefit most from prehabilitation, both because of the high number of symptoms and toxicities and their difficult management. Despite this and the emerging data, prehabilitation is not often considered for the majority of patients undergoing (C)RT. In this review, we tried to understand what are the main areas in which interventions can be made prior to the (C)RT start, the possible side effects of the treatment, the effectiveness in their prevention and management, and the impact that prehabilitation may have in adherence to therapy and on the principal survival outcomes, providing important guidance for the planning of future studies. Evidences and conclusions: Although there is no strong data evaluating multidisciplinary prehabilitation strategies, evidence shows that optimizing the patient’s health status and preventing possible complications improve the QoL, reduce the incidence and severity of adverse events, and improve treatment adherence. While cardiology prehabilitation is of paramount importance for all patients undergoing concomitant CRT in the prevention of possible side effects, the remaining interventions are useful independently of the type of treatment proposed. Geriatricians have a key role in both elderly patients and younger patients characterized by many comorbidities to comprehensively assess health status and indicate which treatment may be the best in terms of risk/benefit ratio. Collaboration between nutritionists and phoniatrics, on the other hand, ensures adequate nutritional intake for the patient, where possible orally. This is because optimizing both body weight and muscle mass and qualities has been shown to impact key survival outcomes. Finally, HNSCC patients have the second highest suicide rate, and the disease has side effects such as pain, dysfiguration, and sialorrhea that can reduce the patient’s social life and create shame and embarrassment: A psychological intake, in addition to the usefulness to the patient, can also provide current support to caregivers and family members. Therefore clinicians must define a personalized pathway for patients, considering the characteristics of the disease and the type of treatment proposed, to optimize health status and prevent possible side effects while also improving QoL and treatment adherence. [ABSTRACT FROM AUTHOR]

Objectives: To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death. Methods: One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected. Results: 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support. Conclusions: Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the most common oncological diseases among women in Western Countries and Italy as well. GIM 13-AMBRA is a patient journey study regarding how the prognosis of metastatic breast cancer patients has changed in the last decades as a result of the introduction of new drugs in clinical practice. This study also provides information regarding the different natural histories of breast cancer according to the presence or absence of hormone receptors and HER2 receptors. GIM 13-AMBRA is a longitudinal cohort study aimed at describing therapeutic strategies and the relative outcome parameters in 939 HER2-ve MBC patients. Taxanes–based regimens, or taxanes + targeted agents, mainly Bevacizumab, were the preferred first choice in both Luminal (30.2%) and TNBC (33.3%) patients. The median PFS1 was 12.5 months (95% CI 16.79–19.64), without any significant difference according to subtypes, while the median Time to first Treatment Change (TTC1) was significantly lower in TNBC patients (7.7 months—95% CI 5.7–9.2) in comparison to Luminal A (13.2 months, 95% CI 11.7–15.1) and Luminal B patients (11.8 months, 95% CI 10.3–12.8). PFS2 was significantly shorter in TNBC patients (5.5 months, 95% CI 4.3–6.5 vs. Luminal A—9.4, 95% CI 8.1–10.7, and Luminal B—7.7 95% CI 6.8–8.2, F-Ratio 4.30, p = 0.014). TTC2 was significantly lower in patients with TNBC than in those with the other two subtypes. The median OS1 was 35.2 months (95% CI 30.8–37.4) for Luminal A patients, which was significantly higher than that for both Luminal B (28.9 months, 95% CI 26.2–31.2) and TNBC (18.5 months, 95% CI 16–20.1, F-ratio 7.44, p = 0.0006). The GIM 13—AMBRA study is one of the largest collections ever published in Italy and provides useful results in terms of time outcomes for first, second, and further lines of treatment in HER2- MBC patients. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear1. Because ICB targets cell–cell interactions2, we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8+TCF1+T cells and MHCII+ cancer cells were dominant predictors of response, followed by cancer–immune interactions with B cells and granzyme B+ T cells. On-treatment, responsive tumours contained abundant granzyme B+ T cells, whereas resistant tumours were characterized by CD15+ cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology.Imaging mass cytometry is used to map the multicellular dynamics of immune checkpoint blockade-treated triple-negative breast cancer, finding that key proliferative fractions and cell–cell interactions drive response, and immunotherapy distinctively remodels tumour structure. [ABSTRACT FROM AUTHOR]

This paper validates the use of a harmonic analysis algorithm on a microcontroller to perform measurements of non-stationary signals in the context of smart grids. The increasing presence of electronic devices such as inverters of distributed generators (DG), power converters of charging stations for electric vehicles, etc. can drain non-stationary currents during their operation. A classical fast Fourier transform (FFT) algorithm may not have sufficient spectral resolution for the evaluation of harmonics and inter-harmonics. Thus, in this paper, the implementation of a chirp-Z transform (CZT) algorithm is suggested, which has a spectral resolution independent from the observation window. The CZT is implemented on a low-cost commercial microcontroller, and the absolute error is evaluated with respect to the same algorithm implemented in the LabVIEW environment. The results of the tests show that the CZT implementation on a low-cost microcontroller allows for accurate measurement results, demonstrating the feasibility of reliable harmonic analysis measurements even in non-stationary conditions on smart grids. [ABSTRACT FROM AUTHOR]

Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects. [ABSTRACT FROM AUTHOR]

Copyright of Climacteric is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Several models of genetic counseling have been proposed to tackle the increasing volume of individuals requiring access to BRCA testing. Few data are available on patient experience and retention of information with nurse‐driven genetic counseling. We evaluated the experience and retention of information in women with an uninformative BRCA test result and who were not considered at high risk due to their personal/family history of cancer who underwent geneticist‐supervised nurse‐driven genetic counseling and who received their test result by phone. Women who received an uninformative BRCA test result between May 2017 and September 2019 were administered a questionnaire exploring experience with genetic counseling and retention of information provided. Of 366 eligible women, 299 (273 breast cancer patients and 26 women without breast cancer) completed the interview. Overall, 280 women (93.6%) positively valued their experience with genetic counseling and 287 (96.0%) considered it helpful with 57.5% of them feeling reassured for themselves and their family. Information on the clinical implications of the test result was correctly retained and women acted accordingly. Overall, 252 women (87.8%) accurately reported their test result as normal/negative. Only 67 (22.4%) recognized that despite a normal BRCA test result, a low probability of a hereditary syndrome remains. Most women showed a poor ability to estimate cancer risk in BRCA mutation carriers and in the general population. Geneticist‐supervised nurse‐driven genetic counseling process for women with uninformative BRCA test result is associated with a positive patient experience and an adequate retention of information concerning the management of their personal and familial cancer risk. The design and implementation of nurse‐driven genetic counseling models may contribute to efficient and timely access to BRCA genetic testing. [ABSTRACT FROM AUTHOR]

Teenage pregnancy rates in the Peruvian Amazon are double the national average and among the highest in Latin America. Peruvian women living in rural, underserved and Amazon areas are more likely to become teenage mothers but the factors contributing to this socio-demographic trend are unclear. Thirty-one interviews and ethnographic observations of teenage and adult mothers living in the Peruvian Amazon were conducted to examine how social class and gender impacted their motherhood experiences. Despite preconceptions concerning the undesirability of teenage pregnancy, results show that teenage and adult mothers have similar experiences of motherhood. Both groups of women lack career and educational opportunities and are therefore economically dependent on men. This, combined with the cultural valorisation of motherhood, pushes them toward pregnancy and motherhood. In other words, pregnancy is a response to a lack of career and educational opportunities and not vice versa. The one difference found between teenage and adult mothers is that the former have less agency over reproductive decision making. In conclusion, motherhood among teenage and adult mothers in the Peruvian Amazon is an adaptive mechanism that gives women protection and fulfilment but is also the result of gender and class constraints that limit their life choices. [ABSTRACT FROM AUTHOR]

In patients with early-stage endocrine receptor-positive (ER+) breast cancer (BC), adjuvant endocrine therapy (ET) for 5 years is the standard of care. However, for some patients, the risk of recurrence remain high for up to 15 years after diagnosis and extended ET beyond 5 years may be a reasonable option. Nevertheless, this strategy significantly increases the occurrence of side effects. Here we summarize the available evidence from randomized clinical trials on the efficacy and safety profile of extended ET and discuss available clinical and genomic tools helpful to select eligible patients in daily clinical practice. [ABSTRACT FROM AUTHOR]

The use of an aromatase inhibitor (AI) in combination with ovarian function suppression (OFS) has become the mainstay of adjuvant endocrine therapy in high-risk premenopausal patients with hormone receptor-positive breast cancer. Although five years of such therapy effectively reduces recurrence rates, a substantial risk of late recurrence remains in this setting. Multiple trials have shown that extending AI treatment beyond five years could offer further protection. However, as these studies comprised only postmenopausal patients, no direct evidence currently exists to inform about the potential benefits and/or side effects of extended AI + OFS therapies in premenopausal women. Given these grey areas, we conducted a Delphi survey to report on the opinion of experts in breast cancer treatment and summarize a consensus on the discussed topics. A total of 44 items were identified, all centred around two main themes: 1) defining reliable prognostic factors to pinpoint premenopausal patients eligible for endocrine therapy extension; 2) designing how such therapy should optimally be administered in terms of treatment combinations and duration based on patients' menopausal status. Each item was separately discussed and anonymously voted by 12 experts representing oncological institutes spread across Italy. The consensus threshold was reached in 36 out of 44 items (82%). Herein, we discuss the levels of agreement/disagreement achieved by each item in relation to the current body of literature. In the absence of randomized trials to guide the tailoring of extended AI treatment in premenopausal women, conclusions from our study provide a framework to assist routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient-reported outcomes (PROs) and clinical outcomes among survivors of BC.Methods: The authors included survivors of stage I-III BC enrolled in the CANTO cohort (NCT01993498) that provided post-treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group-based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes.Results: Among 3788 patients, the authors identified four stable patterns of consumption: "Low" (25.8%), "Moderate" (37.6%), "High" (25.3%), and "Very high" (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the "Very high" group (vs. "Low"), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups.Conclusions: Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes. [ABSTRACT FROM AUTHOR]

The treatment of HR+/HER2- metastatic breast cancer with cyclin-dependent kinases 4 and 6 inhibitors combined with endocrine therapy has recently emerged as the most relevant therapeutic strategy. However, in routine clinical practice, the best therapeutic approach in patients with comorbidities at early relapsing or ab initio metastatic disease, PI3KCA mutation, is still debated among oncologists. Given these areas of uncertainty, we conducted a Delphi survey to describe and confront the level of agreement or disagreement between clinicians working in referral vs local spoke oncological hospitals and summarize a consensus on these debated topics. total, 56 items were drafted using the Nominal Group Technique and used for the Delphi Survey. A total of 46 clinicians participated in the survey. Overall, the consensus threshold among all participants was reached in 46/56 items (82%), and Delphi Survey results showed a high level of consensus. For the 10 items (18%) that did not reach the consensus threshold, possible explanations considering differences in clinical practice and recent findings from literature are provided in the Discussion. Outcomes from the present survey may help guide treatment in multiple comorbidities, early recurring and ab initio metastatic disease, and PI3KCA mutation, where evidence from randomized trials and level 1 evidence is currently missing. [ABSTRACT FROM AUTHOR]

Modern K-/Ka-band satellite communications have become increasingly demanding in recent years with regard to the performance of the terminal antenna used in the link. These terminals should be high gain and broadband, as well as guarantee polarization diversity over a large field of view. A low profile is also highly desired to integrate the antenna system into a variety of moving platforms, such as aircraft and trains. An ultra-low-profile continuous transverse stub array is proposed here to tackle these challenges. The antenna array is realized in printed circuit board technology by adopting a contactless transition between the stacked-up layers without resorting to blind or buried vias. The proposed antenna is wideband (impedance matched within the 19–31 GHz band, i.e., ~50%) and provides multibeam radiation for polar angles as far as ±22.5°. The peak value of the gain is 19.7 dBi, and the maximum radiation efficiency equals 50%. Furthermore, the antenna array is combined with a dual-band polarization converter. The latter provides orthogonal circular polarization (CP) in two non-adjacent bands. The overall antenna system performs right- and left-hand CPs within the SatCom downlink and uplink in the K-/Ka-band, respectively. For each polarization, the axial ratio is below 3 dB over 9.47% and 4.42% fractional bandwidths, respectively. [ABSTRACT FROM AUTHOR]

The study of circulating cancer-derived components (circulome) is considered the new frontier of liquid biopsy. Despite the recognized role of circulome biomarkers, their comparative molecular profiling is not yet routine. In advanced breast cancer (BC), approximately 40% of hormone-receptor-positive, HER2-negative BC cases harbor druggable PIK3CA mutations suitable for combined alpelisib/fulvestrant treatment. This pilot study investigates PIK3CA mutations in circulating tumor DNA (ctDNA), tumor cells (CTCs), and extracellular vesicles (EVs) with the aim of determining which information on molecular targetable profiling could be recollected in each of them. The in-depth molecular analysis of four BC patients demonstrated, as a proof-of-concept study, that it is possible to retrieve mutational information in the three components. Patient-specific PIK3CA mutations were found in both tissue and ctDNA and in 3/4 cases, as well as in CTCs, in the classical population (large-sized CD45−/EpCAM+/− cells), and/or in the "non-conventional" sub-population (smaller-sized CD44+/EpCAM−/CD45− cells). Consistent mutational profiles of EVs with CTCs suggest that they may have been released by CTCs. This preliminary evidence on the molecular content of the different circulating biomaterials suggests their possible function as a mirror of the intrinsic heterogeneity of BC. Moreover, this study demonstrates, through mutational assessment, the tumor origin of the different CTC sub-populations sustaining the translational value of the circulome for a more comprehensive picture of the disease. [ABSTRACT FROM AUTHOR]

Study Question: Is it safe to perform controlled ovarian stimulation (COS) for fertility preservation before starting anticancer therapies or ART after treatments in young breast cancer patients?Summary Answer: Performing COS before, or ART following anticancer treatment in young women with breast cancer does not seem to be associated with detrimental prognostic effect in terms of breast cancer recurrence, mortality or event-free survival (EFS).What Is Known Already: COS for oocyte/embryo cryopreservation before starting chemotherapy is standard of care for young women with breast cancer wishing to preserve fertility. However, some oncologists remain concerned on the safety of COS, particularly in patients with hormone-sensitive tumors, even when associated with aromatase inhibitors. Moreover, limited evidence exists on the safety of ART in breast cancer survivors for achieving pregnancy after the completion of anticancer treatments.Study Design, Size, Duration: The present systematic review and meta-analysis was carried out by three blinded investigators using the keywords 'breast cancer' and 'fertility preservation'; keywords were combined with Boolean operators. Eligible studies were identified by a systematic literature search of Medline, Web of Science, Embase and Cochrane library with no language or date restriction up to 30 June 2021.Participants/materials, Setting, Methods: To be included in this meta-analysis, eligible studies had to be case-control or cohort studies comparing survival outcomes of women who underwent COS or ART before or after breast cancer treatments compared to breast cancer patients not exposed to these strategies. Survival outcomes of interest were cancer recurrence rate, relapse rate, overall survival and number of deaths. Adjusted relative risk (RR) and hazard ratio (HR) with 95% CI were extracted. When the number of events for each group were available but the above measures were not reported, HRs were estimated using the Watkins and Bennett method. We excluded case reports or case series with <10 patients and studies without a control group of breast cancer patients who did not pursue COS or ART. Quality of data and risk of bias were assessed using the Newcastle-Ottawa Assessment Scale.Main Results and the Role Of Chance: A total of 1835 records were retrieved. After excluding ineligible publications, 15 studies were finally included in the present meta-analysis (n = 4643). Among them, 11 reported the outcomes of breast cancer patients who underwent COS for fertility preservation before starting chemotherapy, and 4 the safety of ART following anticancer treatment completion. Compared to women who did not receive fertility preservation at diagnosis (n = 2386), those who underwent COS (n = 1594) had reduced risk of recurrence (RR 0.58, 95% CI 0.46-0.73) and mortality (RR 0.54, 95% CI 0.38-0.76). No detrimental effect of COS on EFS was observed (HR 0.76, 95% CI 0.55-1.06). A similar trend of better outcomes in terms of EFS was observed in women with hormone-receptor-positive disease who underwent COS (HR 0.36, 95% CI 0.20-0.65). A reduced risk of recurrence was also observed in patients undergoing COS before neoadjuvant chemotherapy (RR 0.22, 95% CI 0.06-0.80). Compared to women not exposed to ART following completion of anticancer treatments (n = 540), those exposed to ART (n = 123) showed a tendency for better outcomes in terms of recurrence ratio (RR 0.34, 95% CI 0.17-0.70) and EFS (HR 0.43, 95% CI 0.17-1.11).Limitations, Reasons For Caution: This meta-analysis is based on abstracted data and most of the studies included are retrospective cohort studies. Not all studies had matching criteria between the study population and the controls, and these criteria often differed between the studies. Moreover, rate of recurrence is reported as a punctual event and it is not possible to establish when recurrences occurred and whether follow-up, which was shorter than 5 years in some of the included studies, is adequate to capture late recurrences.Wider Implications Of the Findings: Our results demonstrate that performing COS at diagnosis or ART following treatment completion does not seem to be associated with detrimental prognostic effect in young women with breast cancer, including among patients with hormone receptor-positive disease and those receiving neoadjuvant chemotherapy.Study Funding/competing Interest(s): Partially supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC; grant number MFAG 2020 ID 24698) and the Italian Ministry of Health-5 × 1000 funds 2017 (no grant number). M.L. acted as consultant for Roche, Pfizer, Novartis, Lilly, AstraZeneca, MSD, Exact Sciences, Gilead, Seagen and received speaker honoraria from Roche, Pfizer, Novartis, Lilly, Ipsen, Takeda, Libbs, Knight, Sandoz outside the submitted work. F.S. acted as consultant for Novartis, MSD, Sun Pharma, Philogen and Pierre Fabre and received speaker honoraria from Roche, Novartis, BMS, MSD, Merck, Sun Pharma, Sanofi and Pierre Fabre outside the submitted work. I.D. has acted as a consultant for Roche, has received research grants from Roche and Ferring, has received reagents for academic clinical trial from Roche diagnostics, speaker's fees from Novartis, and support for congresses from Theramex and Ferring outside the submitted work. L.D.M. reported honoraria from Roche, Novartis, Eli Lilly, MSD, Pfizer, Ipsen, Novartis and had an advisory role for Roche, Eli Lilly, Novartis, MSD, Genomic Health, Pierre Fabre, Daiichi Sankyo, Seagen, AstraZeneca, Eisai outside the submitted work. The other authors declare no conflict of interest. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of precision medicine, new tools for better management of breast cancer patients are still needed. From this perspective, circulating microRNA (miRNA), a small group of non-coding endogenous RNAs with a nucleotide length of 18–25, could be potentially appealing as diagnostic, prognostic and predictive biomarkers. miRNAs have been found to be deregulated in different pathological conditions including cancers. Moreover, due to their high stability in biological fluid, where they circulate freely or are associated with extracellular vesicles (EVs), they are ideal candidates to be used for non-invasive detection and monitoring. This review highlights the recent findings related to free and EV-derived miRNA applicability in breast cancer, pointing out the advantages, but also the issues, that still limit their translation in clinical practice. Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Human epidermal growth factor receptor 2 (HER2) positive breast cancer is a heterogeneous disease. Among different therapeutic approaches, immunotherapies represent a relevant option for HER2-positive breast cancer patients, both in the adjuvant and metastatic setting. Starting from the dramatic clinical improvement observed with the advent of trastuzumab, which embodied a partly immune-mediated mechanism, a new wave of immunotherapies is now under investigation, including the novel HER2-directed monoclonal antibodies, the antibody–drug conjugates, the immune checkpoint inhibitors, the adoptive T-cell therapies, and therapeutic vaccines. In this narrative review, we present the most important clinical evidence on immunotherapy in HER2-positive breast cancer, and we critically discuss the uncertainties and opportunities in this evolving field of immune-oncology. Breast cancer is the most common malignancy among women worldwide, and HER2-positive breast cancer accounts for approximately 15% of all breast cancer diagnoses. The advent of HER2-targeting therapies has dramatically improved the survival of these patients, significantly reducing their risk of recurrence and death. However, as a significant proportion of patients ultimately develop resistance to these therapies, it is extremely important to identify new treatments to further improve their clinical outcomes. Immunotherapy has revolutionized the treatment and history of several cancer types, and it has already been approved as a standard of care for patients with triple-negative breast cancer. Based on a strong preclinical rationale, immunotherapy in HER2-positive breast cancer represents an intriguing field that is currently under clinical investigation. There is a close interplay between HER2-targeting therapies (both approved and under investigation) and the immune system, and several new immunotherapeutic strategies, including immune checkpoint inhibitors, CAR-T cells and therapeutic vaccines, are being studied in this disease. In this narrative review, we discuss the clinical evidence and the future perspectives of immunotherapy for patients with HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background: Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor-positive disease. There are controversial data on its fertility preservation potential.Methods: The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients-Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.Results: Of 281 randomly assigned patients, 80.4% had hormone receptor-positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor-positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92).Conclusions: Final analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor-positive disease. [ABSTRACT FROM AUTHOR]

PURPOSE: The study of plasma cell-free DNA integrity (cfDI) has shown potential for providing useful information in neoplastic patients. The aim of this study is to estimate the accuracy of an electrophoresis-based method for cfDI evaluation in the assessment of pathologic complete response (pCR) in patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT). PATIENTS AND METHODS: Fifty-one patients with BC undergoing anthracycline-/taxane-based NACT were recruited. Plasma samples were collected from each patient at diagnosis (t0), after anthracycline administration (t1), and after NACT completion (t2). The concentration of differently sized cell-free DNA fragments was assessed by automated electrophoresis. cfDI, expressed as cfDI index, was calculated as the ratio of 321-1,000 bp sized fragment concentration to 150-220 bp sized fragment concentration assessed at t2. cfDI index was then used to build an exploratory classifier for BC response to NACT, directly comparing its sensitivity and specificity with magnetic resonance imaging (MRI), through bootstrapped logistic regression. RESULTS: cfDI index was assessed on 38 plasma samples collected from as many patients at t2, maintaining a 30/70 ratio between pCR and non-pCR patients. cfDI index showed an area under the receiver operating characteristic curve in predicting the achievement of pCR of 81.6, with a cutoff above 2.71 showing sensitivity = 81.8 and specificity = 81.5. The combination of cfDI index and MRI showed, in case of concordance, an area under the receiver operating characteristic curve of 92.6 with a predictive value of complete response of 87.5 and a predictive value of absence of complete response of 94.7. CONCLUSION: cfDI index measured after NACT completion shows great potential in the assessment of pCR in patients with BC. The evaluation of its use in combination with MRI is strongly warranted in prospective studies. Plasma DNA fragmentation assessment predicts response to neoadjuvant chemotherapy in breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. Methods: A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Results: Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12–1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15–2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80–1.77, p = 0.390). Conclusion: Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed. [ABSTRACT FROM AUTHOR]

Copyright of Themis: Revista de Derecho is the property of Themis Asociacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Offering ovarian function and/or fertility preservation strategies in premenopausal women with newly diagnosed breast cancer candidates to undergo chemotherapy is standard of care. However, few data are available on uptake and main reasons for refusing these options. Methods: The PREFER study (NCT02895165) is an observational, prospective study enrolling premenopausal women with early breast cancer, aged between 18 and 45 years, candidates to receive (neo)adjuvant chemotherapy. Primary objective is to collect information on acceptance rates and reasons for refusal of the proposed strategies for ovarian function and/or fertility preservation available in Italy. Results: At the study coordinating center, 223 patients were recruited between November 2012 and December 2020. Median age was 38 years (range 24 – 45 years) with 159 patients (71.3%) diagnosed at ≤40 years. Temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) was accepted by 58 out of 64 (90.6%) patients aged 41-45 years and by 151 out of 159 (95.0%) of those aged ≤40 years. Among patients aged ≤40 years, 57 (35.8%) accepted to access the fertility unit to receive a complete oncofertility counseling and 29 (18.2%) accepted to undergo a cryopreservation technique. Main reasons for refusal were fear of delaying the initiation of antineoplastic treatments and contraindications to the procedure or lack of interest in future childbearing. Patients with hormone-receptor positive breast cancer had a tendency for a higher acceptance rates of ovarian function and/or fertility preservation strategies than those with hormone-receptor negative disease. Conclusions: More than 90% of premenopausal women with early breast cancer, and particularly those with hormone receptor-positive disease, were concerned about the potential risk of chemotherapy-induced premature ovarian insufficiency and/or infertility and accepted GnRHa administration. Less than 1 out of 5 women aged ≤40 years accepted to undergo cryopreservation strategies. [ABSTRACT FROM AUTHOR]

Home birth is very common in the Peruvian Amazon. In rural areas of the Loreto region, home to indigenous populations such as the Kukama-Kukamiria, birth takes place at home constantly. This study aims to understand the preference for home births as well as childbirth and newborn care practices among Kukama-Kukamiria women in rural Loreto. Following a case study approach, sixty semi-structured, face-to-face interviews were conducted with recent mothers who experienced childbirth within one year prior to the interview, female relatives of recent mothers who had a role in childbirth, male relatives of recent mothers, community health workers, and traditional healers. We found that for women from these communities, home birth is a courageous act and an intimate (i.e. members of the community and relatives participate in it) and inexpensive practice in comparison with institutional birth. These preferences are also linked to experiences of mistreatment at health facilities, lack of cultural adaptation of birthing services, and access barriers to them. Preparations for home births included handwashing and cleaning delivery surfaces. After birth, waiting for the godparent to arrive to cut the cord can delay drying of the newborn. Discarding of colostrum, lack of skin-to-skin contact as well as a range of responses regarding immediate breastfeeding and immediate drying of the baby were also found. These findings were used to tailor the educational content of the Mamas del Rio program, where community health workers are trained to identify pregnancy early, perform home visits to pregnant women and newborns, and promote essential newborn care practices in case institutional birth is not desired or feasible. We make recommendations to improve Peru's cultural adaptation of birthing services. [ABSTRACT FROM AUTHOR]

Introduction: The prognosis of patients with HER2-positive early breast cancer has radically improved after the introduction of (neo)adjuvant anti-HER2 targeted therapy. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate combining the anticancer properties of the anti-HER2 agent trastuzumab and the antineoplastic cytotoxic drug DM1. After demonstrating to be an effective and safe treatment for patients with HER2-positive advanced breast cancer, the development of T-DM1 has moved to the early setting. Areas covered: The aim of this review is to explore the current role of T-DM1 in the treatment landscape of HER2-positive early breast cancer, focusing specifically on the efficacy and safety data available in the adjuvant setting. Expert opinion: T-DM1 is an effective and safe treatment option in the adjuvant setting for patients with HER2-positive breast cancer without pathologic complete response after standard neoadjuvant chemotherapy plus anti-HER2 targeted therapy. With the availability of more effective anti-HER2 targeted agents, including T-DM1, there is an urgent need for more chemotherapy de-escalation research efforts in the early setting. [ABSTRACT FROM AUTHOR]

PURPOSE To investigate the impact of the COVID-19 outbreak on the attitudes and practice of Italian oncologists toward breast cancer care and related research activities. METHODS A 29-question anonymous online survey was sent by e-mail to members of the Italian Association of Medical Oncology and the Italian Breast Cancer Study Group on April 3, 2020. Only medical oncologists (both those in training and specialists) were invited to complete the questionnaire. RESULTS Out of 165 responding oncologists, 121 (73.3.%) worked in breast units. In the (neo)adjuvant setting, compared with before the emergency, fewer oncologists adopted weekly paclitaxel (68.5% v 93.9%) and a dosedense schedule for anthracycline-based chemotherapy (43% v 58.8%) during the COVID-19 outbreak. In the metastatic setting, compared with before the emergency, fewer oncologists adopted first-line weekly paclitaxel for HER2-positive disease (41.8% v 53.9%) or CDK4/6 inhibitors for luminal tumors with less-aggressive characteristics (55.8% v 80.0%) during the COVID-19 outbreak. A significant change was also observed in delaying the timing for monitoring therapy with CDK4/6 inhibitors, assessing treatment response with imaging tests, and flushing central venous devices. Clinical research and scientific activities were reduced in 80.3% and 80.1% of respondents previously implicated in these activities, respectively. CONCLUSION Medical oncologists face many challenges in providing cancer care during the COVID-19 outbreak. Although most of the changes in their attitudes and practice were reasonable responses to the current health care emergency without expected major negative impact on patient outcomes, some potentially alarming signals of under treatment were observed. [ABSTRACT FROM AUTHOR]

Background: The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated. Methods: This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI). Results: A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87–1.16; P = 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24–0.32; P < 0.001). Similar results were observed in the secondary analysis including only breast cancer patients. Conclusions: These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers. [ABSTRACT FROM AUTHOR]

Background: During COVID‐19 outbreak, oncological care has been reorganized. Patients with cancer have been reported to experience a more severe COVID‐19 syndrome; moreover, there are concerns of a potential interference between immune checkpoint inhibitors (ICIs) and SARS‐CoV‐2 pathogenesis. Materials and methods: Between 6 and 16 May 2020, a 22‐item survey was sent to Italian physicians involved in administering ICIs. It aimed at exploring the perception about SARS‐CoV‐2‐related risks in cancer patients receiving ICIs, and the attitudes towards their management. Results: The 104 respondents had a median age of 35.5 years, 58.7% were females and 71.2% worked in Northern Italy. 47.1% of respondents argued a synergism between ICIs and SARS‐CoV‐2 pathogenesis leading to worse outcomes, but 97.1% would not deny an ICI only for the risk of infection. During COVID‐19 outbreak, to reduce hospital visits, 55.8% and 30.8% opted for the highest labelled dose of each ICI and/or, among different ICIs for the same indication, for the one with the longer interval between cycles, respectively. 53.8% of respondents suggested testing for SARS‐CoV‐2 every cancer patient candidate to ICIs. 71.2% declared to manage patients with onset of dyspnoea and cough as infected by SARS‐CoV‐2 until otherwise proven; however, 96.2% did not reduce the use of steroids to manage immune‐related toxicities. The administration of ICIs in specific situations for different cancer types has not been drastically conditioned. Conclusions: These results highlight the uncertainties around the perception of a potential interference between ICIs and COVID‐19, supporting the need of focused studies on this topic. [ABSTRACT FROM AUTHOR]

Copyright of Cuestiones de Filosofia is the property of Universidad Pedagogica y Tecnologica de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dose‐dense adjuvant chemotherapy is standard of care in high‐risk early breast cancer patients. However, its role in HER2‐positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we investigated the efficacy of dose‐dense chemotherapy in HER2‐positive breast cancer patients with or without exposure to trastuzumab. In the GIM2 trial, node‐positive early breast cancer patients were randomized to receive four cycles of (fluorouracil)epirubicin/cyclophosphamide followed by four cycles of paclitaxel administered every 2 (dose‐dense) or 3 (standard‐interval) weeks. After approval of adjuvant trastuzumab, protocol was amended in April 2006 to allow use of trastuzumab for 1 year after chemotherapy completion in HER2‐positive patients. The efficacy of dose‐dense chemotherapy in terms of disease‐free survival (DFS) and overall survival (OS) was assessed according to HER2 status and trastuzumab use. Out of 2,003 breast cancer patients, HER2 status was negative/unknown in 1,551 patients; among the 452 patients with HER2‐positive breast cancer, chemotherapy alone or followed by trastuzumab was given to 320 and 132 patients, respectively. Median follow‐up was 8.1 years. No significant interaction between HER2 status, trastuzumab use and chemotherapy treatment was observed for both DFS (p = 0.698) and OS (p = 0.708). Nevertheless, there was no apparent benefit in the HER2‐positive group treated with trastuzumab (DFS: HR, 0.99; 95% CI 0.52–1.89; OS: HR, 0.95; 95% CI 0.37–2.41). Although dose‐dense chemotherapy was associated with a significant survival improvement in high‐risk breast cancer patients, its benefit appeared to be smaller (if any) in patients with HER2‐positive disease who received adjuvant trastuzumab. What's new? Dose‐dense chemotherapy is standard of care in high‐risk early breast cancer; however, its role in HER2‐positive patients is still uncertain. In this exploratory analysis of the GIM2 trial, we showed that the benefit of dose‐dense chemotherapy appeared to be small (if any) in HER2‐positive patients who received trastuzumab raising concerns on the need of chemotherapy escalation approaches in this setting. These findings may guide the choice of adjuvant chemotherapy in HER2‐positive early breast cancer patients. [ABSTRACT FROM AUTHOR]

This article presents an efficient analysis method for a novel continuous transverse stub (CTS) antenna. As opposed to state-of-the-art CTS antenna designs, the proposed architecture achieves circular polarization using a single CTS array and without any polarization converter. The structure consists of long radiating slots/stubs fed by over-moded parallel-plate waveguides. More precisely, the transverse electromagnetic (TEM) mode and the first transverse electric (TE1) mode of the feeding waveguides are used to generate a circularly polarized field. The array is analyzed using a spectral mode-matching method. First, the active reflection coefficient of the infinite array is derived in closed form. A windowing approach is then adopted to compute the radiation patterns of finite-size arrays. Numerical results obtained with this method are in excellent agreement with full-wave simulations, carried out with a commercial software. The performance of this class of CTS antennas has been investigated using the developed model. It is theoretically demonstrated that the proposed array can be designed to attain an axial ratio (AR) lower than 3 dB over a 52.9% relative bandwidth at broadside. Furthermore, the active input reflection coefficient is lower than −10 dB over a 40.8% relative bandwidth, when the array steers its main beam at $\theta _{0}=45^\circ $. This solution is an attractive candidate for next generation satellite communication terminals. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy is the standard of care in high-risk early breast cancer patients. Dose-dense should be the preferred schedule of administration. However, its long-term benefit is unknown.Methods: In the Italian multicentre Phase 3 randomised MIG-1 trial, node-positive and high-risk node- negative breast cancer patients were randomised to receive six cycles of adjuvant fluorouracil, epirubicin and cyclophosphamide regimen administered every 3 (FEC21) or 2 (FEC14) weeks. The primary endpoint was overall survival (OS), and the secondary endpoint was event-free survival (EFS).Results: From 1992 to 1997, 1214 patients were included. Median follow-up was 15.8 years. In all, 15-year OS was 71% and 68% in the FEC14 and FEC21 groups, respectively (HR = 0.89; p = 0.25). In all, 15-year EFS was 47% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.87; p = 0.18). In a pre-planned subgroup analysis, among patients with hormone receptor-negative tumours, 15-year OS was 70% and 65% in the FEC14 and FEC21 groups, respectively (HR = 0.73; 95% CI: 0.51-1.06); 15-year EFS was 58% and 43% in the FEC14 and FEC21 groups, respectively (HR = 0.70; 95% CI: 0.51-0.96).Conclusions: Updated results from the MIG-1 study are numerically in favour of dose-dense chemotherapy, and suggest a long-term benefit of this approach in high-risk early breast cancer patients. [ABSTRACT FROM AUTHOR]

Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation. [ABSTRACT FROM AUTHOR]

Copyright of Studia Koszalinsko-Kolobrzeskie is the property of University of Szczecin Press / Wydawnictwo Naukowe Uniwersytetu Szczecinskiego and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)