Magnitude and Temporal Variations of Socioeconomic Inequalities in the Quality of Life After Early Breast Cancer: Results From the Multicentric French CANTO Cohort.

PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.

A budget impact analysis of a digital monitoring solution in patients treated with oral anticancer agents: a medico-economic analysis of the randomized phase 3 CAPRI trial.

BACKGROUND/OBJECTIVES: Remote patient monitoring (RPM) has demonstrated numerous benefits in cancer care, including improved quality of life, overall survival, and reduced medical resource use. This study presents a budget impact analysis of a nurse navigator-led RPM program, based on the CAPRI trial, from the perspective of the French national health insurance (NHI). The study aimed to assess the impact of the program on medical resource utilization and costs. METHODS: Medical resource utilization data were collected from both medico-administrative sources and patient-reported questionnaires. Costs were calculated by applying unit costs to resource utilization and estimating the average monthly cost per patient. Sensitivity analyses were conducted to explore different perspectives and varying resource consumption. RESULTS: The analysis included 559 cancer patients participating in the CAPRI program. From the NHI perspective, the program resulted in average savings of €377 per patient over the 4.58-month follow-up period, mainly due to reduced hospitalizations. The all-payers perspective yielded even greater savings of €504 per patient. Sensitivity analyses supported the robustness of the findings. CONCLUSION: The budget impact analysis demonstrated that the CAPRI RPM program was associated with cost savings from the perspective of the NHI. The program's positive impact on reducing hospitalizations outweighed the additional costs associated with remote monitoring. These findings highlight the potential economic benefits of implementing RPM programs in cancer care. Further research is warranted to assess the long-term cost-effectiveness and scalability of such programs in the real-world settings.

Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial.

The landscape of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance is still being elucidated and the optimal subsequent therapy to overcome resistance remains uncertain. Here we present the final results of a phase Ib/IIa, open-label trial (NCT02871791) of exemestane plus everolimus and palbociclib for CDK4/6i-resistant metastatic breast cancer. The primary objective of phase Ib was to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase II dose (100 mg palbociclib, 5 mg everolimus, 25 mg exemestane). The primary objective of phase IIa was to determine the clinical benefit rate (18.8%, n = 6/32), which did not meet the predefined endpoint (65%). Secondary objectives included pharmacokinetic profiling (phase Ib), objective response rate, disease control rate, duration of response, and progression free survival (phase IIa), and correlative multi-omics analysis to investigate biomarkers of resistance to CDK4/6i. All participants were female. Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial's therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.

Effectiveness of palbociclib with aromatase inhibitors for the treatment of advanced breast cancer in an exposure retrospective cohort study: implications for clinical practice.

BACKGROUND: New drugs for locally advanced or metastatic breast cancer have led to clinical benefits, aside with increasing costs to healthcare systems. The current financing model for health technology assessment (HTA) privileges real-world data. As part of the ongoing HTA, this study aimed to evaluate the effectiveness of palbociclib with aromatase inhibitors (AI) and compare it with the efficacy reported in PALOMA-2. METHODS: A population-based retrospective exposure cohort study was conducted including all patients initiating treatment in Portugal with palbociclib under early access use and registered in the National Oncology Registry. The primary outcome was progression free survival (PFS). Secondary outcomes considered included time to palbociclib failure (TPF), overall survival (OS), time to next treatment (TTNT), and proportion of patients discontinuing treatment due to  adverse events (AEs). The Kaplan-Meier method was used and median, 1- and 2-year survival rates were computed, with two-sided 95% confidence intervals (95%CI). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines for reporting observational studies were used. RESULTS: There were 131 patients included. Median follow-up was 28.3 months (IQR: 22.7-35.2) and median duration of treatment was 17.5 months (IQR: 7.8-29.1). Median PFS was 19.5 months (95%CI 14.2-24.2), corresponding to a 1-year PFS rate of 67.9% (95%CI 59.2-75.2) and a 2-year PFS rate of 42.0% (95%CI 33.5-50.3). Sensitivity analysis showed median PFS would increase slightly when excluding those not initiating treatment with the recommended dose, raising to 19.8 months (95%CI 14.4-28.9). By considering only patients meeting PALOMA-2 criteria, we could observe a major difference in treatment outcomes, with a mean PFS of 28.8 months (95%CI 19.4-36.0). TPF was 19.8 months (95%CI 14.2-24.9). Median OS was not reached. Median TTNT was 22.5 months (95%CI 18.0-29.8). A total of 14 patients discontinued palbociclib because of AEs (10.7%). CONCLUSIONS: Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2. However, when used outside of these eligibility criteria, namely in patients with less favorable prognosis (e.g., presence of visceral disease), the benefits are inferior, even though still favorable.

PET/CT in Patients with Breast Cancer Treated with Immunotherapy.

Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.

Hyaluronic acid production and purification techniques: a review.

Hyaluronic acid (HA) is an exopolysaccharide extracted from several sources such as rooster combs, umbilical cords and microorganisms. A system that controls temperature, agitation and aeration of bacterial cultures could make the HA production autonomous. Therefore, HA of microbial origin is set to take over alternative methods of production. Furthermore, the use of different nutrient sources in the culture medium and the purification stage applied in the process can cause physicochemical alterations on the bioproduct. For instance, structural modifications that change the molecular weight of HA may alter its elastic and viscoelastic properties. As a result, HA synthesized by microbes has applications in pharmacology, biotechnology, and tissue engineering. Our aim here, is to show the vast range of applications by compiling articles and patents on the culture media or genetic modifications of microorganisms that synthesize HA.

Reason for referrals to neurology: a community-based study in Brazil / Motivos de derivación a neurología: un estudio de base comunitaria en Brasil / Motivos de encaminhamentos para neurologia: um estudo de base comunitária no Brasil

Objective:to quantify the reasons for referrals of primary care physicians to neurology in Belo Horizonte, Brazil. Method:cross-sectional study evaluating referrals from Primary Care to the specialty of Neurology in Belo Horizonte, registered in the NOVO SISREG regulatory system, from March 2019 to July 2020. Neurologists or family physicians from the Regula Mais Brasil project, with experience in referral protocols for neurology, carried out the evaluation of the main diagnoses. Results:13,844 referrals to neurology were identified, with an average of 814.35 referrals per month. Headache, epilepsy and cerebrovascular disorders were the most common reasons, accounting for 55.5% of referrals. Other neurological conditions identified less frequently were parkinsonism, tremor, syncope and vertigo, responsible for 10.9% of referrals. Conclusion:most referrals did not prioritize only neurology expertise. It is possible that cultural aspects and the routine of physicians, health services and the community itself determined these referrals, raising awareness about the high demand, waiting time and possible clinical conditions that are soon ceasing to be managed by other specialties that also share these skills.

Objetivo:cuantificar los motivos de derivación de médicos de atención primaria a neurología en Belo Horizonte, Brasil. Método:estudio transversalque evaluó las derivaciones de la Atención Primaria a la especialidad de Neurología en Belo Horizonte, registradas en el sistema regulatorio NOVO SISREG, de marzo de 2019 a julio de 2020. Neurólogos o médicos de familia del proyecto Regula Mais Brasil, con experiencia en protocolos de derivación para neurología, realizó la evaluación de los principales diagnósticos. Resultados:se identificaron 13.844 derivaciones a neurología, con una media de 814,35 derivaciones al mes. La cefalea, la epilepsia y los trastornos cerebrovasculares fueron los motivos más frecuentes, representando el 55,5% de las derivaciones. Otras condiciones neurológicas identificadas con menor frecuencia fueron parkinsonismo, temblor, síncope y vértigo, responsables del 10,9% de las derivaciones. Conclusión: la mayoría de las referencias no priorizaron solo la experiencia en neurología. Es posible que los aspectos culturales y la rutina de los médicos, los servicios de salud y la propia comunidad determinaran estas derivaciones, concientizando sobre la alta demanda, tiempo de espera y posibles cuadros clínicos que pronto están dejando de ser manejados por otras especialidades que también comparten estas habilidades.

Objetivo:quantificar os motivos de encaminhamentos de médicos da Atenção Primária para neurologia em Belo Horizonte, Brasil. Método:estudo transversal com avaliação de encaminhamentos da Atenção Básica para especialidade de Neurologia em Belo Horizonte, registrados no sistema de regulação NOVO SISREG, no periodo de março de 2019 a julho de 2020. Neurologistas ou médicos de família do projeto Regula Mais Brasil, com experiência em protocolos de encaminhamentos para neurologia, realizaram a avaliação dos principais diagnósticos. Resultados:foram identificados 13.844 encaminhamentos para neurologia, com uma média de 814,35 encaminhamentos por mês. Cefaleia, epilepsia e distúrbios cerebrovasculares foram os motivos mais comuns, representando 55,5% dos encaminhamentos. Outras condições neurológicas identificadas em menor frequência foram o parkinsonismo, tremor, síncope e vertigem, responsáveispor 10,9% dos encaminhamentos. Conclusão:a maioria dos encaminhamentos não priorizou somente a expertise da neurologia. É possível que aspectos culturais e a rotina de médicos, serviços de saúde e da própria comunidade determinaram esses encaminhamentos, ascendendo alerta quanto a alta demanda, tempo de espera e possíveis condições clínicas que estão deixando de ser brevemente manejadas por outras especialidades que também compartilham dessas competências.

Targeted Axillary Dissection after Chemotherapy: Feasibility Study with Clip and Carbon Dye Tattoo - Neotarget Trial.

Background: Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. Methods: Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. Results: Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). Conclusions: The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study.

BACKGROUND: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). MATERIALS AND METHODS: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). RESULTS: A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08). CONCLUSION: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.

Use of mHealth to Increase Physical Activity Among Breast Cancer Survivors With Fatigue: Qualitative Exploration.

BACKGROUND: Physical activity has shown beneficial effects in the treatment of breast cancer fatigue; nevertheless, a significant portion of patients remain insufficiently physically active after breast cancer. Currently most patients have a smartphone, and therefore mobile health (mHealth) holds the promise of promoting health behavior uptake for many of them. OBJECTIVE: In this study, we explored representations, levers, and barriers to physical activity and mHealth interventions among inactive breast cancer patients with fatigue. METHODS: This was an exploratory, qualitative study including breast cancer patients from a French cancer center. A total of 4 focus groups were conducted with 9 patients; 2 independent groups of patients (groups A and B) were interviewed at 2 consecutive times (sessions 1 to 4), before and after their participation in a 2-week mHealth group experience consisting of (1) a competitive virtual exercise group activity (a fictitious world tour), (2) participation in a daily chat network, and (3) access to physical activity information and world tour classification feedback. We used a thematic content analysis. RESULTS: Several physical activity levers emerged including (1) physical factors such as perception of physical benefit and previous practice, (2) psychological factors such as motivation increased by provider recommendations, (3) social factors such as group practice, and (4) organizational factors including preplanning physical activity sessions. The main barriers to physical activity identified included late effects of cancer treatment, lack of motivation, and lack of time. The lack of familiarity with connected devices was perceived as the main barrier to the use of mHealth as a means to promote physical activity. The tested mHealth group challenge was associated with several positive representations including well-being and good habit promotion and being a motivational catalyzer. Following feedback, modifications were implemented into the mHealth challenge. CONCLUSIONS: mHealth-based, easily accessed group challenges were perceived as levers for the practice of physical activity in this population. mHealth-based group challenges should be explored as options to promote physical activity in a population with fatigue after breast cancer.

Breast cancer surgery with augmented reality.

INTRODUCTION: Innovations in 3D spatial technology and augmented reality imaging driven by digital high-tech industrial science have accelerated experimental advances in breast cancer imaging and the development of medical procedures aimed to reduce invasiveness. PRESENTATION OF CASE: A 57-year-old post-menopausal woman presented with screen-detected left-sided breast cancer. After undergoing all staging and pre-operative studies the patient was proposed for conservative breast surgery with tumor localization. During surgery, an experimental digital and non-invasive intra-operative localization method with augmented reality was compared with the standard pre-operative localization with carbon tattooing (institutional protocol). The breast surgeon wearing an augmented reality headset (Hololens) was able to visualize the tumor location projection inside the patient's left breast in the usual supine position. DISCUSSION: This work describes, to our knowledge, the first experimental test with a digital non-invasive method for intra-operative breast cancer localization using augmented reality to guide breast conservative surgery. In this case, a successful overlap of the previous standard pre-operative marks with carbon tattooing and tumor visualization inside the patient's breast with augmented reality was obtained. CONCLUSION: Breast cancer conservative guided surgery with augmented reality can pave the way for a digital non-invasive method for intra-operative tumor localization.

Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.

Association between pertuzumab-associated diarrhoea and rash and survival outcomes in patients with HER2-positive metastatic breast cancer: Exploratory analysis from the CLEOPATRA trial.

BACKGROUND: Skin rash and diarrhoea are known side-effects of pertuzumab. Studies with other anti-HER2 agents suggested that adverse events correlate with patient outcomes. In this exploratory cohort of patients with metastatic HER2-positive breast cancer included in the CLEOPATRA trial we evaluated the value of rash and diarrhoea as prognostic markers and as predictors of pertuzumab benefit. METHODS: This is a retrospective analysis of the multicenter, prospective, randomised CLEOPATRA trial. We defined two analytic cohorts: cohort 1 (C1) included patients from treatment initiation, and cohort 2 (C2) included patients after discontinuation of docetaxel. A landmark analysis was introduced to deal with immortal-time bias. Study endpoints were progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox proportional hazards models were used. RESULTS: Of the 808 patients and after application of the landmark analysis, C1 and C2 included 777 and 518 patients, respectively. In C1, rash occurred in 271 patients (34.9%) and diarrhoea in 470 (60.5%). Rash was prognostic for PFS and OS (C1: adjusted hazard ratio [aHR] = 0.66 [95% CI = 0.48-0.91], p = 0.010]; C2: aHR 0.52 [95% CI = 0.30-0.89], p = 0.018) in both cohorts, while diarrhoea was only prognostic for PFS in cohort 2 (aHR = 0.65 [95% CI = 0.46-0.91], p = 0.011). Rash and diarrhoea were not predictive of pertuzumab benefit (in terms of PFS/OS) in the two cohorts. CONCLUSIONS: In patients treated with pertuzumab, trastuzumab, and docetaxel, rash is prognostic whenever it occurs during treatment, while diarrhoea only has prognostic value when occurring after docetaxel discontinuation. However, neither rash nor diarrhoea predict pertuzumab benefit.

Silicone granuloma mimicking lymphatic metastases in a patient with breast cancer

Silicone breast implants are commonly used, even for reconstruction after mastectomy in malignant disease. In this setting, the presence of suspicious lymphadenopathy should be investigated, because it could represent disease progression. A case of a woman with left breast cancer (more than 20 years ago) and prosthesic reconstruction is reported. She developed a second breast cancer on the opposite side. During follow up, a suspicious lymphadenopathy was seen in the computed tomography scan, but the final diagnosis corresponded to a siliconoma. Silicone granuloma is a difficult diagnosis in these cases, but must be considered.

Body weight and return to work among survivors of early-stage breast cancer.

BACKGROUND: Many breast cancer (BC) survivors are employed at diagnosis and are expected to return to work after treatment. Among them, around 50% are overweight or obese. There are limited data about the impact of body weight on their ability to return to work. METHODS: We used data from CANcer TOxicity (NCT01993498), a prospective, multicentre cohort of women with stage I-III BC. Professionally active women who were ≥5 years younger than retirement age were identified. Multivariable logistic regression models examined associations of body mass index (BMI) at diagnosis and subsequent weight changes with non-return to work 2 years after diagnosis, adjusting for psychosocial, treatment and behavioural characteristics. RESULTS: Among 1869 women, 689 were overweight or obese. Overall, 398 patients (21.3%) had not returned to work 2 years after diagnosis. Non-return to work was more likely for overweight or obese than underweight or normal weight patients (adjusted OR (aOR) 1.32; 95% CI, 1.01 to 1.75; p=0.045). Weight loss (≥5%) was observed in 15.7% overweight or obese and 8.7% underweight or normal weight patients and was associated with significant increases in physical activity only among overweight or obese patients (mean change, +4.7 metabolic-equivalent-of-task-hour/week; 95% CI +1.9 to +7.5). Overweight or obese patients who lost weight were more likely to return to work compared with those who did not lose weight (aOR of non-return-to-work, 0.48; 95% CI 0.24 to 0.97, p=0.0418), whereas weight loss was associated with increased odds of non-return to work among underweight or normal weight women (aOR 2.07; 95% CI 1.20 to 3.56, p=0.0086) (pinteractionBMI×weight changes=0.0002). The continuous trend of weight gain on non-return to work was significant for overweight or obese patients (aOR for one-percent-unit difference, 1.03; 95% CI 1.01 to 1.06, p=0.030). CONCLUSIONS: Excess weight may be a barrier to return to work. Among overweight or obese BC survivors, weight loss was associated with higher rates of return to work, whereas further weight gain was associated with lower likelihood of return to work. Employment outcomes should be evaluated in randomised studies of weight management.

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis.

BACKGROUND: Several endocrine therapy (ET)-based treatments are available for patients with advanced breast cancer. We assessed the efficacy of different ET-based treatments in patients with hormone receptor-positive/HER2-negative advanced breast cancer with endocrine-sensitive or endocrine-resistant disease. METHODS: We searched Medline and Cochrane Central Register of Controlled Trials up to 15 October 2019 and abstracts from major conferences from 2016 to October 2019. We included phase II/III randomised trials, comparing ≥2 ET-based treatments. Progression-free survival (PFS) and overall survival (OS) were analysed by network meta-analyses using MTC Bayesian models based on both fixed-effect and random-effect models; relative treatment effects were measured as HRs and 95% credibility intervals (CrI). All statistical tests were two-sided. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this systematic review is registered in the PROSPERO database. RESULTS: 55 publications reporting on 32 trials (n=12 293 patients) were included. Regarding PFS in the endocrine sensitive setting (n=5200; 12 trials), the combination of cyclin-dependent kinases (CDK)4/6-inhibitors (CDK4/6i)+fulvestrant 500 mg (F500) was likely the most effective treatment (surface under the cumulative ranking curve (SUCRA)=97.3%), followed by CDK4/6i+aromatase inhibitor ±goserelin; there was no significant difference between them (HR 0.82; 95% CrI 0.54-1.25). Regarding OS (n=2157; five trials), the most effective treatment was probably CDK4/6i+F500 (SUCRA=97.3%); comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.63-0.95). Regarding PFS in the endocrine-resistant setting (n=6635; 20 trials), CDK4/6i+F500 was likely the most effective treatment (SUCRA=95.7%), followed by capivasertib+F500, without significant difference between them (HR 0.91; 95% CrI 0.60-1.36). For OS (n=4377; 11 trials), the most effective treatments were capivasertib+F500 (SUCRA=84.7%) and CDK4/6i+F500 (SUCRA=69.9%). Comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.67-0.89). CONCLUSIONS: CDK4/6i+F500 is likely the best treatment option in both endocrine-sensitive and endocrine-resistant diseases for PFS, and in endocrine-sensitive patients for OS. Concerning OS in endocrine-resistant patients, capivasertib+F500 and CDK4/6i+F500 are likely the best treatments. PROSPERO REGISTRATION NUMBER: CRD42018104628.

Clinical outcomes of patients with breast cancer relapsing after (neo)adjuvant trastuzumab and receiving trastuzumab rechallenge or lapatinib-based therapy: a multicentre retrospective cohort study.

BACKGROUND: In the prepertuzumab era, we evaluated the clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who underwent first-line trastuzumab-based or lapatinib-based therapy according to prior exposure to (neo)adjuvant trastuzumab. MATERIALS AND METHODS: In this multicentre retrospective cohort study conducted in 14 Italian centres of the Gruppo Italiano Mammella, consecutive patients undergoing first-line trastuzumab or lapatinib-based therapy were included. Analyses were performed according to the type of first-line therapy for metastatic disease (trastuzumab or lapatinib). Dichotomous clinical outcomes were analysed using logistic regression and time-to-event outcomes using Cox proportional hazard models controlling for relevant demographic, clinicopathological and therapy characteristics. RESULTS: Out of 450 patients included in the study, 416 (92%) received trastuzumab and 34 (7.5%) lapatinib. As compared with the trastuzumab cohort, more patients in the lapatinib cohort had a trastuzumab-free interval <1 month (37% vs 13.9%; p=0.017) and brain metastasis as first site of relapse (38.2% vs 9.4%; p<0.001). Among the 128 patients who relapsed after prior (neo)adjuvant trastuzumab, 101 (78.9%) received first-line trastuzumab and 27 (21.1%) first-line lapatinib. The following outcomes were observed with first-line lapatinib or trastuzumab, respectively: overall response rate 45.5% vs 61.3% (p=0.184), clinical benefit rate 68.2% vs 72.5% (p=0.691), median progression-free survival (PFS) 11.4 vs 12.0 months (p=0.814) and median overall survival (OS) 34.7 vs 48.2 months (p=0.722). In patients with brain metastasis as first site of relapse, median PFS was 12.2 vs 9.9 months (p=0.093) and median OS 33.7 vs 28.5 months (p=0.280), respectively. CONCLUSIONS: In patients with HER2-positive breast cancer relapsing after prior (neo)adjuvant trastuzumab, first-line treatment with trastuzumab or lapatinib was not associated with a significant difference in the clinical outcomes. A non-significant trend favouring the use of lapatinib was observed in patients with brain metastasis as the first site of relapse.

Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases.

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01-1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06-1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.