Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study.

Molecular signatures to guide decisions for adjuvant chemotherapy are recommended in early ER-positive, HER2-negative breast cancer. The objective of this study was to assess what impact gene-expression-based risk testing has had following its recommendation by Swedish national guidelines. Postmenopausal women with ER-positive, HER2-negative and node negative breast cancer at intermediate clinical risk and eligible for chemotherapy were identified retrospectively from five Swedish hospitals. Tumor characteristics, results from Prosigna® test and final treatment decision were available for all patients. Treatment recommendations were compared with the last version of regional guidelines before the introduction of routine risk signature testing. Among the 360 included patients, 41% (n = 148) had a change in decision for adjuvant treatment based on Prosigna® test result. Out of the patients with clinical indication for adjuvant chemotherapy, 52% (n = 118) could avoid treatment based on results from Prosigna® test. On the contrary, 23% (n = 30) of the patients with no indication were escalated to receive adjuvant chemotherapy after testing. Ki67 could not distinguish between the Prosigna® risk groups or intrinsic subtypes and did not significantly differ between patients in which decision for adjuvant therapy was changed based on the test results. In conclusion, we report the first real-world data from implementation of gene-expression-based risk assessment in a Swedish context, which may facilitate the optimization of future versions of the national guidelines.

Women with short survival after diagnosis of metastatic breast cancer: a population-based registry study.

PURPOSE: Despite therapeutic advances, overall survival of metastatic breast cancer (MBC) at the population level has seen little improvement over the past decades. Aggressive tumor biology or delay in access to cancer care might be contributing factors. With this retrospective population-based study we aimed to quantify and characterize patients with very short survival time following MBC diagnosis. METHODS: Women diagnosed with MBC between Jan 1st, 2005 and Dec 31st, 2016 were identified using the population-based Stockholm-Gotland breast cancer registry. Data regarding demographic and clinicopathological characteristics, survival, and treatment were extracted retrospectively from the registry and from patient charts. Patients who died within 90 days following diagnosis of MBC were identified and their characteristics were compared with all other patients diagnosed with MBC during the same period. RESULTS: Between 2005 and 2016, 3124 patients were diagnosed with MBC, of whom 498 (16.2%) died within 90 days of diagnosis. Nearly half (N = 233) did not receive any antitumoral treatment. Patients with short survival were older (p < 0.001), had higher primary tumor grade (p < 0.001), higher clinical stage at primary diagnosis (p = 0.002), and more often estrogen receptor (ER)-negative breast cancer (p < 0.001). Visceral metastases were more frequent (p < 0.001) and patients with short survival received adjuvant chemotherapy (p < 0.001) to a lesser extent compared to patients with a better prognosis. In multivariable analysis older age, time period of diagnosis, metastasis site, adjuvant chemotherapy, and primary tumor grade were independent predictors for short survival, whereas ER status was not. CONCLUSION: Nearly one out of six patients with MBC survive less than 3 months after diagnosis. Our findings demonstrate a different spectrum of MBC at population level and can potentially inform on individualized follow-up strategies and treatment algorithms.

Efficacy and safety of cyclin dependent kinases 4/6 inhibitors in the treatment of metastatic breast cancer: a real-world experience.

BACKGROUND: Randomized trials have shown survival gains for patients with metastatic breast cancer (BC) treated with CDK4/6 inhibitors (CDK4/6i) in combination with endocrine agents. It is not unlikely that there may be discrepancies between the generally fit clinical study population and the real-world setting that could affect adherence to treatment guidelines, tolerance to treatment and outcome. MATERIAL AND METHODS: Consecutive patients with metastatic or locally advanced and unresectable BC that were treated between July 2017 and January 2020 at Karolinska University Hospital, Stockholm, Sweden and that had received at least one dose of CDK4/6i were included in this retrospective study. The primary endpoint was safety, including toxicity according to CTCAE 5 and rates of treatment interruptions, dose reductions and discontinuations. The secondary endpoint was efficacy based on the treating physicians' assessments in terms of progression free (PFS) and overall survival (OS), as well as the factors associated with patient outcome. RESULTS: Eighty-eight patients were included in the analysis, with a median age of 67.2 years. Grade 4 neutropenia occurred in 9.1% of patients and one episode of neutropenic infection was observed. Dose reductions were made in 38.6% of patients, while 11.4% discontinued treatment due to toxicity, most commonly non-hematologic. After a median follow-up of 18.33 months, median PFS was 13.30 months (95% CI, 11.39-15.21) and median OS could yet not be estimated. In multivariable analysis, number of prior chemotherapy lines was an independent predictor for shorter PFS (HR = 3.28, 95% CI 1.50-7.16, p = .003). CONCLUSIONS: CDK4/6i administered in a real-world setting exhibits a similar toxicity profile but higher incidence of treatment discontinuation compared to randomized trials. Efficacy of CDK4/6i among patients pretreated with multiple therapy lines is markedly reduced.

Chemotherapy use near the end-of-life in patients with metastatic breast cancer.

INTRODUCTION: Very few data are available regarding the use of chemotherapy in patients with metastatic breast cancer (MBC) near the end-of-life, i.e., the final month. The aim of this study was to provide a descriptive analysis of its use in two different European geographic areas (Sweden and Greece). MATERIALS AND METHODS: We retrospectively collected data regarding clinicopathologic characteristics, survival, and use of chemotherapy during the final 30 days of life using two sources: for the Swedish cohort, patients who were diagnosed with MBC in 2010-2015 were identified from the Stockholm-Gotland population-based Breast Cancer Registry and treatment data were collected using hospital charts. For the Greek cohort, patients with MBC were identified from hospital charts at two hospitals in Athens and Crete. RESULTS: In the Swedish cohort, 1571 patients were identified; median overall survival was 16.96 months (95% CI 15.4-18.4). 23.2% of patients were treated with chemotherapy during the final month of life, with higher rates among patients ≤ 60 years (p < 0.001). Per OS monotherapy such as capecitabine or vinorelbine was most commonly used. In contrast, median OS in the Greek cohort (n = 966) was 49.8 months (95% CI 45.6-54.1) and 46.5% of patients received chemotherapy at the end-of-life, most commonly intravenous drug combinations. In multivariable analysis, age and albumin levels were statistically significantly associated with chemotherapy use in the Swedish cohort. CONCLUSION: Chemotherapy use near the end-of-life was common, which might negatively impact patient quality of life.

Wearing a bike helmet leads to less cognitive control, revealed by lower frontal midline theta power and risk indifference.

A recent study claims that participants wearing a bike helmet behave riskier in a computer-based risk task compared to control participants without a bike helmet. We hypothesized that wearing a bike helmet reduces cognitive control over risky behavior. To test our hypothesis, we recorded participants' EEG brain responses while they played a risk game developed in our laboratory. Previously, we found that, in this risk game, anxious participants showed greater levels of cognitive control as revealed by greater frontal midline theta power, which was associated with less risky decisions. Here, we predicted that cognitive control would be reduced in the helmet group, indicated by reduced frontal midline theta power, and that this group would prefer riskier options in the risk game. In line with our hypothesis, we found that participants in the helmet group showed significantly lower frontal midline theta power than participants in the control group, indicating less cognitive control. We did not replicate the finding of generally riskier behavior in the helmet group. Instead, we found that participants chose the riskier option in about half of trials, no matter how risky the other option was. Our results suggest that wearing a bike helmet reduces cognitive control, as revealed by reduced frontal midline theta power, leading to risk indifference when evaluating potential behaviors.

What you give is what you get: Payment of one randomly selected trial induces risk-aversion and decreases brain responses to monetary feedback.

In economic studies, it is standard practice to pay out the reward of only one randomly selected trial (pay-one) instead of the total reward accumulated across trials (pay-all), assuming that both methods are equivalent. We tested this assumption by recording electrophysiological activity to reward feedback from participants engaged in a decision-making task under both a pay-one and a pay-all condition. We show that participants are approximately 12% more risk averse in the pay-one condition than in the pay-all condition. Furthermore, we observed that the electrophysiological response to monetary rewards, the reward positivity, is significantly reduced in the pay-one condition relative to the pay-all condition. The difference of brain responses is associated with the difference in risky behavior across conditions. We concluded that the two payment methods lead to significantly different results and are therefore not equivalent.

Feedback negativity and decision-making behavior in the Balloon Analogue Risk Task (BART) in adolescents is modulated by peer presence.

Adolescent risk taking is strongly influenced by peer presence. The aim of the present study was to investigate the effect of peer presence on the ERP after negative and positive feedback in the time range of the feedback-related negativity (FRN). Eighteen male adolescents completed a version of the Balloon Analogue Risk Task (BART) under two conditions: playing alone and while observed by a peer. We recorded the ERPs after success or failure feedback and analyzed risk-taking behavior under both conditions. Behavioral results show that the participants were more cautious when being watched by a peer, especially after success. ERPs show that participants under peer presence exhibit more negative FRN after failure feedback than in the single condition, but no greater positivities after success feedback in the observed condition compared to the single condition. Results are in line with reinforcement learning theory and psychological aspects of loss prevention. The results suggest that the effect of peer presence on risk-taking behavior depends on the specific situational context.

A retrospective safety and efficacy analysis of the first patients treated with eribulin for metastatic breast cancer in Stockholm, Sweden.

BACKGROUNDS: Eribulin is a non-taxane, microtubule dynamics inhibitor approved for the treatment of patients with metastatic breast cancer (MBC) in Europe in March 2011. MATERIAL AND METHODS: For the purpose of an internal quality control, all patients with MBC treated with eribulin at Karolinska University Hospital were registered in a database. Clinical data were collected retrospectively for patients that were registered by August 2012 and safety and efficacy of eribulin were evaluated. Treatment toxicity including fatigue, neurotoxicity and infection was graded according to CTCAE v4.0. Objective response to treatment was investigated using routinely performed radiological assessments. When only clinical assessments were made, the evaluation of the treating physician was used. Furthermore, the efficacy of eribulin was investigated in different tumor subtypes. RESULTS: Forty-eight patients who received at least one cycle of eribulin were identified. Most patients were heavily pretreated with a median of 3 (range 1-7) previous chemotherapy lines prior to eribulin. Median patient age was 56 years (range 35-74). At the end of the analysis, 23 patients were alive and two were still treated with eribulin. No hypersensitivity reactions and no toxic deaths were seen. Fatigue grade 3-4 was observed in three patients (6.3%). One patient experienced grade 4 neurotoxicity. Grade 3-4 neutropenia was documented in 18.8%, and three patients were treated for a grade 3 infection. Interestingly, three individuals developed Herpes zoster reactivation. One patient responded to treatment with complete remission, while 33.3% had a partial response. 48% of all patients had a clinical benefit (objective response or stable disease for more than six months). CONCLUSIONS: Eribulin administered outside of a clinical trial in patients with advanced breast cancer was safe and well tolerated. A clinical benefit was seen in half of the cases. No statistically significant differences in objective response or survival were observed between histopathological subgroups.