Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.
We analysed clinical ...data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.
Median age at diagnosis of BMs was 56 years (22–90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)–positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000–2009 with 2010–2015 (51%–44%), whereas the percentage of patients with luminal-like tumours increased (28%–34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval CI: 6.7–8.0 months). One-year survival rate was 37.7% (95% CI: 35.2–40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0–13.4) compared with 5.9 months (95% CI: 5.0–7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9–5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).
Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
•The first analysis of 1712 patients of breast cancer patients with brain metastases (BMs) is presented.•Localisation of BMs was different depending on tumour subtypes.•Survival times differ depending on the subtype and localisation of BMs.•A change in the incidence of BMs over time was observed.
An unusually low density solar wind event was observed in December 2022 moving past both Earth and Mars. The source was traced back to a coronal hole and active region on the Sun's surface. The ...resulting solar wind lead to the development of a co-rotating interaction region (CIR) and trailing rarefaction region that lasted for multiple solar rotations. Within this structure, the solar wind conditions, including density, velocity, and magnetic field magnitude and orientation drastically changed. In this study we analyze the response of the Martian ionosphere using MAVEN data to these changing solar wind conditions. The low density solar wind region associated with the December event resulted in the expansion of the Martian ionospheric boundaries. We show that the ion composition boundary (ICB) is located at extreme altitudes that are beyond previously observed locations from the MAVEN mission between 2015 and 2018. Furthermore, the boundary between shocked solar wind and the Martian ionosphere identified using electron and ion data moved together on the dayside of the planet with the changing solar wind conditions. However, at the flank region these boundaries do not move together, and we show here that the decoupling of the two boundaries may be the result of a change in the interplanetary magnetic field azimuthal angle.
Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with ...long-term survival is important for improving treatment modalities.
A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors.
Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months interquartile range (IQR) 30.3 overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients.
In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment.
•Median OS in long-term survivors was about two times higher than the cut-off of 15 months (IQR 30.3 months).•Median OS according to subtypes were 33.9 in HER2-positive, 26.9 in luminal-like and 26.5 months in TNBC patients•Long-term prognostic factors were age, ECOG, number of BM, pos. HR/HER2 status, no ECM and syst. treatment after BM.
Abyssal spinel peridotites from Hess Deep, East Pacific Rise (ODP Leg 147) were investigated concerning their major, minor, and trace element mineral chemistry and the incorporation of structural ...water in orthopyroxene.
The rocks are partially serpentinized harzburgites containing primary minerals of olivine, orthopyroxene, clinopyroxene, and spinel. Orthopyroxene is enstatitic with Mg# (Mg/(Mg+Fe)) between 0.90 and 0.92 and Al2O3 from 0.5 to 2.9wt.%. The residual harzburgite experienced high degrees of melt removal in the spinel peridotite stability field. The average degree of partial melting was calculated to be 17.5% (range: 16.4–17.8%). Trace element data of ortho- and clinopyroxenes reflect this strong depletion, characteristic for the restitic nature of abyssal peridotites. Mantle re-equilibration temperatures around 1000°C indicate that, after melt extraction and before exhumation to the ocean floor, the rocks experienced significant cooling in the spinel peridotite facies. Water contents of orthopyroxene range from 86 to 233wt. ppm H2O with an average concentration of 142wt. ppm H2O. These results represent the first data on water contents in the sub-pacific mantle obtained by direct measurements of sub-oceanic peridotite. The water contents are not related to mineral chemistry, stratigraphy, melting degree, mantle equilibrium conditions or oxidation state. Calculated post-melt peridotite water contents vary between 40 and 100wt. ppm H2O.
Compared to Mid-Atlantic Ridge peridotites, the East Pacific Rise samples of Leg 147 contain somewhat lower water concentrations than samples from Leg 153 and considerably higher contents than those of Leg 209 (Gose et al., 2009; Schmädicke et al., 2011). In Leg 147, the strongest OH absorbtion band occurs at 3420cm−1, wheras orthopyroxene from MAR peridotite (Legs 153 and 209) has its strongest absorbtion band at 3566 and 3522cm−1. The mantle equilibrium temperature of Leg 147 peridotites is lower than that of Leg 209 (~1250°C) but close to that of Leg 153 samples (950–1000°C). The high degree of partial melting of Leg 147 peridotite samples overlaps with the Leg 209 samples. In accordance to this data we conclude that in order to obtain relatively high water contents of up to 233wt. ppm in depleted peridotite, after melt removal water must have re-entered the orthopyroxene structure. We suggest that re-equilibration of water contents took place under spinel-facies conditions before exhumation of the tectonite, since elevated temperatures enhance diffusion and elevated pressures facilitate hydrogen uptake. The extended time span between melt removal and uplift inferred from significant isobaric cooling of at least 200K at spinel-facies depth facilitates re-equilibration of water contents and may explain the high concentrations. Exhumation from spinel-facies depth was fast and accompanied by further cooling such that re-equilibration to lower pressure assemblages and decompression-induced water loss were prevented.
•Water contents of orthopyroxene from EPR spinel peridotites range from 86 to 233wt. ppm H2O.•First data for sub-pacific mantle obtained by direct measurements of peridotite.•Water contents not related to mineral chemistry, melting degree, or P-T conditions.•Re-equilibration temperatures are around 1000°C.•Between melt extraction and exhumation rocks cooled in spinel peridotite facies.
Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with ...HER2-positive breast cancer and BMs is vital.
A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.
Patients with HER2-positive breast cancer and BMs were—when compared with HER2-negative patients—slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis ≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001, lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.
We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.
•Patients with HER2-positive BMs from breast cancer have the best prognosis compared with other tumor subtypes.•Among HER2-positive patients, hormone receptor-positive patients have the longest survival.•HER2-targeted therapy is significantly associated with a better prognosis in patients with BMs.•On average, two HER2-targeted therapy lines were administered prior to the development of BMs.•New compounds are urgently needed to improve the outcome of this subgroup of patients.
Background/Aims: Many studies have shown that not only pharmacological treatment but also cognitive stimulation in the early stages of Alzheimer's disease (AD) improves language processing and ...(other) cognitive functions, stabilizes Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) functions and increases the subjective quality of life (wherein a combination of pharmacological intervention and cognitive stimulation could provide greater relief of clinical symptoms than either intervention given alone). Today, it is no longer the question of whether cognitive stimulation helps but rather what kind of stimulation helps more than others. Methods: A sample of 42 subjects with mild AD (all medicated with an acetylcholinesterase inhibitor and well adjusted) underwent clinical and cognitive evaluation and participated in a 6-month study with 2 experimental groups (i.e. ‘client-centered' global stimulation vs. cognitive training) and a control group. Since the test performance also depends on the individual test, we used a wide variety of tests; we z-transformed the results and then calculated the mean value for the global cognitive status (using the Mini-Mental State Examination) as well as for the single functional areas. Results: Between-group differences were found, they were overall in favor of the experimental groups. Different functional areas led to different treatment and test patterns. Client-centered, global, cognitive therapy stimulated many cognitive functions and thus led to a better performance in language processing and ADL/IADL. The subjective quality of life increased as well. The cognitive training (of working memory) improved only the ADL/IADL performance (more, however, than client-centered, global, cognitive stimulation) and stabilized the level of performance in the other three functional areas.
PDF
