Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails

Vom einfachen Komplex zum komplexen Gitter : Supramolekulare Komplexchemie

Koordinationsverbindungen, die bereits im vorletzten Jahrhundert durch die klassische Komplexchemie und Koordinationslehre beschrieben wurden und seit den späten 50iger Jahren intensiv auf dem Gebiet der homogenen und heterogenen Katalyse Einsatz finden, stehen erneut im Mittelpunkt eines neuen Forschungsbereichs: der metallo-supramolekularen Chemie. Komplizierte, supramolekulare Liganden, als Weiterentwicklung einfacher einzähniger Liganden und Chelatliganden, führen auf der Basis von Selbstorganisations- und Selbsterkennungsprozessen zusammen mit koordinierenden Metallionen zu genau definierten supramolekularen Architekturen. Die Natur nutzt diese als wesentliche Funktionsträger in biologischen Systemen, z. B. den Hämoglobin-Eisen-Komplex. Diesem Vorbild folgend versucht die supramolekulare Chemie, hochkomplexe, jedoch genau definierte Geometrien, wie Helikate, Fäden, Leitern, Rechen oder Gitter präparativ herzustellen und somit neuartige Materialien mit speziellen Eigenschaften zu entwickeln. Der Metallkomplex als zentrale Einheit der neuen Verbindungsklasse kann zu funktionalen supramolekularen Systemen führen. Diese könnten Anwendungen auf den Gebieten der Polyelektrolyte, der Elektrochemie (elektrisch leitende Polymere und Redoxkatalysatoren) und der Photochemie (organische Solarzellen) ermöglichen

Engineering with metallo-supramolecular polymers : linear coordination polymers and networks

Here we demonstrate the synthesis of telechelics with different spacer units and different numbers of metal-complexing units, like -methoxy--(2,2:6,2-terpyrid-4-yl)-poly(ethylenoxide)78 (1), bis(2,2:6,2-terpyrid-4-yl) di(ethylene glycol) (2), bis(2,2:6,2-terpyrid-4-yl)-poly(ethylene oxide)180 (3) and tris[(2,2:6,2-terpyrid-4-yl)-oligo (ethylenoxy-)3.33]glycerin (4) utilizing 4-chloro-2,2:6,2-terpyridine. The complexation behaviour of a variety of metal-salts towards the telechelics was studied and different supramolecular architectures were investigated, such as symmetric polymeric complexes and linear coordination polymers. Furthermore, attempts have been undertaken to prepare metallo-supramolecular cross-linked systems

Engineering with metallo-supramolecular polymers : linear coordination polymers and networks

Here we demonstrate the synthesis of telechelics with different spacer units and different numbers of metal-complexing units, like -methoxy--(2,2:6,2-terpyrid-4-yl)-poly(ethylenoxide)78 (1), bis(2,2:6,2-terpyrid-4-yl) di(ethylene glycol) (2), bis(2,2:6,2-terpyrid-4-yl)-poly(ethylene oxide)180 (3) and tris[(2,2:6,2-terpyrid-4-yl)-oligo (ethylenoxy-)3.33]glycerin (4) utilizing 4-chloro-2,2:6,2-terpyridine. The complexation behaviour of a variety of metal-salts towards the telechelics was studied and different supramolecular architectures were investigated, such as symmetric polymeric complexes and linear coordination polymers. Furthermore, attempts have been undertaken to prepare metallo-supramolecular cross-linked systems

From small organic entities to metallo-supramolecular polymers

Abstract onl

Access to supramolecular polymers: large scale synthesis of 4'-chloro-2,2':6',2''-terpyridine and an application to poly(propylene oxide) telechelics

A new improved large scale synthesis of 4-chloro-2,2 : 6,2-terpyridine is described in detail. Williamson type ether reactions were utilized for a high yield reaction of 4-chloro-2,2 : 6,2-terpyridine with ,-bishydroxy-functionalized poly(propylene oxide). The completeness of the functionalization was proven by NMR, GPC and MALDI-TOF-MS investigations. The application of ruthenium(III)/(II) chemistry allowed then the construction of ABA type non-covalent architectures