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

LASERSPECTROSCOPIC INVESTIGATION OF THE VAN DER WAALS MOLECULE NaKr

$^{1}$ Parts of these results have been submitted for publication: E.Zanger, V.Schmatioch, D.Zimmermann, accepted by J.Chem.Phys., to appear in April 88Author Institution: Institut f\""{u}r Strahlungs- und KernphysikThe absorption spectrum of NaKr due to the transition $X \Sigma \rightarrow A$ has been investigated in the wavelength region between 16790 and $16950 cm^{-1}$ with high resolution by means of laserspectroscopy using a tunable cw dye laser and producing the molecules by supersonic expansion of a mixture of sodium vapor and krypton gas into a vacuum. In order to get an assignment of rotational quantum numbers to the numerous molecular absorption lines, despite of strong overlapping of vibrational bands and despite of the presence of several Krisotopes, the method of optical-optical double resonance has been applied. In addition, the spectral intensity distribution of the fluorescence light has been investigated, thus allowing an assignment of vibrational quantum numbers. Up to now, the molecular parameters B, D, H of rotation. $A, A_{n}, A_{n}$ of fine structure splitting and p. $p_{n}$ of $\Lambda$-type doubling have been determined with high precision for the vibrational states $8 \leq v^{\prime} \leq 14$ of the $\Pi$ $\Pi$-state and $0 \leq v^{\prime \prime} \leq 2$ for the $X \Sigma$ -state together with the wavenumbers of the band origins ***. The values of the fine structure splitting constants A. decreasing from A = 939 GHz for $v^{\prime} = 8$ to A = 661 GHz for $v^{\prime} = 13$, are unexpectedly high in comparison with the 3P-fine structure splitting of the sodium atom of 517 GHz. The $\lambda$-doubling parameter p decreases with increasing v' and changes sign near $v^{\prime} = 13$. The interatomic potential of the $A \Pi-$ and of the $X \Sigma$-state have been deduced from our data and will be compared to the results of recent model potential calculations

Separation of volatile and non-volatile aerosol fractions by thermodesorption: instrumental development and applications

An instrument to remove volatile material from aerosol particles by thermal desorption is presented. The thermodesorber consists of a heated tube, where volatile material is desorbed from the particles, and a water or air-cooled tube, consisting of activated charcoal. This last tube removes desorbed material and thus prevents it from re-adsorbing onto particles. Although designed for measuring particulate emissions from combustion processes it can also be applied to atmospheric aerosols. After theoretical and experimental determination of thermodesorber operating characteristics (temperature profile, losses, removal of desorbed material), examples of applications in several fields are given. Examples of atmospheric measurements at several remote and urban sites are presented. In combustion technology, the thermodesorber is applied to remove all volatile materials, allowing separation of volatile species and the non-volatile core (mainly elemental carbon) of combustion particles. Finally, the thermodesorber is used to study adsorption and desorption processes of polycyclic aromatic hydrocarbons on particles

Ability of nitrones of various structures to control the radical polymerization of styrene mediated by in situ formed nitroxides

The ability of several nitrones to control the radical polymerization of styrene at 110 °C has been investigated by high-throughput experimentation. The nitrone/free radical initiator pair dictates the structure of the nitroxide and the alkoxyamine formed in situ, which determines the position of the equilibrium between the active and the dormant species operating in the nitroxide-mediated polymerization. For the styrene polymerization to be controlled, the nitrone must be reacted with 2,2'-azo-bis-isobutyronitrile (AIBN) at 85 °C, prior to addition of styrene and polymerization at 110 °C. The effect of the nitrone structure on the kinetics of the styrene polymerization has been emphasized. Amongst all the nitrones tested, those of the C-phenyl-N-tert-butylnitrone (PBN) type are the most efficient in terms of polymerization rate, control of molecular weight and polydispersity. Electrophilic substitution of the phenyl group of PBN by either an electrodonor or an electroacceptor group has only a minor effect on the polymerization kinetics. Importantly, the polymerization rate is not governed by the thermal polymerization of styrene but by the alkoxyamine formed in situ during the pre-reaction step. The initiation efficiency is, however, very low, consistent with a limited conversion of the nitrone into nitroxide and alkoxyamine