Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

PURPOSE In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODS We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. RESULTS In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

Gerd Schwerhoff and Alex Kästner, eds., Göttlicher Zorn und menschliches Maß: Religiöse Abweichung in frühneuzeitlichen Stadtgemeinschaften (Constance: UVK, 2013)

This book presents six essays by researchers associated with the Technological University of Dresden’s collaborative research centre, Transzendenz und Gemeinsinn, on the interesting theme of religious deviance in early modern cities. As Gerd Schwerhoff and Alexander Kästner make clear in the introduction, early modern religious deviance is a broad concept, and one difficult to delimit, particularly because most early modern secular crimes—theft, adultery, witchcraft and magic, blasphemy—were also sins. Should such offences fall under the rubric of secular or religious deviance? Historians have traditionally approached these offences as secular (and indeed, they were commonly prosecuted in ‘secular’ courts), but one cannot help but see their religious roots. Moreover, religious deviance also encompassed divergence over confessional practices and doctrinal beliefs among Catholics, Protestants, Anabaptists, Calvinists, and so on. To try and demarcate this broad field, Schwerhoff and Kästner advocate using the ‘labelling approach’, drawn from sociology and previously used in Schwerhoff’s work: that is, behaviour only becomes deviant when contemporaries classified (or labelled) it as such (p. 27).