Correction: Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

[This corrects the article DOI: 10.1055/a-2238-3153.].

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy. Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed. Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients). Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.

Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress during pregnancy: Effects on gestational age and infant's anthropometric measures at birth.

BACKGROUND: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. METHODS: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 ±â€¯1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth. RESULTS: Maternal prenatal distress during late gestation was associated with significant reduction in birth weight (-217 g; p = .005), birth length (-1.2 cm; p = .005) and head circumference (-0.8 cm; p = .001). Prenatal stress was modestly but significantly associated with altered diurnal cortisol pattern (flattened cortisol decline and higher evening cortisol), which in turn was significantly related to reduced length of gestation. No evidence for a profound interaction between maternal cortisol level in late pregnancy and infant's anthropometric measures at birth (i.e., birth weight, length, head circumference) was found. CONCLUSION: Prenatal stress is associated with flattened circadian saliva cortisol profiles and reduced infant's anthropometric measures at birth. HPA system activity during pregnancy may be related to low gestational age. The effect of prenatal stress might be partly mediated by maternal-placental-fetal neuroendocrine mechanisms especially the dysregulation of diurnal cortisol profile.

Serum folate and Vitamin B12 levels in women using modern oral contraceptives (OC) containing 20 microg ethinyl estradiol.

OBJECTIVE: The effects of modern oral contraceptives (OC) on serum concentrations of folate and cobalamin are controversial. STUDY DESIGN: Case-control study on the cobalamin and folate status of 71 healthy female nulligravidae using "low dose" OC for >or=3 months and 170 controls. Factors interfering with vitamin metabolism were thoroughly controlled. Serum concentrations were measured by commercial assays. The results were evaluated using Mann-Whitney's U-test and chi(2) analysis. RESULTS: OC-users showed significantly lower concentrations of cobalamin than controls. The rates of women with reduced, normal, and elevated levels differed significantly. Nine users but no control had frank cobalamin deficiency without clinical symptoms. Folate levels did not differ between the groups. Vegetarian diet, smoking or obesity did not have a significant influence. CONCLUSIONS: Routine measurement of cobalamin or folate in women using "low dose" OC is not warranted. Vitamin supplementation or different contraceptive methods should be considered in women with pre-existing cobalamin deficiency or restrictive dietary habits.