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PurposeTo determine if women with breast cancer that undergo fertility preservation (FP), with or without hormonal stimulation, present with an increased risk of breast cancer recurrence.MethodsA matched cohort study on women with breast cancer attempting to ensure FP in Stockholm from 1999 to 2013 [exposed women (n = 188), age-matched unexposed controls (n = 378)] was designed using the Stockholm regional data from the Swedish National Breast Cancer Quality Register. Breast cancer relapse rates [incidence rate ratio (IRR)] and 95% confidence interval (CI) were estimated using Cox regression and adjusted for potential confounding factors. Completeness of the registry at the time of the study was close to 99%.ResultsMost women attempted FP by hormonal stimulation treatment (n = 148, 79%) with the objective of freezing their eggs or embryos. A smaller group elected FP methods without hormone stimulation (n = 40, 21%). Women who received hormone stimulation did not present with a higher relapse rate than unexposed control women in a model adjusted for age and calendar period of diagnosis (IRR 0.59, 95% CI 0.34–1.04). The results remained virtually unchanged after adjustment for tumor size, estrogen receptor status, affected lymph nodes, and chemotherapy treatment (IRR 0.66, 95% CI 0.37–1.17).ConclusionEvidence was not found that fertility preservation, with or without hormonal stimulation, was associated with an increased risk of breast cancer recurrence. The high coverage rate of this population-based study supports the safe practice of fertility preservation in young women with breast cancer.

Abstract Background No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies. Methods We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18–65 years were randomized 1:1 to receive ETVAX® or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence. Results The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX® recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of ≥2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX® recipients (93%) responded to either LTB or O78. Conclusions This Phase 2b trial is the largest on ETVAX® undertaken amongst travellers to date. ETVAX® showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.

Enterotoxigenic Escherichia coli (ETEC) causes 75 million diarrhoea episodes with up to 42 000 deaths annually in children. To prevent ETEC in children, we aimed to evaluate the safety, immunogenicity, and efficacy of ETVAX, an oral, inactivated, whole-cell ETEC vaccine with toxoid and double-mutant heat-labile toxin adjuvant. In this phase 2b, double-blind, placebo-controlled trial, Gambian children aged 6–18 months were recruited from four enrolment centres and block-randomised (1:1) via a computer-generated sequence, stratified by enrolment centres, to receive ETVAX or placebo on days 1, 15, and 90. Parents, staff, investigators assessing outcomes, and investigators analysing the data were masked to group assignment. An immunogenicity subset was assessed for serum antibody responses to ETEC colonisation factors and heat-labile toxin. The primary safety endpoint was serious adverse events, assessed in all children who received at least one intervention dose. The primary efficacy endpoint was vaccine efficacy against moderate-to-severe ETEC-positive diarrhoea (MSD-ETEC), excluding co-infections with Cryptosporidium spp, norovirus genogroup II, rotavirus, or Shigella spp, assessed in the per-protocol population. Secondary endpoints included vaccine efficacy against MSD-ETEC regardless of copathogens and against moderate-to-severe diarrhoea (MSD) regardless of cause. Exploratory vaccine efficacy analyses were against MSD-ETEC excluding only enteroparasitic copathogens (Giardia lamblia and Cryptosporidium) and against MSD-ETEC regardless of copathogens when first dose was given before age 9 months. This trial was registered with the Pan African Clinical Trials Registry (PACTR20201081921856). Between Feb 22, 2021, and June 24, 2022, 5253 children were screened and 4936 (2499 [51%] girls, 2437 [49%] boys) were randomly assigned (2468 to ETVAX, 2468 to placebo). Serious adverse events occurred in 24 (1·0%) of 2474 in the vaccine group and 32 (1·3%) of 2462 in the placebo group, with none related to the investigational product. Immunogenicity was assessed in 122 children. ETVAX increased antibodies to colonisation factors (CFA/I, CS3) and heat-labile toxins. Vaccine efficacy was 26·6% (95% CI −58·3 to 66·0; p=0·43) for the primary endpoint, 48·2% (p=0·053) against MSD-ETEC regardless of copathogens, and 80·6% (p=0·0092) when excluding enteroparasitic copathogens. Vaccine efficacy against all MSD-ETEC reached 67·8% (p=0·026) when dosing started before age 9 months. Vaccine efficacy against MSD regardless of cause was 21·4% (p=0·032). ETVAX was safe and immunogenic. Although the primary endpoint was not met, the secondary and exploratory findings suggest ETVAX protects Gambian children against ETEC-positive MSD particularly when administered before age 9 months and when children were not co-infected with enteroparasites. ETVAX also showed a reduction in all-cause MSD. These results support advancing ETVAX to a pivotal phase 3 trial. European & Developing Countries Clinical Trials Partnership.