No abstract

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.

Purpose To examine common themes and synthesize data surrounding pregnancy and parenthood during surgical residency training. Method The authors conducted a systematic search of the literature in March 2019. They searched MEDLINE, EMBASE, and Scopus, seeking articles published from 2003 to 2018 that focused on pregnancy, parenthood, and the experience of surgical residents. They excluded articles that examined nonsurgical programs, as well as editorials, abstracts, and commentaries. Two investigators independently reviewed all citations, selected articles for full-text review, and extracted data from the selected articles. Results Of 523 titles and abstracts screened, 27 were included. Overall, female surgical residents had fewer children during residency training than their male counterparts (18%–28% vs 32%–54%). As compared with the general population, surgical residents had their first child later in life (30–34 vs 25 years old), and had fewer children overall (0.6–2.1 vs 2.7). Infertility rates were higher among female surgeons than in the general population (30%–32% vs 11%), as were assisted reproductive technology rates (8%–13% vs 1.7%). Pregnant surgical residents experienced a high rate of obstetrical complications; working more than 6 overnight calls shifts per month or 60 hours per week were predictors of increased complication rates. The authors noted no differences in attrition, caseload, or exam pass rates amongst female surgical residents who had become pregnant as compared with other residents. Despite these similar academic outcomes, negative attitudes and perceptions toward pregnancy during residency were consistently identified. Conclusions Female surgical residents experience high rates of infertility and obstetrical complications, contend with negative attitudes and stigma during their pregnancies, and voluntarily delay childbearing. Formal maternity policies, a shift in surgical culture, and ongoing discussion with all stakeholders are needed to attract and retain female surgical residents.