Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammationassociated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor α (ERα, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-β (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk. Cancer Prev Res; 3(3); 301-11. ©2010 AACR.

Breast cancer risk increases transiently in the period following pregnancy; pregnancy-associated breast cancers (PABC) are more aggressive than cases diagnosed in nulliparous women. We have previously reported that in the normal human breast pregnancy results in the upregulation of a number of inflammation related genes, suggesting a pro-tumorigenic environment as well as downregulation of ESR1 (ERα) and ERBB2 (HER2) and upregulation of ESR2 (ERβ), suggesting a protective effect. In this study, we aimed to investigate the possibility of differential regulation of the same gene set modulated in the normal breast, in human breast tumors following pregnancy. Gene expression was measured by real-time PCR on tumor regions isolated by laser capture microdissection from paraffin sections. Immunohistochemistry was performed on tissue microarrays (TMA) for protein expression. Hierarchical clustering was performed using the average linkage method to determine coordinate expression of sets of genes. We find that breast cancers detected within 10 years following pregnancy display a different gene expression pattern than those detected in nulliparous breast cancer patients. The gene expression difference is mainly attributable to a triple negative (TNBC) subgroup found to be more frequent in PABCs up to 10 years following a pregnancy. We also show that protein and mRNA expression levels correlate in half of the proteins tested by TMA. Despite the fact that this is a small study of 53 patients, we identified a gene expression signature that is differentially expressed in pregnancy-associated TNBC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1512-7) contains supplementary material, which is available to authorized users.

The levels of inhibin A, PlGF, and endoglin in the second trimester can be combined using a predictive model to provide individualized risk estimates for early onset preeclampsia.

Background:Sports medicine is one of the most competitive fellowships in orthopaedic surgery. Despite its popularity, fellowship applicants have limited understanding of the orthopaedic sports medicine fellowship match process.Purpose:To define key outcomes in the orthopaedic sports medicine fellowship match, including the overall match rate, number of programs filled, and number of applicants ranked by programs that filled between 2010 and 2017.Study Design:Cross-sectional study.Methods:This study utilized data regarding the orthopaedic sports medicine fellowship match collected by the American Orthopaedic Society for Sports Medicine (AOSSM) from 2010 through 2017. Applicant data included number of applicants, number of matched and unmatched applicants, and percentage of applicants matching into their top choices. Fellowship program data included number of programs participating in the match and number of applicants ranked by filled and unfilled programs.Results:Between 2010 and 2017, the mean number of orthopaedic sports medicine fellowship applicants was 244.8. On average, 92.0% of applicants matched into a fellowship program. The mean number of programs participating in the fellowship match was 92.9, with a mean of 219.9 accredited positions and 5.4 nonaccredited positions. Over the time period studied, a mean of 75.8% of programs matched all available positions. Programs that matched fully ranked 9.0 applicants per position, on average, compared with a mean of 6.5 applicants ranked per position among programs that did not fully match (P = .0016).Conclusion:From 2010 to 2017, the number of applicants, positions available, overall match rate, and number of programs participating in the orthopaedic sports medicine fellowship match have remained consistent. The mean number of applicants per position ranked by fully matched fellowship programs was 9.0 compared with a mean of 6.5 applicants per position ranked by programs that did not fully match. These data may be helpful as we look to the future of orthopaedic sports medicine fellowship positions and the match process. In addition, this study reveals characteristics that divide sports medicine fellowship programs that fully match from those that do not. Applicants and/or fellowship program directors may utilize this information to modify their approach to the match process going forward.