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thrombophilia, antenatal and postpartum prophylaxis should be used. Prophylactic treatment with LMWH or UFH can be stopped at 12 to 24 hours before induction or elective CS; full anticoagulation should be withheld for 24 hours.For asymptomatic women with no prior VTE or APO but with thrombophilia, there is not enough evidence to recommend anticoagulant drug treatment during pregnancy, unless there are other risk factors. Those with AT-III deficiency, or who are homozygotes, or compound heterozygotes for factor V Leiden and prothrombin G20210A mutations require therapeutic UFH or LMWH throughout pregnancy. Fitted compression stockings, calcium, and vitamin D supplementation may be of benefit. Women with no history of thrombophilia or VTE but with other risk factors can be treated with intermittent compression devices and/or UFH or LMWH prophylaxis. Women who are AT-III deficient may require AT-III concentrate in addition to anticoagulation.Management of infants in at-risk pregnancies includes avoidance of maternal anticoagulation with warfarin before delivery, screening of infants with known thrombophilic conditions, examination of the placenta and umbilical cord by a pathologist (for counseling in future pregnancies), and evaluation and prompt treatment, as necessary, for additional risk factors (eg, asphyxia, polycythemia, dehydration, septicemia, and cardiac diseases).Specific recommendations for anesthesia for women with VTE include general anesthesia for CS if delivery is within 12 hours of taking a prophylactic dose of LMWH. Epidural and spinal anesthesia should be delayed for 10 to 12 hours after the last dose of prophylactic LMWH and for 24 hours with full anticoagulation. Patients on LMWH should receive the next dose 10 to 12 hours after removal of the catheter. Epidural anesthesia should be avoided during peak heparin concentrations to reduce the risk of epidural hematoma.In summary, thrombophilia and the development of VTE during pregnancy can have serious repercussions for mother and fetus. Antithrombotic treatments all have limitations in pregnant women and management of thromboprophylaxis during pregnancy requires extensive interaction between patients and clinicians. Treatment plans have to be individualized and require frequent modification over the course of pregnancy, labor, delivery, and postpartum. Due to a lack of evidence-based guidelines, the authors recommended large, prospective, randomized studies of women with risks for VTE.

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SUMMARY The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross‐sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.

Recent data demonstrating a correlation between lymph node positivity at the time of detection, and the probability of disease recurrence even decades post detection only solidifies the principle that the detection of breast cancer prior to lymph node metastasis can appreciably better clinical outcomes. Although radiologic methods have greatly improved early detection and remain the mainstay for detection, molecular assays to complement existing strategies will reduce number of false positives as well as enhance detection in cases that preclude conclusive diagnosis with radiologic techniques. Normal breast biology is routinely studied using tissues from reduction mammoplasty or normal tissues adjacent to tumor (NATs). However, studies have shown histologic abnormalities in reduction mammoplasty samples and DNA methylation and gene expression abnormalities in NATs due to “field” effects of the tumor. To interrogate the differences between normal breast and NATs as potential early detection markers, we created a tissue microarray (TMA) comprising breast tissues of 100 age-matched healthy women from the Komen Tissue Bank (KTB) and tumor-NAT pairs from 100 women (a total of 300 samples). Approximately 50% of women in each set were of African American (AA) ancestry and the remaining was of European decent. The TMAs was curated as such, because of our recent findings on ethnicity-dependent differences in breast stem-luminal progenitor-mature cell hierarchy. TMA was analyzed for ZEB1, an oncogenic transcription factor that is central to cell fate and stemness, and estrogen receptor alpha (ERα) and FOXA1, which are expressed predominantly in hormone-responsive mature luminal cells. ZEB1 expressing cells were localized to surrounding ductal structures of the normal breast, whereas ERα+ and FOXA1+ cells were located within the ductal compartment. KTB-normal of AA women contained significantly higher levels of ZEB1+ cells compared to KTB-normal of Caucasian women (CA). We observed only marginal increases in ZEB1+ cells in NATs or tumors of AA women. By contrast, in CA women, both NATs and tumors compared to KTB-normal contained higher levels of ZEB1+ cells. The unique localization pattern external to the ductal structures, as well as intrinsically higher expression in AA women suggest that ZEB1+ cells serve not only as stem cells from which cancers may originate but could also contribute to the microenvironment conducive for ductal tumor progression leading to aggressive and early onset of breast cancer as observed in AA women. Conversely, KTB-normal of AA showed modestly higher FOXA1 expression compared to CA women, and further, FOXA1 levels were declined in NATs of AA but not CA women. ERα levels did not change in any of our analyses, pointing to the specificity of ethnicity-dependent changes in this TMA. We also noted ethnicity-dependent variations in the levels of CD8+ T cells, PD-1+ immune cells and PD-L1+ cells but not CD68+ macrophages in NATs, suggesting distinctive immune environment in NATs. This comprehensive approach will not only serve as a platform to develop tumor-adjacent “normal” tissues as molecular markers for early detection but also provides a molecular basis for aggressive breast tumor in AA women. Citation Format: Nakshatri H, Kumar B, Burney H, Cox ML, Jacobson M, Sandusky G, D'Souza-Schorey C, Storniolo AM. Harnessing the distinctive properties of tumor-adjacent tissues to develop ethnicity-dependent biomarkers of breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-11.