Gunilla Hallberg

Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

Post‐traumatic stress symptoms in Swedish obstetricians and midwives after severe obstetric events: a cross‐sectional retrospective survey

To examine post‐traumatic stress reactions among obstetricians and midwives, experiences of support and professional consequences after severe events in the labour ward.

The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle

BackgroundIn order to unravel the interactions between the epithelium and the extra cellular matrix (ECM) in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle.MethodsTissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38) and Real-Time RT-PCR (n = 20). Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years) with regular menstrual cycles (28 +/- 7 days). None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses.ResultsBy real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02) and syndecan-1 (p = 0.03) and syndecan-4 (p = 0.02) was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase.ConclusionsOur study shows, for the first time in the healthy breast, a significantly lower expression of the genes for the three proteoglycans, decorin, syndecan-1 and syndecan-4 in the luteal phase during the menstrual cycle. These changes were registered under normal physiologic conditions. Since ECM molecules appear to be involved in tumor progression, these findings in the normal breast could constitute a base for further studies in women receiving hormonal therapy or those with breast cancer.

Umbilical cord blood sampling — a tool for delivery quality control?

Background. Regular cord blood analysis post partum is regarded by many as one of the most accurate and objective methods of auditing intrapartum care. Emergency cesarean sections and ventouse deliveries, due to the threat of asphyxia, are examples where post partum acid base data from the umbilical artery ought to be a must. The possibility of having cord blood analyses as a routine at all deliveries was investigated in this study.

Effects of pre- and postmenopausal use of exogenous hormones on receptor content in normal human breast tissue: a randomized study.

Objective. To examine the effects of exposure to endogenous and exogenous hormones on estrogen receptor-α (ERα) and progesterone receptor (PR) levels in normal human breast tissue. Methods. In a randomized study of women scheduled for mammary reduction plasty (n = 81), ERα and PR content in breast parenchyma was analyzed in premenopausal (n = 49) and postmenopausal (n = 16) women. Premenopausal women were randomized to surgery in the follicular or luteal phase of the menstrual cycle or after oral contraceptive treatment for 2 months. Postmenopausal women were randomized to sequential or estrogen-only therapy for 2 months prior to surgery. Results. ERα content was higher in parous than in nulliparous (p = 0.009) premenopausal women and displayed a positive association with age (rs = 0.51, p = 0.0002). Compared with premenopausal women in the follicular phase, postmenopausal women had higher ERα content (p = 0.040) whereas premenopausal women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) content. Smokers had lower PR content than non-smokers (p = 0.02). Conclusion. In the present study ERα content was higher in parous than in non-parous women and associated with premenopausal age. Short-term oral contraceptives yielded lower ERα and PR contents. Postmenopausal estrogen/progestogen combined therapy yielded lower PR content than estrogen-only therapy.

Self-reported exposure to severe events on the labour ward among Swedish midwives and obstetricians: A cross-sectional retrospective study

BACKGROUND The process of delivery entails potentially traumatic events in which the mother or child becomes injured or dies. Midwives and obstetricians are sometimes responsible for these events and can be negatively affected by them as well as by the resulting investigation or complaints procedure (clinical negligence). OBJECTIVE To assess the self-reported exposure rate of severe events among midwives and obstetricians on the delivery ward and the cumulative risk by professional years and subsequent investigations and complaints. DESIGN Cross-sectional survey. PARTICIPANTS Members of the Swedish Association of Midwives (SFB) and the Swedish Society of Obstetrics and Gynaecology (SFOG). METHODS A questionnaire covering demographic characteristics, experiences of self-reported severe events on the delivery ward, and complaints of medical negligence was developed. Potential consequences of the complaint was not reported. A severe event was defined as: 1) the death of an infant due to delivery-related causes during childbirth or while on the neonatal ward; 2) an infant being severely asphyxiated or injured at delivery; 3) maternal death; 4) very severe or life threatening maternal morbidity; or 5) other stressful events during delivery, such as exposure to violence or aggression. RESULTS The response rate was 39.9% (n=1459) for midwives and 47.1% (n=706) for obstetricians. Eighty-four percent of the obstetricians and almost 71% of responding midwives had experienced one or more self-reported severe obstetric event with detrimental consequences for the woman or the new-born. Fourteen percent of the midwives and 22.4% of the obstetricians had faced complaints of medical negligence from the patient or the family of the patient. CONCLUSIONS A considerable proportion of midwives and obstetricians will, in the course of their working life, experience severe obstetric events in which the mother or the new-born is injured or dies. Preparedness for such exposure should be part of the training, as should managerial and peer support for those in need. This could prevent serious consequences for the health care professionals involved and their subsequent careers.

Higher alcohol consumption in early pregnancy or low-to-moderate drinking during pregnancy may affect children's behaviour and development at one year and six months

It is unclear whether low‐to‐moderate alcohol consumption during pregnancy affects child development. This study examined the effects that a mothers self‐reported alcohol consumption had on her pregnancy and her childs birth, behaviour and development.