Breast cancer risks in individuals testing negative for a known family mutation in BRCA1 or BRCA2

Genetic testing for BRCA1 and BRCA2 mutations in family members of individuals with known deleterious mutations can distinguish between patients at high risk of disease and those who are not. Some studies have suggested that individuals testing negative for known familial mutations (true negatives), may still have a higher risk of breast cancer (BC) than the general population. We have examined a prospectively followed cohort of true negative women in the US. Subjects were close relatives of known BRCA1 and BRCA2 mutation carriers who had undergone genetic testing, were negative for the known familial mutation, and were unaffected at the time of genetic testing. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated using SEER incidence rates. Among 375 true negatives, two invasive and two in situ BC and no ovarian cancers were diagnosed with mean follow up of 4.9 years (total of 1,962 person-years). Four invasive BC were expected, whereas two were observed, for an age-adjusted SIR of 0.52 (95% CI 0.13–2.09). We observed more cases of in situ BC (n = 2) than were expected (n = 0.9; SIR = 2.30; 95% CI 0.57–9.19). There were no cases of ovarian cancer observed; 0.4 case was expected. In this prospective study of women who were unaffected at the time of genetic testing and who were negative for the known familial mutation in BRCA1/2, no excess risk of invasive BC was observed. Our data suggest that such women in the US should adhere to population-based guidelines for breast cancer screening.     

Assessing the Accuracy of Pregnant Women in Recalling Pre-Pregnancy Weight and Gestational Weight Gain

ObjectiveMaternity care providers can use pre-pregnancy weight (PPW) and gestational weight gain (GWG) as markers for difficult delivery, and frequently obtain this information directly from the patient. The goal of this study was to determine whether women report their PPW and GWG correctly at the end of pregnancy.MethodsWe performed a prospective cohort study of 189 women delivering between June 1,2011, and July 31,2011, at the Saint John Regional Hospital or the Moncton Hospital in New Brunswick. Self- reported PPW and GWG were compared with measured weights obtained from the antenatal chart and upon presentation for delivery. Patient characteristics, BMI classification, and accuracy and degree of error in recall were assessed.ResultsThe majority of respondents were under 30 years of age (63.4%) and were delivering at term (96.3%). Ninety women (47.6%) were having their first baby. A record of weight measured in the first trimester was available for 98 respondents (51.9%); using this information, 44 women (44.9%) were determined to be overweight or obese at delivery. Approximately one third of women with a normal BMI were not able to recall their PPW or GWG accurately (± 1 kg). Among all BMI classes, there was a consistent pattern of under-reporting of PPW (by a mean of 1.52 kg) and over-reporting of GWG (by a mean of 1.61 kg), but several extreme outliers were identified.ConclusionAt the time of delivery, under-reporting of PPW and over-reporting of GWG are common and difficult to predict. Maternity care providers should be aware of this discrepant reporting of PPW and GWG and recognize the implications for intrapartum management and postpartum weight loss.     

The Impact of Increasing Obesity Class on Obstetrical Outcomes

ObjectiveNationally, rates of obesity continue to rise, resulting in increased health concerns for women of reproductive age Identifying the impact of maternal obesity on obstetrical outcomes is important to enhance patient care.MethodsWe conducted a retrospective cohort study of 6674 women who delivered a singleton infant at ≥ 20 weeks’ gestation between December 1, 2007, and March 31, 2010, at The Ottawa Hospital. Maternal pre-pregnancy BMI was used to classify women into normal, overweight, and obese (class I/II/III) categories according to WHO classifications. Obstetrical outcomes among obese women were compared with those of women with normal BMI Multivariable regression models were used to determine adjusted odds ratios and 95% confidence intervals.ResultsCompared with women with normal BMI, obese women had significantly higher rates of preeclampsia, gestational hypertension, and gestational diabetes, and these rates increased with increasing BMI (trend-test P < 0.001). There was a significant increase in rates of induction of labour in the obesity categories, from 25 3% in women with normal BMI to 42 9% in women with class III morbid obesity (aOR 1.67; 95% CI 1.43 to 1.93). Rates of primary Caesarean section rose with increasing BMI and were highest in women with class III morbid obesity (36 2% vs 22 1% in women with normal BMI) (aOR 1.46; 95% CI 1. 23 to 1.73).ConclusionIncreasing BMI is associated with increasing rates of preeclampsia, gestational hypertension, and gestational diabetes There is a significant increase in rates of induction of labour with increasing obesity class, and a significantly increased Caesarean section rate with higher BMI Obstetrical care providers should counsel obese patients about the risks they face and the importance of weight loss before pregnancy.     

Cerebral palsy and chorioamnionitis: the inflammatory cytokine link.

Cerebral palsy remains a significant cause of perinatal morbidity in medically developed countries. Human epidemiologic data suggest a relationship between cerebral palsy and chorioamnionitis mediated by proinflammatory cytokines. This association has been confirmed by experimental data from human and animal research that demonstrate an increase in cytokine levels in the amniotic fluid of cases of white matter damage. Recent evidence suggests this damage is the result of a fetal inflammatory response initiated in response to placental inflammation. The strong association between cerebral palsy and chorioamnionitis warrants additional investigation into the mechanisms by which white matter damage is initiated and into possible neuroprotective treatments to prevent the development of cerebral palsy.     

Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status

Summary The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63–0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93–1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54–0.88), p-trend = 0.01) than ER− tumors (0.89 (0.67–1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status.     

Association of breast cancer risk loci with breast cancer survival

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over‐all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta‐analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1‐rs3817198 was significantly associated with improved OS (HR_per‐allele=0.70; 95% CI: 0.58–0.85; p_trend = 2.84 × 10^?4; HR_{heterozygotes} = 0.71; 95% CI: 0.55–0.92; HR_homozygotes = 0.48; 95% CI: 0.31–0.76; p_2DF = 1.45 × 10^?3). In silico, the C allele of LSP1‐rs3817198 was predicted to increase expression of the tumor suppressor cyclin‐dependent kinase inhibitor 1C (CDKN1C). In the meta‐analysis, TNRC9‐rs3803662 was significantly associated with increased death hazard (HR_META =1.09; 95% CI: 1.04–1.15; p_trend = 6.6 × 10^?4; HR_{heterozygotes} = 0.96 95% CI: 0.90–1.03; HR_homozygotes = 1.21; 95% CI: 1.09–1.35; p_2DF=1.25 × 10^?4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1‐rs3817198 and TNRC9‐rs3803662.     

Cluster analysis using physical performance and self-report measures to identify shoulder injury in overhead female athletes

Objectives

To evaluate the diagnostic validity of the Kerlan-Jobe orthopedic clinic shoulder and elbow score (KJOC) and the Closed kinetic upper extremity stability test (CKCUEST) to assess functional impairments associated with shoulder injury in overhead female athletic populations.

Pseudoaneurysm detection with Tc-99m-labeled red blood cells

A technique for the noninvasive diagnosis of pseudoaneurysms is described. This method employs in vivo labeling of red blood cells with Tc-99m to allow better delineation of the vascular anatomy than standard radionuclide angiography. Four cases are illustrated.