BRCA mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees

Objective:As prostate cancer (PrC) shows a BRCA mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the BRCA mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among BRCA1 and BRCA2 carriers.Methods:Following the Modena criteria for the BRCA test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ²) test and Kaplan–Meier methods, respectively.Results:Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for BRCA and one for CHEK2 genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the BRCA2 gene fell in the prostate cancer cluster region (PCCR) at the 3′ terminal of the 7914 codon.Conclusions:It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in BRCA2 carriers.     

Invasion in breast lesions: the role of the epithelial–stroma barrier

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in‐situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non‐infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM‐like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.     

A striving for independence: a qualitative study of women living with vertebral fracture

Background  

Quantitative studies using generic and disease-specific health-related quality of life (HRQOL) questionnaires have shown that osteoporosis-related vertebral fractures have a significant negative effect on HRQOL, but there are only few studies that address what it means to live with vertebral fracture from a deeper experiential perspective. How HRQOL and daily life are affected several years after vertebral fracture and how women cope with this are more unclear. This study aimed to describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis.     

Changes in Hip Fracture Epidemiology: Redistribution Between Ages, Genders and Fracture Types

After several reports of increasing hip fracture incidence some studies have suggested a trend-break. In a previous study of hip fractures we forecast a 70% increase in the total number of fractures from 1985 up to year 2000. We therefore studied the incidence trend for the last 15 years and supply a new prognosis up to year 2010. We recorded all incident hip fractures treated in the county of ?sterg?tland, Sweden (≈ 400 000 inhabitants) 1982–96. A total of 11 517 hip fractures in men and women aged 50 years and above were included in the study after cross-validation between a computerized register of radiologic investigations and the hospital records. The projected number of fractures up to year 2010 was estimated by a Poisson regression model, considering both age and year of fracture in every single year 1982–96 for the respective fracture type and gender, and applied to the projected population. The annual number of hip fractures increased by 39% in men and 25% in women during the study period. Amongst men, the age-adjusted incidence of cervical fractures increased from 188 to 220/100 000 and of trochanteric fractures from 138 to 170/100 000. In women the incidence of cervical fractures decreased from 462/100 000 to 418/100 000 and of trochanteric fractures from 407/100 000 to 361/100 000. Cervical/trochanteric fracture incidence rate ratio leveled off, and also the female/male fracture rate ratio declined. A prognosis assuming that the incidence development will continue as during 1982–96, and a population in agreement with the forecast, predicts that the total age- and sex-adjusted number of hip fractures will decrease by 11% up to year 2010 compared with 1996. In women and men, however, a decrease of 19% and an increase of 7% respectively were projected. If the age- and sex-specific incidence remains at the same level as at the end of the study period, no significant change in the total numbers will occur. A trend-break was thus found in hip fracture incidence for women but not for men. Whether this is due to therapeutic and/or preventive measures in women is unknown. According to the most probable scenario a substantial increase in male trochanteric fractures (36%) is expected up to 2010, while all other hip fractures in both genders will decrease by 4–32% resulting in a total reduction of 11%. Received: 17 November 2000 / Accepted: 2 July 2001     

Increased fibrinogen levels are associated with persistentChlamydia pneumoniaeinfection in unstable coronary artery disease

Aim Increased levels of acute phase proteins, e.g. fibrinogen, arerelated to a poor outcome in unstable coronary artery disease,but the cause of inflammation is unknown. We therefore investigatedthe prevalence of persistent Chlamydia pneumoniae infection,and its relationship to inflammation in this condition. Methods and Results In 256 patients participating in the FRISC trial, evaluatingthe effects of dalteparin (a low molecular weight heparin) inunstable angina or non-Q wave myocardial infarction, Chlamydiapneumoniae IgA antibody titres and levels of fibrinogen, C-reactiveprotein and troponin T were determined at inclusion. IncreasedC. pneumoniae IgA antibody titres were significantly more commonin the patients (36%) than in a reference popu-lation of similarage (19%); P<0·001. Raised titres were associatedwith male gender, increasing age, smoking, and elevated concentrationsof fibrinogen, C-reactive protein and troponin T. The associationbetween persistent C. pneumoniae infection and increased fibrinogenlevels was independent of other risk factors evaluated in multivariateanalysis (P=0·009). Conclusion Persistent C. pneumoniae infection is common in unstable coronaryartery disease. The independent association between increasedC. pneumoniae IgA antibody titres and fibrinogen levels indicatesthat chronic infection could be of importance for disease activity.