The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years

The BRCA2 N372H nonconservative amino acid substitution polymorphism appears to affect fetal survival in a sex-dependent manner, and the HH genotype was found to be associated with a 1.3-fold risk of breast cancer from pooling five case-control studies of Northern European women. We investigated whether the BR 2 N372H polymorphism was associated with breast cancer in Australian women using a population-based case-control design. The BRCA2 372 genotype was determined in 1397 cases under the age of 60 years at diagnosis of a first primary breast cancer and in 775 population-sampled controls frequency matched for age. Case-control analyses and comparisons of genotype distributions were conducted using logistic regression. All of the statistical tests were two-tailed. The HH genotype was independent of age and family history of breast cancer within cases and controls, and was more common in cases (9.2% versus 6.5%). It was associated with an increased risk of breast cancer, 1.47-fold unadjusted (95% confidence interval, 1.05-2.07; P = 0.02), and 1.42-fold (95% confidence interval, 1.00-2.02; P = 0.05) after adjusting for measured risk factors. This effect was still evident after excluding women with any non-Caucasian ancestry or the 33 cases known to have inherited a mutation in BRCA1 or BRCA2, and would explain similar to3% of breast cancer. The BRCA2 N372H polymorphism appears to be associated with a modest recessively inherited risk of breast cancer in Australian women. This result is consistent with the findings for Northern European women.

Occult Axillary Lymph Node Metastases in Breast Cancer Do Matter: Results of 10-Year Survival Analysis

Axillary lymph node status is one of the most powerful prognostic factors for patients with breast cancer and is often critical in stratifying patients into adjuvant treatment regimens. In 203 apparently node-negative cases of breast cancer, a combination of immunohistochemical staining and step-sectioning identified occult metastases in 25% of cases. Ten-year follow-up information is available for these patients. Histologic features of the primary tumor and immunohistochemical staining for estrogen receptor, progesterone receptor, Her-2, and p53 were also evaluated. With multivariate analysis, both occult metastases and higher histologic grade of the primary tumor were independent predictors of disease-free survival. Histologic grade was the only significant independent predictor of overall survival. Estrogen receptor, progesterone receptor, Her-2, and p53 status did not predict the presence of metastases or survival when all tumor types were considered together. Metastases >0.5 mm significantly predicted a poorer disease-free survival when invasive ductal carcinomas were considered alone. Histologic grade was significantly associated with disease-free survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients. The presence of occult metastases approached significance for overall survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients.

Shoulder movement after breast cancer surgery: results of a randomised controlled study of postoperative physiotherapy

Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer. This study investigated changes in shoulder movement after surgery for primary, operable breast cancer to determine the effect of elective physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were completed preoperatively, at day 5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG. The TG women had 14degrees more abduction at 3 months and 7degrees at 24 months. Functional recovery at 1 month was greater in those randomised to the TG, with a dominant operated arm (OA) or receiving breast-conserving surgery. However, it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman's recovery at 1 month postoperatively. The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed. The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery.

Physiotherapy after breast cancer surgery: results of a randomised controlled study to minimise lymphoedema

The development of secondary arm lymphoedema after the removal of axillary lymph nodes remains a potential problem for women with breast cancer. This study investigated the incidence of arm lymphoedema following axillary dissection to determine the effect of prospective monitoring and early physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were made preoperatively, at day 5 and at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. Using this definition, the incidence of lymphoedema at 24 mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated an increase of at least 200 ml in the VOL of the operated arm compared to the unoperated arm. The physiotherapy intervention programme for the TG women included principles for lymphoedema risk minimisation and early management of this condition when it was identified. These strategies appear to reduce the development of secondary lymphoedema and alter its progression in comparison to the CG women. Monitoring of these women is continuing and will determine if these benefits are maintained over a longer period for women with early lymphoedema after breast cancer surgery.

Second primary oesophageal cancer following radiation for breast cancer

The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER-2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC. (C) 2003 Elsevier Science Ltd. All rights reserved.

Model-based clustering in gene expression microarrays: An application to breast cancer data

In microarray studies, the application of clustering techniques is often used to derive meaningful insights into the data. In the past, hierarchical methods have been the primary clustering tool employed to perform this task. The hierarchical algorithms have been mainly applied heuristically to these cluster analysis problems. Further, a major limitation of these methods is their inability to determine the number of clusters. Thus there is a need for a model-based approach to these. clustering problems. To this end, McLachlan et al. [7] developed a mixture model-based algorithm (EMMIX-GENE) for the clustering of tissue samples. To further investigate the EMMIX-GENE procedure as a model-based -approach, we present a case study involving the application of EMMIX-GENE to the breast cancer data as studied recently in van 't Veer et al. [10]. Our analysis considers the problem of clustering the tissue samples on the basis of the genes which is a non-standard problem because the number of genes greatly exceed the number of tissue samples. We demonstrate how EMMIX-GENE can be useful in reducing the initial set of genes down to a more computationally manageable size. The results from this analysis also emphasise the difficulty associated with the task of separating two tissue groups on the basis of a particular subset of genes. These results also shed light on why supervised methods have such a high misallocation error rate for the breast cancer data.

Cost of diseases in Brazil: breast cancer, enteritis, cardiac valve disease and bronchopneumonia

The results from the need to develop methodologies for performing cost analysis in developing countries, principally in the region of Latin America, were studied. It, furthermore, serves to generate knowledge from an economic evaluation in order to support decision-making related to the organization of health systems, particularly in the efficient use of resources which are allocated for the provision of medical services. Two chronic diseases (breast cancer and cardiac valve disease) and two infections (enteritis and bronchopneumonia) were selected for the study. The results recommend the use of a valid methodology for economic cost analysis of any disease to be studied and the use of this information in the decision-making process.

Breast cancer in Mexican women: an epidemiological study with cervical cancer control

INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer deaths in women, with increasing incidence and mortality in recent years. Therefore, the aim of the study is identify possible risk factors related to BC. METHODS: An epidemiological study of hospital cases of BC and controls with cervical uterine cancer (CUCA) was carried out at eight third level concentration hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls with CUCA were identified among women younger than 75 years who had been residents of the metropolitan area of Mexico City for at least one year. Diagnosis was confirmed histologically in both groups. Variables were analyzed according to biological and statistical plausibility criteria. Univariate, bivariate and multivariate analyses were carried out. Cases and controls were stratified according to the menopausal hormonal status (pre and post menopause). RESULTS: The factors associated with BC were: higher socioeconomic level (OR= 2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the duration of the breastfeeding period was a protective factor (>25 months: OR= 0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the identification of risk factors for BC described in the international literature, in the population of Mexican women. Breastfeeding appears to play an important role in protecting women from BC. Because of changes in women`s lifestyles, lactation is decreasing in Mexico, and young women tend not to breastfeed or to shorten the duration of lactation.

RC-IAL cell line: sensitivity of rubella virus grow

OBJECTIVE: The rapid growth of the rubella virus in RC-IAL² with development of cytopathic effect, in response to rubella virus infection, is described. For purposes of comparison, the rubella virus RA-27/3 strain was titered simultaneously in the RC-IAL, Vero, SIRC and RK13 cell lines. METHODS: Rubella virus RA-27/3 strain are inoculated in the RC-IAL cell line (rabbit Kidney, Institute Adolfo Lutz). Plates containing 1.5x10(5) cells/ml of RC-IAL line were inoculated with 0.1ml s RA-27/3 strain virus containing 1x 10(4)TCID50/0.1ml. A 25% cytopathic effect was observed after 48 hours and 100% after 96 hours. The results obtained were compared to those observed with the SIRC, Vero and RK13 cell lines. Rubella virus was detected by immunohistochemistry. RESULTS: With the results, it was possible to conclude that the RC-IAL cell line is a very good substrate for culturing rubella virus. The cells inoculated with rubella virus were examined by phase contrast microscopy and showed the characteristic rounded, bipolar and multipolar cells. The CPE in RC-IAL was observed in the first 48 hours and the curve of the increased infectivity was practically the same as observed in other cell lines. CONCLUSIONS: These findings are important since this is one the few cell lines described in the literature with a cytopathic effect. So it can be used for antigen preparation and serological testing for the diagnosis of specific rubella antibodies.