Foreign Body in the Airway a Female Patient with Myasthenia Gravis.

Aspiration of a foreign body occurs rarer in adults than it does in children. Advanced age and swallowing disorders, often caused by neuromuscular diseases, predispose for aspiration. Symptoms due to aspiration are mainly cough and wheezing. However, clinical and radiological symptoms may mistakenly suggest lung cancer. Making a proper diagnosis could be difficult and time consuming. In this study we report a case of a 73-year old woman who has been diagnosed and treated myasthenia gravis for 10 years. The patient manifested chronic cough for over a year, weight loss, lung lesions on chest X-ray and computed tomography images in the form of atelectasis and inflammatory infiltrations. The results of cytological tests of bronchoalveolar lavage fluid were 'atypical cells' which suggested a lung cancer. Flexible bronchoscopy set the diagnosis as a foreign body in right upper bronchus, which turned out to be a piece of a plant obstructing the bronchus. The patient came down with pneumonia. Laboratory examinations revealed leucocytosis and a high level of C-reactive protein. A complete removal of foreign body took place during rigid bronchoscopy. Concomitantly, but unrelated to the finding of a foreign body in the bronchus, the patient was diagnosed with digestive tract perforation on the basis of X-ray images, which remained otherwise asymptomatic. Explorative laparotomy revealed a perforated colonic diverticulum, which was successfully treated surgically.

PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy.

Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used. The vast majority of breast carcinomas expressed high level of nuclear PARP-1 protein and a small percentage of tumors exhibited both nuclear and cytoplasmic PARP-1 expression. There was a significant difference between the mean nuclear PARP-1 quickscore in BRCA1-associated versus BRCA1-non-associated carcinomas in all tumors (P < 0.0001), in the basal-like group (P = 0.0086), TN (P = 0.0015), and non-basal-like groups (P = 0.016) but not in the non-TN group. Among BRCA1-associated BCs, low PARP-1 expression was found in 18.5% of all cases, 18.9% of basal-like and 21% of TN cancers. Among BRCA1-non-related tumors, low PARP-1 expression was found in 8.8% of all cases, 3.1% of basal-like, and 2.7% of TN cancers. PARP-1 expression is significantly associated with BRCA1 status in basal-like and TN BCs. The assessment of PARP-1 expression in tumor samples may improve the selection of BC patients for PARP inhibitor therapy.

Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer.

PURPOSE: To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer. PATIENTS AND METHODS: A total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model. RESULTS: Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75). CONCLUSION: The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.

Immunophenotypic predictive profiling of BRCA1-associated breast cancer.

The immunophenotypic predictive profile of BRCA1-associated cancers including major predictive markers, i.e., PARP-1, EGFR, c-kit, HER-2, and steroid hormones (ER/PR) that may have therapeutic relevance has not yet been reported in a comprehensive study. Using immunohistochemistry, we examined the expression of these proteins in a large cohort of BRCA1-associated breast cancers. PARP-1 immunoreactivity was found in 81.9%, EGFR in 43.6%, ER/PR in 17.9%, c-kit in 14.7%, and overexpression of HER-2 in 3.6% of cancers. For all markers studied, 8.2% of tumors were negative. Expression of only one predictive marker was found in 29.7% of cancers, and most frequently, it was PARP-1 (20.8%). In 62.1% of tumors, more than one predictive marker was expressed: PARP-1 and EGFR in 30.4%, PARP-1, and hormone receptors in 13.3% and PARP-1 with c-kit in 7.5% of all tumors. Coexpression of two or more other predictive markers was rare. There were significant differences in the median age at diagnosis of BRCA1-associated cancer between patients with ER+ vs. ER- and grades 1-2 vs. grade 3 tumors. These results demonstrate that BRCA1-associated cancers differ with respect to expression of proteins that are regarded as targets for specific therapies and that 92% of patients with BRCA1-associated cancers may benefit from one or several options for specific therapy (in addition to DNA damaging agents, e.g., cisplatin). About 8% of cancers which do not express therapeutic target proteins may not respond to such therapies. Knowledge of the immunophenotypic predictive profile may help with the recruitment of patients for trials of targeted therapies.