The HER-2/neu gene is a proto-oncogene that is amplified in 10-30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p<0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p<0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p=0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p=0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.
Respiratory dysfunction remains one of the most common causes of death in patients with complicated Parkinson's disease (PD). The aim of this study was to investigate pulmonary function in fluctuating PD patients during "on" and "off" states of the disease. We studied 12 fluctuating, non-smoking PD patients (H&Y stages 3-5) without a history of lung or cardiovascular disease; all patients underwent Hoehn and Yahr scale (H&Y) and Unified Parkinson Disease Rating Scale (UPDRS items 18-31) to evaluate extrapyramidal impairment, as well as pulmonary function tests (PFT) and arterial blood gas analyses to assess respiratory function. All evaluations were performed during a stable on state of disease and in an off state produced by 12 hours of therapy withdrawal. A restrictive pattern of flow-volume loop was observed both in on and off states of disease. In the off state, we found a significant worsening in both FEV1 and FVC; the FEV1/FVC ratio was unmodified. These results suggest a restrictive pattern of flow-volume loop in these patients.
Physical examination (PE), mammography (MG), breast MRI, FDG-PET and pathologic evaluation are used to assess primary breast cancer. Their accuracy has not been well studied in patients receiving neoadjuvant chemotherapy. Accuracies of each modality in tumor and nodal assessment in patients with T3/4 tumors receiving neoadjuvant chemotherapy were compared. METHODS-45 patients of a prospective clinical trial studying T3-T4M0 tumors were included. Patients received neoadjuvant chemotherapy: docetaxel/carboplatin with or without trastuzumab before and/or after surgery (depending on HER-2/neu status and randomization). Tumor measurements by PE, MG, and MRI and nodal status by PE and PET were obtained before and after neoadjuvant chemotherapy. Concordance among different clinical measurements was assessed and compared with the tumor and nodal staging by pathology. Spearman corr (r) and root mean square error (RMSE) were used to measure the accuracy of measurements among all modalities and between modalities and pathological tumor size. RESULTS-Comparing to the tumor size measured by PE, MRI was more accurate than MG at baseline (r 0.559, RMSE 35.4% vs. r 0.046, RMSE 66.1%). After neoadjuvant chemotherapy, PE correlated better with pathology than MG or MRI (r 0.655, RMSE 88.6% vs. r 0.146, RMSE 147.1% and r 0.364, RMSE 92.6%). Axillary nodal assessment after neoadjuvant chemotherapy showed high specificity but low sensitivity by PET and PE. CONCLUSION-Findings suggested that MRI was a more accurate imaging study at baseline for T3/T4 tumor and PE correlated best with pathology finding. PET and PE both correctly predicted positive axillary nodes but not negative nodes.
10515 Background: A phase II clinical trial was conducted to study the safety and efficacy of neoadjuvant docetaxel/carboplatin (T/C) with or without trastuzumab (H) in women with stage III breast cancer. Methods: Forty-eight of 75 planned primary breast cancer patients (T3 or T4, any N, M0), age between 18 and 80 have been enrolled. Four cycles of T (75 mg/m2) + C (AUC 6) were given every 3 weeks preoperatively. Patients with HER-2 amplified tumors (FISH +) were randomized to receive either weekly concurrent H or T/C alone preoperatively and T/C plus H postoperatively. Tumors were assessed clinically at baseline and after neoadjuvant therapy. Cardiac assessment consisted of medical history, EKG and LVEF (by echocardiogram or MUGA) at baseline and at the end of neoadjuvant chemotherapy. Results: Available data from 45 of 48 enrolled patients showed 49% (22 cases) with complete clinical response, with 54.5% being HER-2 (+) (12 cases). Stable disease was seen in one patient who was HER-2 (−) (2.2%). Of 37 with complete pathology verification, 11 (29.7%) showed pathologic complete response (pCR) of the primary tumor with 5 cases being HER-2 (+). Of the 22 HER-2 (+) cases that completed neoadjuvant treatment, 11 received T/C/H and 11 received T/C. pCR was noted in 36.4% of the T/C/H group and 9% of the T/C group. LVEF data is available from 43 patients during the neoadjuvant phase, showing 18.6% (8 cases) with decrease of ≥ 10% (5 patients in the T/C arm and 3 patients in the T/C/H arm), although none had cardiac symptoms or LVEF below the normal limit. Conclusions: T/C ± H is clinically active in patients with locally advanced breast cancer including a 30% pCR rate. The cardiotoxicity rates were comparable between patients who received T/C and T/C/H. No significant financial relationships to disclose.
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