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Purpose: The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer., Methods and Materials: A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used., Results: A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields., Conclusion: This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results.

The GABA(B) receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABA(B)R1 and GABA(B)R2. In this study, the cellular distribution of the GABA(B)R1 and GABA(B)R2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The results showed that the GABA(B) receptor subunits GABA(B)R1 and GABA(B)R2 were both found on the same neurons and followed the same distribution patterns. In the striatum, these subunits were found on the five major types of interneurons based on morphology and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the projection neurons (type 4). In the globus pallidus, intense GABA(B)R1 and GABA(B)R2 subunit labeling was found in large pallidal neurons, and in the substantia nigra, both pars compacta and pars reticulata neurons were labeled for both receptor subunits. Studies investigating the colocalization of the GABA(A) alpha(1) subunit and GABA(B) receptor subunits showed that the GABA(A) receptor alpha(1) subunit and the GABA(B)R1 subunit were found together on GABAergic striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD neurons) and on neurons in the globus pallidus and substantia nigra pars reticulata. GABA(B)R1 and GABA(B)R2 were found on substantia nigra pars compacta neurons but the GABA(A) receptor alpha(1) subunit was absent from these neurons. The results of this study provide the morphological basis for GABAergic transmission within the human basal ganglia and provides evidence that GABA acts through both GABA(A) and GABA(B) receptors. That is, GABA acts through GABA(B) receptors, which are located on most of the cell types of the striatum, globus pallidus, and substantia nigra. GABA also acts through GABA(A) receptors containing the alpha(1) subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata., (Copyright 2004 Wiley-Liss, Inc.)

Analysis of interactions between the C-terminal tail of the MOP-1 and MOP-1A variants of the human mu-opioid receptor with proteins derived from a human brain cDNA library resulted in identification of the actin and intermediate filament-binding protein periplakin. Mapping of this interaction indicated that the predicted fourth intracellular loop/helix VIII of the receptor interacts with the C-terminal rod and linker region of periplakin. Periplakin is widely expressed in the central nervous system of both man and rat and demonstrated an overlapping but not identical distribution with mu-opioid (MOP) receptors. Co-expression of periplakin with MOP-1 or a MOP-1-eYFP fusion construct in HEK293 cells did not interfere with agonist-mediated internalization of the receptor. When co-expressed with a MOP-1-Gi1 alpha fusion protein periplakin significantly reduced the capacity of the agonist to stimulate binding of 35S-labeled guanosine 5'-3-O-(thio)triphosphate ([35S]GTP gamma S) to the receptor-associated G protein. By contrast, periplakin did not interfere with agonist-stimulation of [35S]GTP gamma S binding to either an alpha 2A-adrenoreceptor-Gi1 alpha fusion protein or a beta2-adrenoreceptor-Gs alpha fusion protein, indicating its selectivity of function. This represents the first example of an opioid receptor-interacting protein that functions to disrupt agonist-mediated G protein activation.

Background: Multiple treatment guidelines and practice standards have been developed regarding the management of patients with breast carcinoma. Few evaluations of the penetration and utility of these practice standards have been performed. In 1992, the American College of Surgeons (ACOS), the American College of Radiology, the College of American Pathologists, and the Society of Surgical Oncology collaborated in establishing standards for breast-conservation treatment (BCT). The authors sought to determine whether practice patterns for patients with breast carcinoma who underwent BCT were consistent with these standards 2 years after their dissemination and to establish whether compliance varied by the same patient and hospital variables that predicted for the amount of BCT performed., Methods: A study specific questionnaire was circulated to cancer registrars through the Commission on Cancer of the ACOS asking them to submit reports on patients with Stage I and II breast carcinoma who were diagnosed in 1994. Eight hundred forty-two predominantly community hospitals throughout the United States responded, yielding a total of 16,643 analyzable patients. The frequency of compliance to the 1992 published practice standards for 7097 patients who received BCT was determined. The variation in compliance rates by patient age, race, and insurance status and the treating hospital's geographic locations and cancer programs were evaluated., Results: Of the 22 standards that were evaluated in the areas of preoperative mammography (2 standards), labeling of the surgical specimen (3 standards), pathology report content (10 standards), radiation after lumpectomy (6 standards), and systemic therapy for patients with positive lymph nodes (1 standard), treatment adherence was > or = 80% for 16 standards (73%). Poor compliance was demonstrated for six standards: the documentation of an abnormality's size in the mammogram report, labeling the lumpectomy specimen with the affected quadrant of the breast, spatial orientation of the lumpectomy specimen and inclusion of lymphatic/vascular invasion, ductal carcinoma in situ, and macroscopic margin assessment in the pathology report. Variation in compliance to a standard occurred frequently across the type of hospital cancer program and geographic region (77% for both), and variation occurred less across the patient variables of age (32%), race (41%), and payer (23%). There was not a pattern of more frequent compliance among variables associated with more BCT use., Conclusions: Large-scale evaluation of the penetration of treatment standards is feasible. For patients who underwent lumpectomy, practice appeared to be consistent (> or = 80% compliance), with 73% of 22 treatment standards evaluated. The standards with poor compliance represent areas for targeted physician education and reevaluation. Significant differences in adherence to a standard were seen frequently based on a hospital's geographic location and type of cancer program. This emphasizes the importance of adequate dissemination of treatment standards to ensure penetration into medical practices of all types., (Copyright 2003 American Cancer Society)