Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis.
Purpose: Full bladder at time of simulation and daily treatment is requested of prostate/prostate‐bed patients; however, not all patients comply. This study is to analyze the V65 and V40 changes in correlation with CBCT bladder filling. Methods: Daily 2D KV/KV IGRT using implanted radio‐opaque markers and weekly 3D CBCT IGRT direct visualization of target volume were routinely performed. Physicians compared the pre‐treatment CBCT bladder filling to the planned CT bladder filling to identify the poor bladder fillers. Weekly CBCT bladder volumes were contoured of poor bladder fillers, and VMAT/IMRT plans recalculated to obtain the actual bladder dose, using the commercially available DVH Evaluator to obtain the V65 and V40 values promptly and accurately. Results: From Jan 2012‐Nov 2012, a total of 181 prostate/prostate‐bed patients were analyzed. 47 patients were classified as poor‐average bladder fillers. A total of 358 CBCT bladders were contoured to obtain bladder volumes/doses. The 358 CBCT images were grouped into 10 bins to differentiate bladder volumes from baseline. The median change in V65 and V40 bins were both monotonically increasing for this dataset. Despite this evident trend, no statistically significant correlation in IPSS scores was found in relation to the change in V65 or V40. Conclusions: The V65 <= 25% and V40 <= 50% are among the tightest bladder constraints in common clinical use. Since the image registration aligns the prostate and the daily bladder volumes vary, the resulting tightly conformal plans are robust to daily bladder filling variations. No statistically significant correlation to IPSS score changes were identified thus far in relation to the bladder filling changes. Additional follow‐up is required to ensure that there are no long‐term adverse effects based on poor bladder filling during care. Intellectual property rights for the DVH Evaluator software tool, which was used for this analysis
Unadjusted 5y survival estimates include: chemo+standard RT (82.9%), chemo+high dose (80.5%), chemo+low dose (73.0%), no chemo+standard RT (71.1%), no chemo+high dose (57.8%), no chemo+low dose (51.0%). There was a linear trend towards increased appropriate use of standard RT+chemotherapy with time. Conclusions: Over one-quarter of patients with early stage anal cancer receive radiation doses in excess of 54 Gy and this non-standard practice varied by time, population density, chemotherapy, and tumor size. Analysis is underway to further evaluate outcomes according to radiation dose in the presence and absence of chemotherapy using cubic splines and matching. (S021) A Phase 2 Randomized Double Blinded Study Evaluating the Efficacy of Curcumin With Pre-Operative Chemoradiation for Rectal Cancer
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.