B. C. Turner

Thomas Jefferson University, Filadelfia, Pennsylvania, United States

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Publications (19)

  • AG Wernicke · EC Pequignot · L KOMARNICKY · [...] · BC Turner
    Article · Sep 2004 · International Journal of Radiation OncologyBiologyPhysics
  • BC Turner · Q Ren · G Liu · [...] · JP Palazzo
    [Show abstract] [Hide abstract] ABSTRACT: Many breast cancer patients present with locally metastatic disease in the axillary lymph nodes. The determination of disease in the axillary lymph nodes is critical since these patients often have compromised survival rates and require systemic chemotherapy. The use of an axillary lymph node dissection and sentinel lymph node evaluation is effective in the diagnostic ability to determine the status of the axillary lymph nodes but is associated with toxicity and often is not completely reliable indicator of disease in the lymph nodes. Gene expression patterns in the primary breast tumor may be helpful in evaluating the risk of metastatic disease in the axillary lymph nodes and identify potential drug targets for these women. Total RNA from 16 women having benign breast tissue (5 patients), pathologic stage T1/T2NOMO (6 patients), and pathologic stage T1/T2NIMO (5 patients) was isolated from the benign breast tissue or the breast tumor using a modified Trizol technique. The isolated RNA was amplified by TT-based RNA amplification and the amplified RNA was labeled with either Cy5 (breast tumor or benign breast tissue) or Cy3 (MCF10A-normal breast cell line) followed by hybridization on glass slide microarrays containing 19,000 human genes or expressed sequence tags. Analysis of the arrays was performed using QuantArray software and cluster analysis using an agglomerative hierarchical clustering algorithm patterns. Permutation analysis of classification functions revealed that gene-expression profiles of breast tumors from benign breast tissue, lymph node positive breast tumors, and lymph node negative breast tumors demonstrated significant differences (p=0.003). There was overlap in gene expression patterns between lymph node positive and negative breast tumors but distinct differences in patterns of gene expression could accurately identify those breast cancer patients found to have metastatic disease in the axillary lymph nodes. Many of the genes identified have not been previously suggested to have role in metastatic disease. Our results reveal that microarray gene expression patterns may identify breast cancer patients with metastatic disease in the axillary lymph nodes and reveal genes important in the development of metastatic disease that may serve as novel targets for drug development.
    Article · Jan 2001 · Breast Cancer Research and Treatment
  • B. C Turner · Q Ren · P Gupta · [...] · S Haldar
    Article · Dec 2000 · International Journal of Radiation OncologyBiologyPhysics
  • C. S Kim · A. A Gumbs · L Komarnicky · [...] · B. C Turner
    Article · Dec 2000 · International Journal of Radiation OncologyBiologyPhysics
  • B C Turner · AA Gumbs · C J Carbone · [...] · B G Haffty
    [Show abstract] [Hide abstract] ABSTRACT: The p53 tumor suppressor gene encodes a nuclear phosphoprotein that is thought to be important to cell cycle regulation and DNA repair and that also may regulate induction of apoptosis by ionizing radiation. Somatic p53 gene mutations occur in 30-50% of breast carcinomas and are associated with poor prognosis. Mutations in the p53 gene result in prolonged stability of the protein that can be detected by immunohistochemical techniques. In a matched case-control study of breast carcinoma patients with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy, the authors investigated the frequency and prognostic significance of somatic p53 mutations as well as the clinical characteristics of patients with these mutations. Between 1973 and 1995, there were 121 breast carcinoma patients with IBTR following lumpectomy and radiation therapy, and the authors identified 47 patients in whom the paraffin embedded tissue blocks from the primary breast tumors were available for further molecular analysis. Forty-seven control breast carcinoma patients from the breast carcinoma data base were individually matched to the index cases who did not have IBTR for age, treatment date, follow-up, histology, margin status, radiation dose, and adjuvant treatment. Immunohistochemistry using a monoclonal antibody to mutant p53 protein was used to determine mutant p53 protein overexpression in breast tumors and appropriately scored. A total of 12 of 47 tumor specimens (26%) from index patients with breast tumor relapses demonstrated mutant p53 protein overexpression, whereas only 4 of 47 specimens from controls (9%) demonstrated high mutant p53 immunoreactivity (P = 0.02). The authors found that 9 of 23 patients (39%) with early breast tumor recurrences (recurrences within 4 years of diagnosis) had overexpression of mutant p53 protein, whereas only 1 of 23 control cases (4%) had high mutant p53 protein immunoreactivity (P = 0.003). In contrast, index cases from patients with late breast tumor relapses (more than 4 years after diagnosis), which are more likely to represent de novo breast tumors, and control cases from the breast carcinoma data base without IBTR had similar levels of mutant p53 protein overexpression (P = not significant). The 10-year distant disease free survival for patients with mutant p53 protein was 48%, compared with 67% for breast carcinoma patients without detection of mutant p53 protein (P = 0. 08). The authors found that 13 of 14 primary breast tumors (93%) with mutant p53 protein overexpression were estrogen receptor negative (P = 0.01) and 11 of 14 (79%) were progesterone receptor negative (P = not significant). In a matched case-control study, overexpression of mutant p53 protein has prognostic significance with respect to IBTR following lumpectomy and radiation therapy. Breast tumors with p53 mutations are generally estrogen receptor negative and are associated with compromised distant disease free survival.
    Article · Apr 2000 · Cancer
  • S S Yoo · D Carter · B C Turner · [...] · B G Haffty
    [Show abstract] [Hide abstract] ABSTRACT: Recent laboratory experiments have demonstrated that cyclin D1 levels (cycD1) can influence radiosensitivity. The purpose of the current study is to evaluate the prognostic significance of cycD1 for local recurrence in early-stage larynx cancer treated with primary radiation therapy. The study was conducted using a matched case-control design in 60 early-stage (T1-T2/N0) larynx cancer patients. All patients had squamous cell carcinoma of the larynx and were treated with primary radiation to a total median dose of 66 Gy in daily fractions of 2 Gy, without surgery or chemotherapy. Thirty patients who suffered a local relapse in the larynx after treatment served as the index case population. These 30 cases were matched by age, sex, site (glottic vs. supraglottic), radiation therapy technique/dose, and follow-up, to 30 control patients who did not experience a local relapse. Immunohistochemical staining from cycD1 was performed on the paraffin-embedded specimens. The pathologist, blinded to the clinical information, scored each of the specimens on a four-point intensity scale (0 = no stain, 1 = faint, 2 = moderate, 3 = strong) and percent distribution. Patients were considered to be positive for cyclin D1 if the staining was 2+ or greater with a percent distribution of at least 5%. By design of the study, the two groups were evenly balanced with respect to age, sex, stage, radiation dose, and follow-up. CycD1 levels correlated with proliferating cell nuclear antigen levels. Low levels of cycD1 significantly correlated with local relapse; 19/30 (63%) of the index cases stained negative, while only 10/30 (33%) of the control cases stained negative (P = 0.03). These data suggest that low levels of cycD1 correlate with relatively radioresistant early-stage larynx carcinoma. With larger more confirmatory clinical and laboratory data, this data may have significant clinical implications. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 22-28 (2000).
    Article · Mar 2000 · International Journal of Cancer
  • Source
    TA Lehman · B G Haffty · C J Carbone · [...] · B C Turner
    [Show abstract] [Hide abstract] ABSTRACT: Previous studies have determined that the frequency of germ-line p53 mutations in familial breast cancer patients is 1% or less, but these reports have not investigated the importance of polymorphic intron base changes in the p53 gene. Therefore, we investigated the frequency of both exon and intron germ-line p53 base changes in 42 breast cancer patients with a strong family history of breast cancer. The mean age of presentation of these patients was 44.0 years (range, 29-69), and 12 of 42 (29%) were of known Ashkenazi ancestry. Purified DNA obtained from the 42 index cases was screened for germ-line p53 mutations in exons 2-11 and surrounding introns using a combination of intron based primers for PCR-single strand conformation polymorphism analysis, direct sequencing, and microarray sequencing using the Affymetrix p53 gene chip methodology. Morphological analysis of apoptosis and cell survival determination were performed on EBV-immortalized lymphoblastoid cell lines from two patients with the p53 intron 6 mutation. A germ-line mutation in the p53 gene at nucleotide 13964 with a G to C base change (13964GC) was identified in 3 of 42 (7.1%) hereditary breast cancer patients. Two patients were heterozygous for this mutation, and one patient had a homozygous mutation. In comparison, 0 of 171 (0%) of sporadic breast cancer patients had the p53 13964GC mutation (P = 0.0003). We found that 0 of 42 (0%) of these hereditary breast cancer patients had other germ-line p53 mutation in exons 2-11. However, pedigree analysis demonstrated that all three patients had strong family histories of multiple types of cancers consistent with Li-Fraumeni syndrome but with late age of onset. Comprehensive BRCA1 and BRCA2 nucleotide analysis from patients with the p53 13964GC mutation revealed no concomitant deleterious BRCA1 or BRCA2 mutations, although they were found in the other hereditary breast cancer patients. Functional analysis of two immortalized lymphoblastoid cell lines derived from patients with the p53 13964GC mutation demonstrated prolonged in vitro survival in response to cisplatinum treatment and showed decreased chemotherapy-induced apoptosis. Immunohistochemical analysis of breast tumors from these patients revealed high levels of mutant p53 protein, suggesting a functional mutation in the p53 gene. In summary, we have identified a single p53 intron mutation in familial breast cancer patients that is present at elevated frequency and has functional activity.
    Full-text available · Article · Mar 2000 · Cancer Research
  • J. A. Fritzell · P. M. Glazer · B. G. Haffty · [...] · B. C. Turner
    Article · Dec 1999 · International Journal of Radiation OncologyBiologyPhysics
  • B. C. Turner · T. A. Lehman · R. Modali · [...] · B. G. Haffty
    Article · Dec 1999 · International Journal of Radiation OncologyBiologyPhysics
  • T. E. Smith · D. Lee · B. C. Turner · [...] · B. G. Haffy
    Article · Dec 1999 · International Journal of Radiation OncologyBiologyPhysics
  • Source
    B C Turner · P M Glazer · B G Haffty
    Full-text available · Article · Dec 1999 · Journal of Clinical Oncology
  • B.C. Turner · E. Harrold · A.A. Gumbs · [...] · B.G. Haffty
    Article · Dec 1998 · International journal of radiation oncology, biology, physics
  • E V Harrold · B C Turner · E T Matloff · [...] · B G Haffty
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to evaluate the relationships among young age at diagnosis, family history status, and local recurrence in breast cancer patients treated with lumpectomy and radiation therapy. Between January 1970 and December 1990, 984 early-stage breast cancer patients were treated with conservative surgery and radiation therapy at Yale-New Haven Hospital. All patient data, including demographics, staging information, treatment, and outcome variables were entered into a computerized database. The current study focused on the relationships between young age, family history, and local relapse. A group of 52 patients who experienced a local recurrence in the conservatively treated breast and 52 matched control patients who had not experienced a local recurrence were asked to participate in a study to determine whether local recurrence was associated with family history. Detailed family history interviews were conducted, and pedigrees were analyzed by a genetic counselor who was blind to the clinical history of the patients. As of September 1997, with a median follow-up of 12.3 years for the 984 patients in the database, the overall actuarial 10-year survival is 73%, and the 10-year distant metastasis-free survival is 78%. Of the 984 patients, 112 have experienced a local relapse in the conservatively treated breast, resulting in a 10-year actuarial breast relapse rate of 15%. The 10-year survival after breast relapse is 69%. Patient age tested as a continuous variable correlated strongly with ipsilateral breast tumor relapse. Using age 40 as a cutpoint, patients aged 40 years or less had a significantly higher local relapse rate than patients older than 40 years (P < 0.001). Although the relationship between local relapse and young age was strong, no association was found between family history and local relapse in the detailed family history study. Young age at diagnosis was a significant prognostic factor for local relapse. In a detailed family history study using a case-control design, no significant differences in family history status were found between patients who had experienced a local relapse and patients who had not.
    Article · Sep 1998 · The cancer journal from Scientific American
  • B. C. Turner · P. M. Glazer · A. A. Gumbs · [...] · B. G. Haffty
    Article · Dec 1997 · International Journal of Radiation OncologyBiologyPhysics
  • Source
    B C Turner · B G Haffty · L Narayanan · [...] · P M Glazer
    [Show abstract] [Hide abstract] ABSTRACT: The insulin-like growth factor-I receptor (IGF-IR) plays a critical role in cell growth regulation and transformation. The radiosensitivity of NIH 3T3 fibroblasts overexpressing either wild-type or mutant IGF-IR was examined. High levels of wild-type IGF-IR conferred radioresistance, and mutational analysis revealed that this effect correlated with the transforming capacity but not the mitogenic activity of the receptor. The radioresistant phenotype was reversed when the cells were incubated with antisense oligonucleotides targeted to IGF-IR mRNA, demonstrating that IGF-IR directly influences radioresistance. The clinical significance of these findings was examined in an immunohistochemical analysis of primary breast tumors, revealing that high levels of IGF-IR in tumor samples were highly correlated with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy (P = 0.001). Subgroup analysis revealed that, for early breast tumor relapses (within 4 years of initial breast tumor diagnosis), elevated levels of IGF-IR were strongly associated with IBTR (P = 0.004) but IGF-IR expression was not prognostic for IBTR from breast cancer patients with late relapses (P was not significant). These studies provide evidence for the influence of IGF-IR on cellular radioresistance and response to therapy and raise the possibility that the radiocurability of selected tumors may be improved by pharmaceutical strategies directed toward the IGF-IR.
    Full-text available · Article · Sep 1997 · Cancer Research
  • B. C. Turner · B. G. Haffty · D. Carter · [...] · P. M. Glazer
    Article · Dec 1996 · International Journal of Radiation OncologyBiologyPhysics
  • A. A. Gumbs · B. C. Turner · J. P. S. Knisely · [...] · L. D. Wilson
    Article · Dec 1996 · International Journal of Radiation OncologyBiologyPhysics
  • B. C. Turner · B. M. Kacinski · A. Gumbs · [...] · L. D. Wilson
    Article · May 1996 · Radiotherapy and Oncology
  • B.B.C. Turner · E. Harrold · E. Matloff · [...] · Beinfield
    Article ·