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Chris Bajdik

Publications and source records attributed to Chris Bajdik.

4 recordsLinked to original sources

Molecular predictive factors in patients receiving trastuzumab-based chemotherapy for metastatic disease.

BACKGROUND: Trastuzumab-based chemotherapy can improve median survival in the metastatic setting when used in patients with cancer that overexpresses HER2/neu. In addition to HER2 expression, other molecular markers are needed to better predict outcomes after the initiation of trastuzumab-based chemotherapy and to elucidate potential mechanisms of resistance to trastuzumab. PATIENTS AND METHODS: Patients with clinical documentation of HER2/neu-overexpressing metastatic breast cancer treated with trastuzumab between 1998 and 2004 were identified from the British Columbia Provincial Pharmacy Database. Tissues were obtained for microarray analysis of 153 of 306 patients who fit our clinical criteria. Tissue microarrays were constructed for the analysis of multiple molecular factors, and results were correlated to clinical outcomes. Immunohistochemistry was performed on the microarray specimens, and results were correlated with survival and time to progression. RESULTS: Factors commonly associated with poor prognosis in the metastatic setting in general, including short disease-free intervals, high tumor grade, and low estrogen receptor status, were all associated with poor survival in this population with HER2 overexpression. Overexpression of HER3 was observed in 9% of specimens and was associated with a trend toward worse overall survival (P = 0.1). HER3 expression was not correlated with a significant difference in time to progression but did trend to predict for worse survival after progression (P = 0.06). In multivariate analysis, tumor grade and HER3 expression were significantly predictive of overall survival. Phosphatase and tensin homologue status did not appear to correlate with response or survival. CONCLUSION: Our findings suggest that prognosis after initiation of trastuzumab-based chemotherapy depends, in part, on coexpression of HER3.

Antibodies, Monoclonal↗

Hierarchical clustering analysis of tissue microarray immunostaining data identifies prognostically significant groups of breast carcinoma.

Prognostically relevant cluster groups, based on gene expression profiles, have been recently identified for breast cancers, lung cancers, and lymphoma. Our aim was to determine whether hierarchical clustering analysis of multiple immunomarkers (protein expression profiles) improves prognostication in patients with invasive breast cancer. A cohort of 438 sequential cases of invasive breast cancer with median follow-up of 15.4 years was selected for tissue microarray construction. A total of 31 biomarkers were tested by immunohistochemistry on these tissue arrays. The prognostic significance of individual markers was assessed by using Kaplan-Meier survival estimates and log-rank tests. Seventeen of 31 markers showed prognostic significance in univariate analysis (P < or = 0.05) and 4 markers showed a trend toward significance (P < or = 0.2). Unsupervised hierarchical clustering analysis was done by using these 21 immunomarkers, and this resulted in identification of three cluster groups with significant differences in clinical outcome. chi2 analysis showed that expression of 11 markers significantly correlated with membership in one of the three cluster groups. Unsupervised hierarchical clustering analysis with this set of 11 markers reproduced the same three prognostically significant cluster groups identified by using the larger set of markers. These cluster groups were of prognostic significance independent of lymph node metastasis, tumor size, and tumor grade in multivariate analysis (P=0.0001). The cluster groups were as powerful a prognostic indicator as lymph node status. This work demonstrates that hierarchical clustering of immunostaining data by using multiple markers can group breast cancers into classes with clinical relevance and is superior to the use of individual prognostic markers.

Adult↗

The presence of stromal mast cells identifies a subset of invasive breast cancers with a favorable prognosis.

Tissue microarrays containing 348 cases of invasive breast carcinoma were studied by immunohistochemical staining for CD-117, CD-3, CD-20, CD-68, Her2, estrogen receptor protein, and progesterone receptor protein, and results were correlated with patient outcome. Hormone receptor status (both estrogen receptor and progesterone receptor) correlated with a good outcome while Her2 overexpression was associated with a poor outcome. The presence of mast cells in the stroma, as demonstrated by positive c-kit (CD-117) staining, correlated with a good prognosis (P=0.0036). On subset analysis, this association between the presence of mast cells and favorable prognosis was present in the node-negative patients (P=0.018). The presence of mast cells showed an inverse correlation with the presence of CD-68 positive macrophages. No correlation was observed between the presence of mast cells and either B-cells (CD20-positive) or T-cells (CD3-positive). The presence of stromal mast cells was of prognostic significance independent of nodal status and tumor size (P=0.02). When the multivariate analysis was expanded to include tumor grade, estrogen receptor status and Her2 status, as well as tumor size and nodal status, the presence of stromal mast cells approached significance as an independent prognostic indicator.

Adult↗

Comparison of cancer incidence in Iran and Iranian immigrants to British Columbia, Canada.

Migrant studies provided strong evidence about the role of environment and life style in cancer risk. Iran has experienced many immigrants to other countries with different cultures and environment. This study compares cancer incidence rates in Iran, Iranian immigrants to British Columbia (BC), Canada, and the BC general population. Cancer incidence rates were computed from two population-based cancer registries in Iran and from the BC cancer registry. A listing of common Iranian surnames and given names was produced to identify Iranian immigrants within the BC cancer registry. Age-standardized rates (ASRs) were calculated using mid year census data. The overall cancer incidence rate for Iranian female immigrants was intermediate between rates for Iran and the BC general population, and the rate for Iranian male immigrants was lower as compared to the other population groups. For female Iranian immigrants, the incidence of breast cancer was increased four-fold, and for colorectal cancer two-fold, as compared to Iranian rates. A dramatic decrease was found in the incidence of both stomach and oesophageal cancers for Iranian immigrants of both sexes. For male Iranian immigrants, the incidence of prostate cancer was increased as compared to Iranian rates. Differences in incidence rates of specific cancers were observed between BC Iranian immigrants and Iran, with cancer patterns in Iranian immigrants being more similar to the BC general population. This warrants further investigation into differences in lifestyle and cancer detection.

Adolescent↗