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Chapman J.W.,Queens University | O'Callaghan C.J.,Queens University | Hu N.,Queens University | Ding K.,Queens University | And 6 more authors.
British Journal of Cancer | Year: 2013

Background:The ACCENT database, with individual patient data for 20 898 patients from 18 colon cancer clinical trials, was used to support Food and Drug Administration (FDA) approval of 3-year disease-free survival as a surrogate for 5-year overall survival. We hypothesised substantive differences in survival estimation with log-normal modelling rather than standard Kaplan-Meier or Cox approaches.Methods:Time to relapse, disease-free survival, and overall survival were estimated using Kaplan-Meier, Cox, and log-normal approaches for male subjects aged 60-65 years, with stage III colon cancer, treated with 5-fluorouracil-based chemotherapy regimens (with 5FU), or with surgery alone (without 5FU).Results:Absolute differences between Cox and log-normal estimates with (without) 5FU varied by end point. The log-normal model had 5.8 (6.3)% higher estimated 3-year time to relapse than the Cox model; 4.8 (5.1)% higher 3-year disease-free survival; and 3.2 (2.2)% higher 5-year overall survival. Model checking indicated greater data support for the log-normal than the Cox model, with Cox and Kaplan-Meier estimates being more similar. All three model types indicate consistent evidence of treatment benefit on both 3-year disease-free survival and 5-year overall survival; patients allocated to 5FU had 5.0-6.7% higher 3-year disease-free survival and 5.3-6.8% higher 5-year overall survival.Conclusion:Substantive absolute differences between estimates of 3-year disease-free survival and 5-year overall survival with log-normal and Cox models were large enough to be clinically relevant, and warrant further consideration. © 2013 Cancer Research UK. Source


Wolff A.C.,Johns Hopkins Kimmel Comprehensive Cancer Center | Hammond M.E.H.,University of Utah | Hicks D.G.,University of Rochester | Dowsett M.,Royal Marsden Hospital | And 15 more authors.
Journal of Clinical Oncology | Year: 2013

Purpose: To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. Methods: ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. Results: The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. Recommendations: The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. Copyright © 2013 American Society of Clinical Oncology and College of American Pathologists. All rights reserved. Source


Wolff A.C.,Johns Hopkins Kimmel Comprehensive Cancer Center | Hammond M.E.H.,University of Utah | Hicks D.G.,University of Rochester | Dowsett M.,Royal Marsden Hospital | And 15 more authors.
Archives of Pathology and Laboratory Medicine | Year: 2014

Purpose. To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. Methods. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing. Results. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations. Recommendations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patientswith invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. Copyright © 2014 College of American Pathologists. Source


Vogel V.G.,National Surgical Adjuvant Breast and Bowel Project | Vogel V.G.,University of Pittsburgh | Costantino J.P.,National Surgical Adjuvant Breast and Bowel Project | Costantino J.P.,University of Pittsburgh | And 6 more authors.
Journal of the National Cancer Institute - Monographs | Year: 2010

Background: In the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (BCPT), the reduction in risk of noninvasive breast cancer was 50%. There were 93 cases in women receiving placebo and 60 in those receiving tamoxifen (P = .008). Through 7 years of follow-up, the cumulative incidence of noninvasive breast cancer among the placebo group was 15.8 per 1000 women vs 10.2 per 1000 women in the tamoxifen group. In the initial report of the Study of Tamoxifen and Raloxifene (STAR trial), the rate for noninvasive breast cancer was 1.51 per 1000 women assigned to tamoxifen and 2.11 per 1000 women assigned to raloxifene (risk ratio, 1.40; 95% confidence interval = 0.98 to 2.00). Methods: Additional follow-up of the NSABP STAR trial through March 31, 2009 is reported with a focus on noninvasive breast cancer events. Results: Through 81 months of median follow-up in the NSABP STAR trial, there are 137 cases of noninvasive breast cancer in the raloxifene group compared with 111 cases in the tamoxifen group (risk ratio = 1.02, 95% confidence interval = 0.61 to 1.70). The occurrence of ductal carcinoma in situ with raloxifene was seen more frequently among women with lower baseline Gail scores and no atypical hyperplasia than in women taking tamoxifen therapy. Raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive breast cancer. Conclusions: Although these data indicate that raloxifene offers less protection than tamoxifen for postmenopausal women who are at increased risk for both invasive and noninvasive breast cancer, the favorable risk-benefit profile for raloxifene affords acceptable clinical reduction in the risk of in situ cancers among postmenopausal women. © The Author 2010. Published by Oxford University Press. All rights reserved. Source


Sinicrope F.A.,Mayo Medical School | Foster N.R.,Mayo Medical School | Marsoni S.,SENDO Foundation | Monges G.,Institute Paoli Calmettes | And 6 more authors.
Journal of the National Cancer Institute | Year: 2011

Background Approximately 15% of colorectal cancers develop because of defective function of the DNA mismatch repair (MMR) system. We determined the association of MMR status with colon cancer recurrence and examined the impact of 5-fluorouracil (FU)-based adjuvant therapy on recurrence variables.MethodsWe included stage II and III colon carcinoma patients (n = 2141) who were treated in randomized trials of 5-FU-based adjuvant therapy. Tumors were analyzed for microsatellite instability by polymerase chain reaction and/or for MMR protein expression by immunohistochemistry to determine deficient MMR (dMMR) or proficient MMR (pMMR) status. Associations of MMR status and/or 5-FU-based treatment with clinicopathologic and recurrence covariates were determined using χ2 or Fisher Exact or Wilcoxon rank-sum tests. Time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were analyzed using univariate and multivariable Cox models, with the latter adjusted for covariates. Tumors showing dMMR were categorized by presumed germline vs sporadic origin and were assessed for their prognostic and predictive impact. All statistical tests were two-sided.ResultsIn this study population, dMMR was detected in 344 of 2141 (16.1%) tumors. Compared with pMMR tumors, dMMR was associated with reduced 5-year recurrence rates (33% vs 22%; P <. 001), delayed TTR (P <. 001), and fewer distant recurrences (22% vs 12%; P <. 001). In multivariable models, dMMR was independently associated with delayed TTR (hazard ratio = 0.72, 95% confidence interval = 0.56 to 0.91, P =. 005) and improved DFS (P =. 035) and OS (P =. 031). In stage III cancers, 5-FU-based treatment vs surgery alone or no 5-FU was associated with reduced distant recurrence for dMMR tumors (11% vs 29%; P =. 011) and reduced recurrence to all sites for pMMR tumors (P <. 001). The dMMR tumors with suspected germline mutations were associated with improved DFS after 5-FU-based treatment compared with sporadic tumors where no benefit was observed (P =. 006). ConclusionsPatients with dMMR colon cancers have reduced rates of tumor recurrence, delayed TTR, and improved survival rates, compared with pMMR colon cancers. Distant recurrences were reduced by 5-FU-based adjuvant treatment in dMMR stage III tumors, and a subset analysis suggested that any treatment benefit was restricted to suspected germline vs sporadic tumors. © 2011 The Author. Source

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