Study of Tissue Samples From Women Treated With Paclitaxel for Breast Cancer on Clinical Trial CALGB-9344 or CALGB-9741
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00991263|
Recruitment Status : Completed
First Posted : October 7, 2009
Last Update Posted : August 8, 2017
RATIONALE: Studying the genes expressed in samples of tumor tissue from patients with cancer may help doctors identify biomarkers related to cancer.
PURPOSE: This research study is looking at tissue samples from women treated with paclitaxel for breast cancer on clinical trial CALGB 9344 or CALGB 9741.
|Condition or disease||Intervention/treatment|
|Breast Cancer||Genetic: gene expression analysis Genetic: polymerase chain reaction Other: laboratory biomarker analysis|
Hide Detailed Description
- To determine whether subtype-specific treatment effects correlate with disease-free survival (DFS), as determined by a significant interaction between PAM50-based intrinsic subtypes, and (a) paclitaxel benefit in CLB-9344 and (b) dose density in CALGB-9741.
- To determine whether subtype-specific treatment effects correlate with DFS for the HER2-negative subsets in CALGB-9344 and CALGB-9741, as determined by analysis of tissue microarray (TMA) and slides.
- To determine the relationship between PAM50-defined risk of relapse (ROR) score and DFS in CALGB-9344 and CALGB-9741.
- To evaluate the relationship between PAM50-defined ROR score and DFS in the HER2-negative subsets in CALGB-9344 and CALGB-9741, as determined by analysis of TMA and slides.
- To examine the relationship between PAM50-defined proliferation score and DFS in CALGB-9344 and CALGB-9741 in multivariate Cox-proportional hazards models including the following covariates: (a) number of positive lymph nodes, square root transformation; (b) menopausal status (pre versus peri/post); CALGB-9344 only; c) dose of doxorubicin hydrochloride (60/75/90 mg/m^2); and CALGB-9741 only; and (d) sequence of treatment.
- To evaluate overall survival (OS) in a Cox-proportional hazards-regression model for testing the interaction between ROR with (a) paclitaxel benefit in CALGB-9344 and (b) dose density in CALGB-9741.
- To test for a significant interaction between ROR and paclitaxel benefit at 5-year and 10-year DFS.
- To test whether 5-year and 10-year DFS rates can be associated to a significant interaction between the proliferation score with (a) paclitaxel benefit in CALGB-9344 and (b) dose density in CALGB-9741.
OUTLINE: Tissue blocks from CALGB-9344 and CALGB-9741 are utilized to purify RNA to be tested in the PAM50 assay (a 50-gene quantitative PCR assay, that provides an intrinsic breast cancer subtype diagnosis) and generate risk of relapse (ROR) scores.
The assay identifies five subtypes with the following characteristics:
- Luminal A: This subtype expresses estrogen receptor (ER) accompanied by high levels of ER-associated gene expression. Genes associated with cell cycle activation are not highly expressed and this tumor type is only very rarely HER2+. This subgroup has the most favorable prognosis and is enriched for endocrine therapy responsive tumors.
- Luminal B: This subtype expresses ER and ER-associated gene expression but to a lower extent. Genes associated with cell cycle activation are highly expressed and this tumor type can be HER2+ (~20%) or HER2- thus, from the clinical perspective, Luminal B tumors are at least two further subtypes defined by the presence or absence of HER2-gene amplification. The prognosis is unfavorable (despite ER expression) and endocrine therapy responsiveness is generally diminished.
- Basal-like: This subtype is ER-, is almost always clinically HER2- and expresses a suite of "basal" biomarkers. Genes associated with cell cycle activation are highly expressed.
- HER2-enriched: This subtype is ER- and is HER2+ in the majority of cases. Genes associated with cell cycle activation are highly expressed and these tumors have a poor outcome. Tumors within this classification that are clinically HER2- fall into a class previously described as double-negative non-basal.
- Normal-like: A tumor subtype diagnosis cannot be provided from samples that exhibit a normal-like profile. Since this profile was trained on samples without cancer, "normal-like" implies there are too few tumor cells in the sample to make a true tumor subtype diagnosis.
PROJECTED ACCRUAL: A total of 2,245 tissue blocks from CALGB-9544 and 1,432 tissue blocks from CALGB-9741 will be accrued for this study.
|Study Type :||Observational|
|Estimated Enrollment :||3677 participants|
|Official Title:||Intrinsic Breast Cancer Subtypes and Benefit of Paclitaxel in CALGB 9344 and Dose Dense Therapy in CALGB 9741|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||May 2010|
|Actual Study Completion Date :||February 2012|
Tissue blocks from CALGB-9344 and CALGB-9741 are utilized to purify RNA to be tested in the PAM50 assay (a 50-gene quantitative PCR assay, that provides an intrinsic breast cancer subtype diagnosis) and generate risk of relapse (ROR) scores. For more information, see Details section.
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis
- Disease-free survival (DFS) [ Time Frame: Up to 10 years ]
- 5- and 10-year DFS rates [ Time Frame: Up to 10 years ]
- Overall survival [ Time Frame: Up to 10 years ]
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00991263
|Study Chair:||Matthew J. Ellis, MD, PhD, FRCP||Washington University Siteman Cancer Center|