Study of Tissue Samples From Women Treated With Paclitaxel for Breast Cancer on Clinical Trial CALGB-9344 or CALGB-9741

Breast Cancer Clinical Trial

Official title:

Intrinsic Breast Cancer Subtypes and Benefit of Paclitaxel in CALGB 9344 and Dose Dense Therapy in CALGB 9741

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00991263
• Other study ID #: CALGB-159905C-ICSC
• Secondary ID: CALGB-159905C-IC
• Status: Completed
• Phase: N/A
• First received: October 6, 2009
• Last updated: August 7, 2017
• Start date: April 2009
• Est. completion date: February 2012

Study information

• Verified date: August 2017
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3677
• Est. completion date: February 2012
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of stage II or IIIA breast cancer

• Received treatment with paclitaxel on clinical trial CALGB-9344 or CALGB-9741

• Tissue blocks available

PATIENT CHARACTERISTICS:

• See Disease Characteristics

• Pre-, peri-, or postmenopausal

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Genetic:
• gene expression analysis

• polymerase chain reaction

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)		Up to 10 years
Secondary	5- and 10-year DFS rates		Up to 10 years
Secondary	Overall survival		Up to 10 years