Genetic Testing in Predicting Tumor Response in Patients With Stage I-III HER2 Negative Invasive Breast Cancer

Feasibility, Validation and Implementation of Genomic Testing for Chemotherapy and Endocrine Sensitivity of HER2 Negative Primary Invasive Breast Cancer (Clinical Stage I to III)


Lead Sponsor: M.D. Anderson Cancer Center

Collaborator: National Cancer Institute (NCI)

Source M.D. Anderson Cancer Center
Brief Summary

This phase II trial studies how well genetic testing works in predicting tumor response in patients with stage I-III HER2 negative invasive breast cancer. Genetic testing is a procedure that tests tumor samples to learn if certain genes are activated (turned on) in the tumor and if the activation of these genes may predict if the tumor will be sensitive or resistant to routine breast cancer treatments, such as chemotherapy or hormonal therapy.

Detailed Description


I. To determine the feasibility of implementation of molecular (genomic) predictive testing for patients with localized (stage I-III) invasive carcinoma of the breast who are candidates for either adjuvant or neoadjuvant treatment of their breast cancer.


I. Estimate the frequency of tumors in each of the four molecularly defined cohorts, overall and within subsets defined by nodal status and estrogen receptor (ER) status.

II. Estimate the concordance of genomic analysis of gene expression levels for ER and HER2 from the microarray (published previously), compared with standard testing with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) to determine ER and HER2 status in these tumors.

III. Estimate the rates of indeterminate results and other variables of feasibility for tissue obtained by different procurement methods.

IV. Estimate the impact of adjuvant therapy as measured by disease free survival (DFS) at 3 and 5 years for the patients within each cohort who received a neoadjuvant or adjuvant treatment that is concordant with the application of the prediction result.

V. Estimate the impact of neoadjuvant therapy for patients within each cohort, as measured by pathologic response in the breast and regional lymph nodes (pathologic complete response rate [pCR] and residual cancer burden [RCB]).

VI. Estimate the predictive performance of other pre-validated and published genomic predictors of chemotherapy or endocrine therapy sensitivity by calculating those predictions from the microarray data that are produced or by using available results if the test was performed separately for clinical use.

VII. Determine molecular characteristics of residual disease by analyzing resected surgical specimens of residual disease in patients who have received neoadjuvant chemotherapy.

VIII. Determine molecular characteristics of recurrent or metastatic disease by analyzing tumor tissue obtained from diagnostic biopsies of a recurrent or metastatic tumor and comparing these samples to the primary tumor.


Patients undergo biopsy or surgery to obtain tumor sample for genetic testing. Patients are then assigned to 4 treatment cohorts as determined by genetic test results.

After completion of study, patients are followed up for 5 years.

Overall Status Active, not recruiting
Start Date May 31, 2011
Completion Date May 31, 2021
Primary Completion Date May 31, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Feasibility defined as the ability to classify patients into 1 of 4 cohorts Up to 5 years
Secondary Outcome
Measure Time Frame
Disease-free survival (DFS) Time between diagnostic tumor biopsy and the first failure event, assessed at 3 and 5 years
Frequency of tumors Up to 5 years
Concordance of genomic analysis with immunohistochemistry (IHC) Up to 5 years
Indeterminate Results Up to 5 years
Enrollment 1100

Intervention Type: Procedure

Intervention Name: Biopsy

Description: Undergo tumor biopsy

Arm Group Label: Diagnostic (biopsy, surgery, genetic testing)

Other Name: Bx

Intervention Type: Procedure

Intervention Name: Conventional Surgery

Description: Undergo surgery

Arm Group Label: Diagnostic (biopsy, surgery, genetic testing)

Intervention Type: Other

Intervention Name: Genetic Testing

Description: Undergo genetic testing

Arm Group Label: Diagnostic (biopsy, surgery, genetic testing)



Inclusion Criteria:

- The patient can undergo biopsy or surgery of a primary tumor site for suspected or proven invasive breast cancer of clinical stage I to III; stage IV patients will be allowed and included in the feasibility assessment, but will not be included in outcomes analysis for secondary objectives

- The clinical or radiologic primary tumor size is at least 1 cm diameter

Exclusion Criteria:

- The patient has proven HER2-positive breast cancer, defined as a pathology report of amplification of the gene or 3+ score for immunohistochemical staining

- The patient has received prior systemic therapy or radiation therapy for breast cancer

- The patient has a prior history of invasive or metastatic cancer within 5 years of diagnosis of breast cancer, excluding squamous cell or basal cell carcinoma of the skin

- The patient had prior excisional biopsy of the primary invasive breast cancer

- There is hematoma or biopsy site changes that obscure the primary tumor

- Patients deemed medically ineligible for any adjuvant or neoadjuvant therapy. Patients with ER-positive (+) tumors deemed medically eligible for hormonal therapy, but not chemotherapy will be considered eligible for this protocol. Patients with ER-negative (-) tumors who are not candidates for adjuvant anthracycline based chemotherapy will be considered ineligible for this protocol. Patients who undergo biopsy and are later found to be ineligible for adjuvant therapy will be assessed for the primary objective, but will be excluded from the secondary objectives

Gender: Female

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Stacy Moulder Principal Investigator M.D. Anderson Cancer Center
Facility: M D Anderson Cancer Center
Location Countries

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Diagnostic (biopsy, surgery, genetic testing)

Type: Experimental

Description: Patients undergo biopsy or surgery to obtain tumor sample for genetic testing. Patients are then assigned to 4 treatment cohorts as determined by genetic test results.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Diagnostic

Masking: Double (Participant, Care Provider)

Masking Description: Patients and treating physicians will not be told the results of the experimental tests.