Clinical trial NCT00033397: Diagnostic Procedures in Women With Locally Advanced Breast Cancer Who Are Receiving Chemotherapy Before Breast Cancer Surgery
Official title: Contrast-Enhanced Breast MRI, MRS, And Correlative Science Studies To Characterize Tumor Response In Patients Undergoing Neoadjuvant Treatment For Locally Advanced Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE

Brief summary: RATIONALE: Comparing results of diagnostic procedures performed before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the most effective treatment.

PURPOSE: Diagnostic trial to study magnetic resonance imaging (MRI) and biomarkers in women who are receiving chemotherapy before surgery for locally advanced breast cancer.

Detailed description: OBJECTIVES:

Primary

* Support accrual to the ACRIN-6657/CALGB-150012 magnetic resonance imaging (MRI) correlative science study.
* Determine whether molecular markers, alone or in combination with MRI, at the time of diagnosis or early in the course of therapy, predict 3-year disease-free survival (DFS) in women with locally advanced breast cancer who are receiving neoadjuvant chemotherapy.
* Identify two groups of participants who have statistically different 3-year DFS, based on 1 or more biomarkers, including MRI.
* Determine whether biomarkers, in combination with MRI, early in the course of chemotherapy, improve the prediction of 3-year DFS and are at least as good of a predictor of DFS as residual disease at the time of surgery in these patients.
* Determine whether molecular markers are associated with specific imaging patterns seen on MRI of these patients.
* Predict response with MRI results and marker data from cell cycle check points, proliferation, angiogenesis, hormone receptors, and molecular profiles in these patients.

Secondary

* Determine the molecular predictors of lack of radiologic complete response (CR) in HER-2/neu negative patients (immunohistochemistry \[IHC\] score of 0, 1+, 2 and fluorescence in situ hybridization \[FISH\] not amplified) after a neoadjuvant anthracycline-based regimen.
* Determine the molecular predictors of lack of radiologic CR in HER-2/neu positive patients (IHC 3+ or FISH amplified \> 2.0) after a neoadjuvant anthracycline-based regime followed by a taxane alone regimen or in combination with trastuzumab.
* Determine the molecular predictors of complete magnetic resonance imaging radiologic response to a neoadjuvant anthracycline-based regimen when gene expression profiling is performed in a sequential, real-time fashion.

OUTLINE: This is a diagnostic, multicenter study conducted concurrently with CALGB-150012/ACRIN-6657 imaging protocol and concurrently with neoadjuvant anthracycline-based chemotherapy.

Patients receive an injection of gadopentetate dimeglumine and undergo magnetic resonance imaging (MRI) of the breast before initiation, 1-3 days after initiation, and then after completion of neoadjuvant anthracycline-based chemotherapy and prior to surgery. Patients who previously received a taxane also undergo an additional contrast-enhanced MRI scan.

Patients undergo biopsies before initiation and at the time of surgery. Patients also undergo blood draws at the time of the first biopsy and prior to surgery. Serum and tissue samples are used to assess biomarkers of genetic instability, cell cycle progression and cellular proliferation as predictors for anthracycline responsiveness, markers of apoptotic potential as predictors for taxane responsiveness in vivo, angiogenesis, hormone receptors, and molecular profiles using immunohistochemical methods.

Mammograms and possibly ultrasounds are performed prior to and after chemotherapy (before surgery).

Patients are followed every 6 months for 5 years and then annually for up to 10 years.

PROJECTED ACCRUAL: A total of 384 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed newly diagnosed adenocarcinoma of the breast by core needle biopsy, incisional biopsy, or fine needle aspiration (FNA)

  * Incisional biopsy must result in \< 10% removal of gross residual disease
* Measurable disease

  * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan OR
* Nonmeasurable disease
* Meets one of the following staging criteria:

  * Stage II or III disease
  * T4, any N, M0, including clinical or pathologic inflammatory disease
  * Regional stage IV disease where supraclavicular/infraclavicular lymph nodes are only site of metastasis
* No clinical or imaging evidence of distant metastasis
* Metaplastic carcinomas allowed
* Synchronous bilateral primaries allowed if the more advanced tumor meets staging criteria
* Patients for whom FNA was used to confirm initial diagnosis must have histologically confirmed invasive carcinoma by the start of chemotherapy
* Her-2/neu status known
* Currently receiving neoadjuvant chemotherapy consisting of a taxane-based regimen alone or followed by an anthracycline-based regimen
* Concurrent enrollment in the ACRIN-6657/CALGB-150012 imaging protocol required
* Hormone receptor status:

  * Any estrogen receptor or progesterone receptor status

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Female Cardiovascular
* No uncontrolled or severe cardiovascular disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* No ferromagnetic prostheses including the following:

  * Metallic implants not compatible with a magnetic resonance imaging machine
  * Heart valves
  * Aneurysm clips
  * Orthopedic prosthesis
  * Any metallic fragments anywhere in the body

PRIOR CONCURRENT THERAPY:

Chemotherapy

* See Disease Characteristics
* No prior chemotherapy to the ipsilateral breast for this malignancy

Endocrine therapy

* At least 4 weeks since prior tamoxifen or raloxifene

Radiotherapy

* No prior radiotherapy to the ipsilateral breast for this malignancy

Other

* No other prior cytotoxic regimens

Primary outcomes:
measure: response
timeFrame: Up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: University of California, San Francisco
name: Laura J. Esserman, MD, MBA
role: STUDY_CHAIR
References:
citation: Carey LA, Oh D, Sawyer L, et al.: Gene expression subtype and p53 mutational status are correlated among neoadjuvantly treated breast cancers in UNC LCCC9819 and I-SPY1 (CALGB 150007/ACRIN 6657). [Abstract] J Clin Oncol 24 (Suppl 18): A-10048, 552s, 2006.
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