Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

MRI and Mammography before Surgery in Patients with Stage I-II Breast Cancer

Protocol: ALLIANCE-A011104

Full Title

Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women with Breast Cancer

Purpose

This randomized phase III trial studies how well magnetic resonance imaging (MRI) and mammography to work compared to mammography alone in patients with stage I-II breast cancer. Diagnostic procedures, such as MRI and mammography, may help in planning cancer treatment.

Study Objective

PRIMARY OBJECTIVES:

I. To compare the rates of local-regional recurrence (LRR) following attempted breast conserving therapy in a cohort of women with triple negative or human epidermal growth factor 2 (HER-2) amplified breast cancer randomized to preoperative staging with mammography (control arm) or mammography plus breast MRI (MRI arm).

SECONDARY OBJECTIVES:

I. To compare the re-operation rates following attempted breast conserving therapy between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI.

II. To compare local recurrence rates between women who undergo breast-conserving therapy (BCT) on the control arm to women who undergo BCT on the MRI arm.

III. To compare the conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis within the first 6 months of attempting BCT (prior to the administration of radiation therapy [RT]) between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI.

IV. To compare the contralateral breast cancer rates in women randomized to preoperative breast MRI to those not receiving pre-operative breast MRI.

V. To compare the disease-free survival rates between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI.

VI. To compare breast cancer specific and overall survival outcomes of women assessed preoperatively with breast MRI to those assessed without the use of breast MRI.

VII. To estimate the rate of MRI-guided localization assisted surgery.

VIII. To estimate the rate of multi-centric disease in the index breast for women in the MRI arm.

IX. To evaluate the accuracy of index lesion characteristics and other factors in predicting multi-centricity in the cohort randomized to breast MRI.

X. To assess the positive predictive values (PPV) of MRI in detecting ipsilateral multi-centric disease and contralateral disease in women with breast cancer undergoing preoperative breast MRI.

XI. To estimate the false positive rate for detection of multiple foci of breast cancer by MRI.

TERTIARY OBJECTIVES:

I. To compare patient reported quality of life (QOL) parameters between women randomized to the preoperative breast MRI arm and women randomized to the no pre-operative breast MRI arm.

II. To explore the impact that preoperative MRI has on patient QOL.

III. To compare the quality adjusted life years (QALY) in patients randomized to the preoperative breast MRI arm versus those randomized to the no preoperative breast MRI arm.

IV. To contribute to a bank of normative data of QOL outcomes in cancer patients.

V. To compare the estimated mean costs of breast cancer treatment between women randomized to the pre-operative breast MRI arm and women randomized to the no pre-operative breast MRI arm.

VI. To determine the incremental cost-effectiveness ratio of pre-operative breast MRI.

VII. To determine the impact of preoperative breast MRI using a net-benefit regression framework.

VIII. To determine whether clinical-pathologic variables predict LRR.

IX. To determine molecular characteristics that correlate with LRR and disease-free survival.

X. To determine molecular alterations that develops between primary tumors and recurrent tumors.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo mammography and breast conserving surgery.

ARM B: Patients undergo mammography, MRI, and breast conserving surgery.

After completion of study, patients are followed up every 4 months for 2 years and then every 6 months for 3 years.

Are you eligible?

Inclusion Criteria:

Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0); diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded

Patients must have either:

Estrogen receptor (ER) negative/progesterone receptor (PR) negative (< 10% by immunohistochemistry [IHC] staining) and HER-2 negative breast cancer OR

ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors

HER2 status will be determined per the 2013 American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines:

  • HER2 is considered positive if a) there is IHC 3+ staining or b) positive using either single probe in situ hybridization (ISH) or dual probe ISH
  • HER2 is considered negative if a) there is IHC 0 or 1+ staining or b) ISH negative using either single probe ISH or dual probe ISH

No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)

No patients with bilateral breast cancer

No patients with known deleterious mutations in breast cancer (BRCA) genes

No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures

No history of chemotherapy for cancer within 6 months prior to registration

No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery

Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram; women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial

No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies; multifocal disease that can be encompassed in a single operative bed can be enrolled

Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):

No history of untreatable claustrophobia

No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)

No history of sickle cell disease

No contraindication to intravenous contrast administration

No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance

No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) < 30

mL/min/1.73 m^2 based on a serum creatinine level obtained within 7 days prior to registration

Weight lower than that allowable by the MRI table

No prior MRI of study breast within the 12 months prior to registration

Non-pregnant and non-lactating; patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration; perimenopausal patients must be amenorrheic > 12 months to be considered not of child-bearing potential

Signed study-specific informed consent prior to registration

Breast Cancer