A011104

Principal Investigator: Nicole  Winkler
Keywords: Breast MRI , Breast Cancer , Surgical Outcomes , Costs , Quality of Life Department: Radiology Clinical
IRB Number: 00099038 Co Investigator: Cindy Matsen
Specialty: Oncology
Sub Specialties: Breast Cancer
Recruitment Status: Recruiting

Contact Information

Nousheen Alasti
nousheen.alasti@hsc.utah.edu
801-585-6142

Brief Summary

Primary Objective

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

Secondary Objectives

1. 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.

2. To compare local recurrence rates between women who undergo BCT on the control arm to women who undergo BCT on the MRI arm.

3. 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 RT) between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI.

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

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

6. 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.

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

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

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

10. 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.

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

Correlative Science Objectives

Quality of Life

1. To compare patient reported QOL parameters between women randomized to the preoperative breast MRI arm and women randomized to the no pre-operative breast MRI arm.

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

3. To compare the QALY in patients randomized to the preoperative breast MRI arm versus those randomized to the no preoperative breast MRI arm.

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

Cost Effectiveness

1. 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.

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

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

Translational Studies

1. To determine molecular profile of chemonaive and chemoresistant breast cancer

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

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

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

Inclusion Criteria

Inclusion

  • A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:
    1. Female. Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.
    2. 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. For patients enrolled after receipt and completion of neoadjuvant chemotherapy, the clinical stage must be determined based on pre-chemotherapy assessment.
    3. Patients must have either:
    a. ER negative/PR negative (<10% by IHC staining) and HER-2 negative breast cancer.
    OR
    b. ER negative/PR negative (< 10% by IHC staining) and HER-2 positive tumors.
    c. HER2 status will be determined as per the 2013 ASCO CAP guidelines31:
    i. HER2 is considered positive if a) there is IHC 3+ staining or b) ISH positive using either single probe ISH or dual probe ISH
    ii. 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
    d. For patients enrolling after neoadjuvant therapy, the ER, PR, and HER2 markers are based on assessment prior to initiating neoadjuvant treatment.
    4. No patients with previous ipsilateral or contralateral invasive breast cancer or DCIS.
    5. No patients with bilateral breast cancer.
    6. No patients with known deleterious mutations in BRCA genes.
    7. No history of receiving endocrine therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures. These agents used previously as chemoprevention are allowed.
    8. Patients receiving neoadjuvant chemotherapy or recently completed neoadjuvant chemotherapy and will undergo surgery within 6 weeks are eligible.
    9. No patients scheduled to receive partial breast irradiation following breast conserving surgery.
    10. 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. For patients who have neoadjuvant therapy, eligibility for BCT is determined at completion of therapy. Repeat mammogram +/- US will be required at completion of neoadjuvant chemotherapy to determine eligibility for BCT.
    11. 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. For patients with multifocal or multicentric disease enrolled after completion of neoadjuvant chemotherapy, histologic confirmation of multifocality/multicentricity must have been completed before initiation of chemotherapy.
    12. Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):
    a. No history of untreatable claustrophobia;
  • b. 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);
    c. No history of sickle cell disease;
    d. No contraindication to intravenous contrast administration;
    e. 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 (see www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual.aspx for reaction definition and premedication guidance);
    f. No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 based on a creatinine level obtained within 28 days prior to registration;
    g. Weight lower than that allowable by the MRI table;
    13. No prior MRI of the study breast within the 12 months prior to registration.
    14. 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.
    15. ≥ 18 years of age.
    16. Signed study-specific informed consent prior to registration.

Exclusion Criteria

Exclusion

  • No patients with previous ipsilateral or contralateral invasive breast cancer or DCIS.
  • No patients with bilateral breast cancer.
  • No patients with known deleterious mutations in BRCA genes.
  • No 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 partial breast irradiation following breast conserving surgery.
  • 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. For patients with multifocal or multicentric disease enrolled after completion of neoadjuvant chemotherapy, histologic confirmation of multifocality/multicentricity must have been completed before initiation of chemotherapy.
  • No prior MRI of the study breast within the 12 months prior to registration.