MRI and Gene Expression in Diagnosing Patients With Ductal Breast Cancer In Situ

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with ductal carcinoma in situ (DCIS) diagnosed on
core needle biopsy judged to be breast conservation candidates based upon standard imaging
(mammography +/- sonography) and physical examination (a) who convert to mastectomy in step 1
based on MRI findings, and (b) who have a mastectomy as the final surgical procedure in step
2.

SECONDARY OBJECTIVES:

I. To assess the relation between baseline clinical covariates (e.g., tumor grade, necrosis,
histologic type, mammographic lesion size), MRI morphologic and kinetic features, and the
DCIS score.

II. To assess the diagnostic accuracy of MRI in extent of disease evaluation in patients with
DCIS.

III. To estimate the proportion of patients who require re-operation because of inadequate
excision after MRI.

IV. To estimate the proportion of patients who proceed to mastectomy after an initial attempt
at wide local excision because of either inadequate tumor-free margins (< 2 mm), or other
reasons.

V. To estimate the 5-year and 10-year ipsilateral breast event (in situ and invasive) rate
(IBE) among women with DCIS assessed with MRI preoperatively and treated with wide local
excision without radiation therapy (if there is a low DCIS score) or with radiation therapy
(if there is an intermediate-high DCIS score).

VI. To estimate the proportion of women with DCIS who receive treatment that is concordant
with their treatment goals and concerns.

VII. To estimate the proportion of women with DCIS whose decision autonomy preference was
concordant with perceived level of decision involvement.

VIII. To assess decision quality using knowledge score and decision process. IX. To assess
concordance between decision autonomy preference and perceived level of decision involvement,
knowledge and decision process scores as independent predictors of decision satisfaction at
the first post-operative visit.

X. To assess the relationship of patient-reported outcomes and disease-specific covariates,
and quality of life after treatment.

XI. To assess the role of disease status, diagnostic test results and surgeon recommendation
as predictors of treatment received.

XII. To compare the patient-reported diagnostic testing burden of bilateral mammography and
MRI as measured by Testing Morbidities Index (TMI).

OUTLINE:

STEP 1:

ARM A: Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or
biopsies if indicated based on MRI.

STEP 2: Patients are assigned to 1 of 2 treatment arms based on the results of the MRI.

ARM B: Patients undergo a mastectomy. Patients do not register for Step 3.

ARM C: Patients undergo wide local excision +/- re-excision. Patients may cross-over to Arm B
if mastectomy is indicated. Tissue samples collected during surgery are used to calculate the
DCIS score using genetic analysis testing. Patients may then proceed to Step 3.

STEP 3: Patients are assigned to 1 of 2 treatment arms based on the results of the DCIS score
test.

ARM D (DCIS score < 39): Patients undergo endocrine therapy as directed.

ARM E (DCIS score >= 39): Patients undergo radiation therapy and endocrine therapy as
directed.

After completion of study treatment, patients are followed up every 6 months for 5 years and
then every 12 months for 5 years.

Inclusion Criteria:

- Registration to Step 1:

- Patients must have pathologically confirmed diagnosis of unilateral ductal carcinoma
in situ with no evidence of microinvasive or invasive disease obtained by core needle
biopsy within 4 months of registration; patients diagnosed by surgical excision are
not eligible; patients with synchronous bilateral disease are not eligible; patients
with synchronous bilateral disease (i.e., synchronous DCIS or invasive cancer) are not
eligible

- Patients will be staged prior to registration according to the clinical staging
criteria adapted from the American Joint Committee on Cancer (AJCC) Cancer
Staging Data Forms of the AJCC Cancer Staging Manual, 7th Edition, 2009; Note:
For consistency purposes, AJCC 7th Edition will continue to be used throughout
the entire study enrollment period

- Required studies include a bilateral screening mammogram within 6 months and
diagnostic mammogram of the affected breast within 3 months prior to registration

- Patients must not have previous ipsilateral invasive breast cancer or DCIS

- Patients must not have known deleterious mutations in breast cancer (BRCA) genes

- Patients must not have received hormonal therapy (i.e., tamoxifen, raloxifene, and/or
aromatase inhibitors) for prevention of breast cancer within 3 months of the biopsy
documenting DCIS

- Patients must not have history of chemotherapy for cancer within 6 months prior to
registration

- No prior history of breast radiotherapy that will prevent the use of radiotherapy for
the present DCIS

- Patients must be judged to be 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
28 days prior to registration;

- Weight lower than that allowable by the MRI table;

- No prior MRI of the breasts within the 6 months prior to registration

- Patients must be eligible for breast-conserving therapy (BCT) based on clinical
examination and mammography; if ultrasound is performed, findings must also be
consistent with eligibility for BCT

- Patients must not have multicentric disease scheduled to undergo multiple
lumpectomies; multifocal disease that can be encompassed in a single operative bed are
eligible

- Women must not be pregnant or breast-feeding; all females of childbearing potential
must have a blood test or urine study within 3 weeks prior to registration to rule out
pregnancy; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential must be strongly advised to use an accepted and
effective method of contraception or to abstain from sexual intercourse for the
duration of their participation in the study

- Registration to Step 2:

- MRI has been performed in Step 1, and additional imaging studies and biopsies
performed if indicated

- The clinician/patient has made the decision as to whether the patient will proceed to
wide local excision or mastectomy

- Registration to Step 3:

- Patient's most recent surgery was wide local excision with or without re-excision and
for which there was obtained clear (>= 2 mm) margins at breast conserving surgery, and
the pathology reveals pure DCIS; patients with invasive cancer or DCIS with
microinvasion will not be registered on step 3, but will be followed for clinical
outcomes

- The OncotypeDX Patient Report of the DCIS Score from the OncotypeDX Breast Cancer
Assay performed by Genomic Health on the excision tissue have been uploaded by the
site into the Rave electronic case report forms (eCRF)