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

Not Applicable

Active, not recruiting

• Conditions: Ductal Breast Carcinoma In Situ
• Interventions: Procedure: Magnetic Resonance Imaging; Procedure: Therapeutic Conventional Surgery; Procedure: Therapeutic Surgical Procedure; Drug: Endocrine Therapy; Radiation: Radiation Therapy; Other: Quality-of-Life Assessment; Other: Laboratory Biomarker Analysis; Other: Cytology Specimen Collection Procedure

• Registration Number: NCT02352883
• Lead Sponsor: ECOG-ACRIN Cancer Research Group

Brief Summary

This clinical trial studies magnetic resonance imaging (MRI) and gene expression in diagnosing patients with abnormal cells in the breast duct that have not spread outside the duct. MRI uses radio waves and a powerful magnet linked to a computer to create detailed pictures of areas inside the body. MRI may help find and diagnose patients with breast cancer. It may also help doctors predict a patient's response to treatment and help plan the best treatment. Genetic studies may help doctors predict the outcome of treatment and the risk for disease recurrence. Performing MRI with genetic studies may help determine the best treatment for patients with breast cancer in situ.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2015-01-16
• Study First Submitted QC: 2015-01-27
• Study First Posted: 2015-02-02
• Study Start: 2015-03-25
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-29
• Last Update Posted: 2024-07-03
• Primary Completion: 2027-11
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 368

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)

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm A (MRI)	Magnetic Resonance Imaging	Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or biopsies if indicated based on MRI.
Arm A (MRI)	Quality-of-Life Assessment	Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or biopsies if indicated based on MRI.
Arm A (MRI)	Laboratory Biomarker Analysis	Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or biopsies if indicated based on MRI.
Arm A (MRI)	Cytology Specimen Collection Procedure	Patients undergo MRI prior to surgery. Patients undergo additional imaging and/or biopsies if indicated based on MRI.
Arm B (mastectomy)	Therapeutic Conventional Surgery	Patients undergo a mastectomy. Patients do not register for Step 3.
Arm B (mastectomy)	Quality-of-Life Assessment	Patients undergo a mastectomy. Patients do not register for Step 3.
Arm B (mastectomy)	Laboratory Biomarker Analysis	Patients undergo a mastectomy. Patients do not register for Step 3.
Arm B (mastectomy)	Cytology Specimen Collection Procedure	Patients undergo a mastectomy. Patients do not register for Step 3.
Arm C (wide local excision)	Therapeutic Surgical Procedure	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.
Arm C (wide local excision)	Quality-of-Life Assessment	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.
Arm C (wide local excision)	Laboratory Biomarker Analysis	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.
Arm C (wide local excision)	Cytology Specimen Collection Procedure	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.
Arm D (endocrine therapy)	Endocrine Therapy	Patients undergo endocrine therapy as directed.
Arm D (endocrine therapy)	Quality-of-Life Assessment	Patients undergo endocrine therapy as directed.
Arm D (endocrine therapy)	Laboratory Biomarker Analysis	Patients undergo endocrine therapy as directed.
Arm D (endocrine therapy)	Cytology Specimen Collection Procedure	Patients undergo endocrine therapy as directed.
Arm E (radiation therapy, endocrine therapy)	Radiation Therapy	Patients undergo radiation therapy and endocrine therapy as directed.
Arm E (radiation therapy, endocrine therapy)	Endocrine Therapy	Patients undergo radiation therapy and endocrine therapy as directed.
Arm E (radiation therapy, endocrine therapy)	Quality-of-Life Assessment	Patients undergo radiation therapy and endocrine therapy as directed.
Arm E (radiation therapy, endocrine therapy)	Laboratory Biomarker Analysis	Patients undergo radiation therapy and endocrine therapy as directed.

Primary Outcome Measures

Name	Time	Method
Proportion of patients judged to be breast conservation candidates based upon standard imaging and physical examination who convert to mastectomy in step 1 based on MRI findings	After MRI (within 30 days following study entry), and prior to surgery
Proportion of patients judged to be breast conservation candidates based upon standard imaging and physical examination who have a mastectomy as the final surgical procedure in step 2	Up to 12 months post-op

Secondary Outcome Measures

Name	Time	Method
Factors associated with DCIS score	After surgery (DCIS Score is determined from surgical specimen)	The relation between baseline clinical covariates (tumor grade, necrosis, histologic type, mammographic lesion size), MRI morphologic and kinetic features, and the DCIS score will be assessed.
Proportion of patients who proceed to mastectomy after an initial attempt at wide local excision because of either inadequate tumor-free margins (< 2mm), or other reasons	Up to 12 months post-op	A two-sided 95% Wilson confidence interval will be derived. In addition to the overall probability of conversion in this cohort, estimates will be stratified by the reason for conversion.
IBE rate	At 10 years	Kaplan-Meier curves will be derived for the time to ipsilateral breast event for patients assigned to be treated with RT and those not treated with RT. Point estimates and 95% two-sided confidence intervals will be developed.
Diagnostic accuracy of MRI in extent of disease evaluation in patients with DCIS	Up to 12 months post-op
Proportion of patients who require re-operation because of inadequate excision after MRI	Up to 12 months post-op	A two-sided 95% Wilson confidence interval will be derived.
Proportion of women who receive treatment that is concordant with their treatment goals and concerns	Up to 24 months post-op	The proportion of patients with concordant care will be calculated and a 95% Wilson confidence interval will also be derived.
Decision quality, assessed using the composite of knowledge score and decision process score	Up to 5 days after pre-surgical consultation	To calculate knowledge score, a point for each correct answer on the knowledge questionnaire will be assigned, with missing responses receiving 0 points. A total score will be calculated for all patients who complete at least half of the items and scaled from 0-100%. To calculate a decision process score, a point will be assigned for each "yes" or "a lot/some" response. The sum will be scaled from 0-100%. The average of the two scores will be used as the outcome measure.
Patient-reported quality of life, measured using the Patient Reported Outcomes Measurement Information System (PROMIS)10 instrument	At 12 months post-op	The relationship of patient-reported outcomes and disease specific covariates, and quality of life will be assessed.
Role of disease status, diagnostic test results, and surgeon recommendation as predictors of treatment received	Up to 24 months post-op	Logistic regression modeling will be used in which the response variable will be the indicator of conversion to mastectomy (vs lumpectomy). The independent variables will include covariates describing disease status at baseline, MRI results, surgeon recommendation, patient decision involvement (such as the decision autonomy preference scale) and treatment concerns (as measured via the 7-item questionnaire). Separate analyses will be performed for conversion to mastectomy directly post MRI and conversion to mastectomy following BCS as the response variable.
Proportion of women whose decision autonomy preference was concordant with perceived level of decision involvement	Up to 5 days after pre-surgical consultation	Concordance will be defined as an exact match between decision autonomy preference (patient-based, shared, surgeon-based) and perceived level of decision involvement (patient based, shared, surgeon-based) as assessed by the Control Preferences Scale, reduced to three categories. The proportion of patients with concordance will be calculated for the sample. In addition, the degree of concordance over the group will be determined using kappa analysis.
Role of concordance between decision autonomy preference and perceived level of decision involvement, knowledge and decision process scores as independent predictors of decision satisfaction	Assessed via questionnaire administered at first post-operative visit	Linear regression modeling will be used in which the response variable will be decision satisfaction. The independent variables will be the indicator of concordance between decision autonomy preference and perceived level of decision involvement, the knowledge score and the decision process score. Two-way interactions between predictors will also be examined.
Patient-reported quality of life, measured using the PROMIS10 instrument	At 24 months post-op	The relationship of patient-reported outcomes and disease specific covariates, and quality of life will be assessed.
Patient-reported diagnostic testing burden of bilateral mammogram, MRI, and biopsies, measured by TMI	Up to 5 days after pre-surgical consultation	A Wilcoxon signed rank test will be used to compare TMI scores for mammography and MRI. In a secondary analysis regression modeling will be used to examine the effects of patient characteristics on the patient's perception of diagnostic test burden for the two modalities.

Trial Locations

Locations (76)

Waukesha Memorial Hospital; 🇺🇸 Waukesha, Wisconsin, United States

The Hospital of Central Connecticut; 🇺🇸 New Britain, Connecticut, United States

Kaiser Permanente-San Marcos; 🇺🇸 San Marcos, California, United States

Ingalls Memorial Hospital; 🇺🇸 Harvey, Illinois, United States

Helen F Graham Cancer Center; 🇺🇸 Newark, Delaware, United States

Greenwich Hospital; 🇺🇸 Greenwich, Connecticut, United States

Missouri Baptist Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Owensboro Health Mitchell Memorial Cancer Center; 🇺🇸 Owensboro, Kentucky, United States

Hope Women's Cancer Centers-Asheville; 🇺🇸 Asheville, North Carolina, United States

Montefiore Medical Center - Moses Campus; 🇺🇸 Bronx, New York, United States

Peninsula Regional Medical Center; 🇺🇸 Salisbury, Maryland, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

Kaiser Permanente-San Diego Zion; 🇺🇸 San Diego, California, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Abbott-Northwestern Hospital; 🇺🇸 Minneapolis, Minnesota, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

Easton Hospital; 🇺🇸 Easton, Pennsylvania, United States

Pottstown Memorial Medical Center; 🇺🇸 Pottstown, Pennsylvania, United States

Midstate Medical Center; 🇺🇸 Meriden, Connecticut, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Medical Oncology Hematology Consultants PA; 🇺🇸 Newark, Delaware, United States

Regional Hematology and Oncology PA; 🇺🇸 Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Edward Hospital/Cancer Center?Plainfield; 🇺🇸 Plainfield, Illinois, United States

John Fitzgerald Kennedy Medical Center; 🇺🇸 Atlantis, Florida, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Springfield Clinic; 🇺🇸 Springfield, Illinois, United States

Edward Hospital/Cancer Center; 🇺🇸 Naperville, Illinois, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

Memorial Regional Cancer Center Day Road; 🇺🇸 Mishawaka, Indiana, United States

IU Health West Hospital; 🇺🇸 Avon, Indiana, United States

Cancer Center of Kansas - Dodge City; 🇺🇸 Dodge City, Kansas, United States

Memorial Medical Center; 🇺🇸 Springfield, Illinois, United States

Cancer Center of Kansas - El Dorado; 🇺🇸 El Dorado, Kansas, United States

Lawrence Memorial Hospital; 🇺🇸 Lawrence, Kansas, United States

Cancer Center of Kansas - Salina; 🇺🇸 Salina, Kansas, United States

Cancer Center of Kansas - Wellington; 🇺🇸 Wellington, Kansas, United States

Cancer Center of Kansas-Wichita Medical Arts Tower; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas - Main Office; 🇺🇸 Wichita, Kansas, United States

Associates In Womens Health; 🇺🇸 Wichita, Kansas, United States

Mary Bird Perkins Cancer Center; 🇺🇸 Baton Rouge, Louisiana, United States

Louisiana Hematology Oncology Associates LLC; 🇺🇸 Baton Rouge, Louisiana, United States

Via Christi Regional Medical Center; 🇺🇸 Wichita, Kansas, United States

Cancer Center of Kansas - Winfield; 🇺🇸 Winfield, Kansas, United States

Medical Oncology LLC; 🇺🇸 Baton Rouge, Louisiana, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Hunterdon Medical Center; 🇺🇸 Flemington, New Jersey, United States

Robert Wood Johnson University Hospital Somerset; 🇺🇸 Somerville, New Jersey, United States

Virtua West Jersey Hospital Voorhees; 🇺🇸 Voorhees, New Jersey, United States

Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County; 🇺🇸 Mount Holly, New Jersey, United States

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States

Montefiore Medical Center-Einstein Campus; 🇺🇸 Bronx, New York, United States

Cancer Care of Western North Carolina; 🇺🇸 Asheville, North Carolina, United States

Mission Hospital-Memorial Campus; 🇺🇸 Asheville, North Carolina, United States

Aultman Health Foundation; 🇺🇸 Canton, Ohio, United States

Bryn Mawr Hospital; 🇺🇸 Bryn Mawr, Pennsylvania, United States

Adams Cancer Center; 🇺🇸 Gettysburg, Pennsylvania, United States

Penn State Milton S Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Riddle Memorial Hospital; 🇺🇸 Media, Pennsylvania, United States

Paoli Memorial Hospital; 🇺🇸 Paoli, Pennsylvania, United States

University of Pennsylvania/Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Lankenau Medical Center; 🇺🇸 Wynnewood, Pennsylvania, United States

Phoenixville Hospital; 🇺🇸 Phoenixville, Pennsylvania, United States

WellSpan Health-York Hospital; 🇺🇸 York, Pennsylvania, United States

Roger Williams Medical Center; 🇺🇸 Providence, Rhode Island, United States

Spartanburg Medical Center; 🇺🇸 Spartanburg, South Carolina, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States

Oconomowoc Memorial Hospital-ProHealth Care Inc; 🇺🇸 Oconomowoc, Wisconsin, United States

Aspirus Regional Cancer Center; 🇺🇸 Wausau, Wisconsin, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Ochsner Medical Center Jefferson; 🇺🇸 New Orleans, Louisiana, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States