Diagnostic Utility of MRI in Female Patients With Nipple Discharge: A Prospective Trial
Phase: NA
Conditions: Disorder of Nipple, Breast Neoplasms
Sponsor: Duke University

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Diagnostic Utility of MRI in Female Patients with Nipple Discharge: 
A Prospective Trial 
 
NCT02818946 
 
Document Date: June 20, 2016 
 

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Research Summary 
 
1. Protocol Title: 
Diagnostic Utility of MRI in Female Patients with Nipple Discharge: A Prospective 
Trial 
 
2. Purpose of the Study: 
The purpose of this prospective study is to determine the diagnostic value of MRI for 
the evaluation of patients with pathologic nipple discharge. 
 
3. Background & Significance: 
Nipple discharge, one of the most common reasons for referral to the breast imaging 
service, is often investigated by diagnostic mammography and sonography to 
evaluate for an underlying malignancy, the reported incidence of which ranges from 
3 to 29% (1-7).  If conventional imaging is negative, the patient may obtain further 
imaging with MRI, undergo ductography or ductoscopy, proceed to duct exploration 
and excision, or be observed (6, 8).  Findings on breast MRI, in addition to the 
patient’s symptomatology (frequency and volume of discharge) and risk of breast 
cancer, are used to inform the decision about whether to pursue surgery or watchful 
waiting (8). 
 
Limited research suggests that MRI may have a role in the evaluation of patients 
with nipple discharge because of its ability to identify mammographically- and 
sonographically-occult disease and to guide surgical excision (2, 9-16).  Previous 
research has drawn conclusions from small retrospective patient cohorts, and there 
is relatively wide variability in the reported diagnostic utility of MRI.  Consequently, 
duct exploration and excision remains the gold standard diagnostic approach (6, 8, 
17).  However, duct excision is an invasive procedure that can be technically 
challenging, especially if the affected duct cannot be localized or if the intraductal 
lesion is located far posteriorly in the breast, and can result in complications, such as 
interruption of the neurovascular supply to the nipple-areolar complex, cosmetic 
deformity, and breastfeeding limitations (18). 
 
Many women with nipple discharge and a negative conventional imaging workup 
undergo surgical excision, but few actually have underlying malignancy.  MRI may 
be useful to improve patient selection in this setting; in particular, a high negative 
predictive value of MRI may obviate the need for invasive surgery in patients who do 
not require intervention for symptomatic relief (8, 9, 17).  Our research group 
previously performed a retrospective study on this topic, which is currently under 
review for publication.  The negative predictive value of MRI was found to be 100%, 
but this study was significantly limited by selection bias; that is, only certain patients, 
at the discretion of the breast surgeon, underwent MRI as part of their workup. 
 
The purpose of the proposed prospective study is to determine the diagnostic value 
of MRI for the evaluation of patients with pathologic nipple discharge. 
 

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4. Design & Procedures: 
Referral for breast MRI in patients with pathological nipple discharge has changed in 
recent years.  Discussion with our breast surgeons indicate that referral for breast MRI 
has become routine for patients who present with pathological nipple discharge when in 
the past, referral was at the discretion of the breast surgeon.  For our study, patients 
with pathologic nipple discharge (unilateral and bloody or unilateral and clear) will be 
identified in either surgery clinic with presenting symptoms or in breast imaging clinic in 
one of 2 ways:  1) on the requisition under the “indication for exam” as specified by the 
referring clinician, or 2) by the technologist who asks routine questions to the patient.  
These patients will undergo conventional imaging with mammography and breast 
sonography first. If conventional imaging is negative or non-diagnostic, the patient will 
be seen in surgical clinic (Clinic 2-2 next door to ours) and contrast-enhanced breast 
MRI will be ordered by the surgeon as part of clinical care.  All patients will see a breast 
surgeon first before being approached for the study.  Once a patient is identified as 
having a planned contrast MRI, they will be approached by a CRC or resident/fellow 
participating in the study.  Our experience, based on a prior retrospective nipple 
discharge study, has shown that approximately 100 patients per year are encountered 
at our breast imaging clinic for evaluation of nipple discharge.  We expect that 
approximately 75% will agree to participate in the study.  This will yield a recruitment 
rate of 75 patients per year, hence the number specified in the study proposal.  Bracco 
Diagnostics will provide seed funding for 2 years for an anticipated total of 150 patients.   
 
We will only be obtaining data prospectively on patients who receive MRI's for clinical 
purposes (symptoms of pathological nipple discharge). When the clinical team notifies 
us that an MRI has been ordered for that purpose, we will consent the patients to 
document the results and follow-up. We will not be obtaining any MRI's on patient's for 
research purposes only. For that reason, we will be following clinical guidelines for 
obtaining creatinine, pregnancy tests, etc. 
 
The following data will be collected and analyzed: patient age, characteristics of the 
discharge (laterality, spontaneous versus expressed, duration of time, color, 
presence of blood), imaging workup and findings, BI-RADS final assessment 
categories, pathology results from core biopsy and/or surgical excision, and clinical 
and radiologic follow-up data during the two years after presentation.  
 
5. Selection of Subjects: 
See above detailed paragraph 
 
Inclusion criteria: female patients with unilateral and bloody nipple discharge OR 
unilateral and clear nipple discharge; clinical decision to have contrast enhanced 
MRI. 
Exclusion criteria: male gender, non-English speakers, age < 21 years, lack of 
capacity to give legally effective consent 
 
Note: It is highly unusual for lactating patients to present with pathologic discharge 
and therefore will likely not be identified for the study.  There is a very small potential 

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risk associated with absorption of contrast medium into the breast milk, but there is 
insufficient evidence to exclude women who are currently lactating from the study. 
 
Note: The costs of MRI will be covered by insurance.  In the unlikely event that a 
patient’s insurance denies coverage, the patient will be excluded from the study. 
 
6. Subject Recruitment & Compensation: 
The patient will be seen in surgical clinic (Clinic 2-2 next door to ours) and contrast-
enhanced breast MRI will be ordered by the surgeon. Potential subjects will be 
contacted and introduced to the study by the designated Clinical Research 
Coordinator or resident/fellow participating in the project. 
 
Recruitment will begin after approval of IRB and conclude after recruitment of 
approximately 150 subjects.  No financial compensation to subjects will be provided. 
 
7. Consent Process: 
Please see Section 14 of the e-IRB submission form. 
 
 
8. Subject’s Capacity to Give Legally Effective Consent: 
Subjects who do not have the capacity to give legally effective consent will not be 
included in this study. 
 
9. Study Interventions: 
Patients who choose to participate in our trial will have undergone mammography, 
breast sonography, and will be planning to have a contrast-enhanced breast MRI for 
evaluation of nipple discharge.  The study interventions are collection of clinical data 
for research purposes. 
 
 
 
10. Risk/Benefit Assessment: 
Participation in this study poses minimal risk to patients.  Risks to the subjects 
include loss of confidentiality.   
 
Loss of confidentiality is unlikely because the study data will be stored in the PI’s 
office and a shared drive. 
There will not be any direct benefit to the subjects; however, this research may help 
improve the diagnostic workup of nipple discharge in future patients. 
 
11. Costs to the Subject: 
There is no cost to the subject as a result of this study.  The costs of the MRI will be 
covered by insurance.  No financial compensation will be provided.   
 
12. Data Analysis & Statistical Considerations: 

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As discussed above, a high negative predictive value of MRI may obviate the need 
for invasive surgery in patients who do not require intervention for symptomatic 
relief.  Based on a statistical consultation with Dr. Kingshuk Roy Choudhary, we can 
achieve a negative predictive value of MRI of 95% with a margin of error of +/- 4.3%, 
if we recruit 100 subjects.  Our goal is to recruit approximately 150 subjects, with the 
expectation that some patients will not receive adequate two-year follow-up.   
 
The following data will be collected and analyzed: patient age, characteristics of the 
discharge (laterality, spontaneous versus expressed, duration of time, color, 
presence of blood), imaging workup and findings, BI-RADS final assessment 
categories, pathology results from core biopsy and/or surgical excision, and clinical 
and radiologic follow-up data during the two years after presentation.  
 
The sensitivity, specificity, positive predictive value (PPV), and negative predictive 
value (NPV) for MRI for the detection of malignancy will be calculated using 
standard formulas.  MRIs classified as BI-RADS categories 4 and 5 will be 
considered “positive,” while those classified as BI-RADS categories 1, 2, and 3 will 
be considered “negative.”  For purposes of the analysis, MRI will be considered to 
be “false positive” imaging if the biopsied and/or excised lesion does not reveal 
malignancy.  MRI will be considered “false negative” imaging if there is no 
suspicious finding on imaging (BI-RADS 1, 2, or 3) but subsequent pathology 
reveals malignancy. 
 
13. Data & Safety Monitoring: 
Consent forms will be stored in the PI’s office.  Patient names and medical record 
numbers will be recorded in a database on a shared drive only accessible by study 
researchers.  Once data collection is completed, these identifiers will be discarded.  
Only basic demographic information (age) will be retained. 
 
 
14. Privacy, Data Storage & Confidentiality: 
Please see Section 12 of the e-IRB submission form. 
 
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