Focal Breast Pain: Does a Normal Ultrasound Provide Reassurance?
Focal Breast Pain: Does a Normal Ultrasound Provide Reassurance?
The investigator hypothesizes that a benign directed ultrasound, when performed after a
 normal digital mammogram, will provide women with focal breast pain additional reassurance
 that the etiology of their symptom is benign. 160 women over the age of thirty with focal
 breast pain who present to the Breast Imaging Clinic for evaluation between 3/1/2016 -
 7/1/2018 will be selected and randomized to three groups using a block randomization
 technique. All study participants will complete a survey assessing psychosocial factors, then
 receive a digital mammogram. Patients with a negative mammogram will continue on with the
 study and will either have a conversation about their negative mammogram with a radiologist
 or receive a directed ultrasound. A second survey will be conducted assessing psychosocial
 factors. All study participants who did not receive an ultrasound will receive an ultrasound
 so that all study participants are provided with the standard of care for focal breast pain.
 The results of the survey will be compared and appropriate statistical analyses such as an
 Analysis of Variance (ANOVA) test will be conducted to determine any statistically
 significant differences between the three randomized groups. The risks/safety issues of this
 study are believed to be minimal.
Protocol Title: Focal Breast Pain: Does a normal ultrasound provide reassurance?

 Purpose of the Study: The investigator hypothesizes that a benign directed ultrasound, when
 performed after a normal digital mammogram, will provide women with focal breast pain
 additional reassurance that the etiology of their symptom is benign.

 Background & Significance: Breast pain is one of the most common symptoms for which women
 seek medical care. While up to 80% of women experience breast pain at some point in their
 lives, most commonly breast pain results from a benign etiology such as trauma, infection,
 pregnancy, lactation, or simple cysts. In contrast, breast cancer is only reported in up to
 7% of women presenting with focal breast pain. Despite the uncommon association between
 breast cancer and focal breast pain, a diagnostic imaging workup is often requested. Current
 American College of Radiology (ACR) Appropriateness Criteria guidelines rate the use of
 mammography and ultrasound for the evaluation of non-cyclical, focal, unilateral or bilateral
 breast pain in patients 30 years and older as "may be appropriate." Traditionally both
 mammography and ultrasound are performed in women over the age of 30, who present with
 noncyclical, focal breast pain as imaging can often exclude a treatable benign cause of pain
 and/or provide reassurance.

 The investigator recently completed a retrospective study evaluating the utility of digital
 mammography and directed ultrasound in women with focal breast pain. It was observed that
 performing directed ultrasound following digital mammography was potentially beneficial in
 women with mammographically dense breast tissue. In contrast, the investigator demonstrated
 that directed ultrasound in conjunction with digital mammography was of low utility in women
 with non-dense breast tissue. These findings suggest that directed ultrasound might be
 unnecessary in the work up of focal breast pain for women with non-dense breast tissue.

 However, there is anecdotal evidence that a directed ultrasound yielding benign findings
 following a normal digital mammogram might further reassure women that the cause of focal
 breast pain is benign. These potential psychological benefits may drive the continued use of
 ultrasound in the work up of focal breast pain, even though their diagnostic utility is low.

 Design and Procedures:

 Subject Selection, Recruitment, and Compensation

 The study team (Principal investigator (PI), Co-PI, and Study coordinator) will select up to
 160 women, who present to the Breast Imaging Clinic for evaluation of focal breast pain
 between 3/1/2016 - 7/1/2018. Inclusion criteria include women over the age of 30 with primary
 focal breast pain, i.e. pain localizable by the patient to within one breast quadrant without
 other associated symptoms. Women with diffuse, radiating, or axillary pain, associated
 palpable findings at the site of pain, skin changes (erythema, thickening) or nipple changes
 (discharge, retraction), currently pregnant or breast-feeding, history of recent trauma or
 infection of the affected breast, and history of ipsilateral breast cancer will be excluded.

 Based on the investigator's clinical judgement, the investigator anticipates a minimum effect
 size of d=.4 for anxiety. A sample size of n =80 per group (total n = 160) has power of 0.8
 to detect differences with an effect size of d=.4 using a one-tailed alpha = .05.

 Study participants will include women referred for imaging because of focal breast pain and
 women who report focal breast pain to the technologist or radiologist prior to imaging. Once
 a patient is identified as a possible candidate, the PI, Co-PI, or study coordinator will
 look at electronic medical record, Epic. to see if they meet inclusion criteria and do not
 have any exclusion criteria. If there are none, the patient will be approached to see if they
 are willing to participate in the study. While the number of patients who present in a
 typical week to Duke with focal breast pain has not been studied, anecdotally, approximately
 1-2 patients per day have been evaluated for focal breast pain. Study participants will not
 be compensated.

 Consent Process

 Study participants will include women referred for imaging because of focal breast pain and
 women who report focal breast pain to the technologist or radiologist prior to imaging. Once
 a patient is identified as a possible candidate, the PI, Co-PI, or study coordinator will
 look at Epic to see if they meet inclusion criteria and do not have any exclusion criteria.
 If there are none, the patient will be approached to see if they are willing to participate
 in the study. Only a member of the study team (Karen Johnson, MD, Lars Grimm, MD, and Michael
 Cho, MD) will approach a potential participant for the consent process. If a member of the
 study team is not available, the potential subject will not be recruited. Subjects who are
 able to provide legally effective consent will be recruited.

 While the number of patients who present in a typical week to Duke with focal breast pain has
 not been studied, anecdotally, approximately 1-2 patients per day have been evaluated for
 focal breast pain.

 This study will serve as the 3/2 research project for Michael Cho, MD. Dr. Cho has requested
 37 weeks of dedicated research time during his 4th year to recruit patients. Dr. Cho will
 continue to recruit patients during his Breast imaging fellowship if needed. As such, Dr. Cho
 will be primarily responsible for the consent process. Dr. Cho will work with Steve Shipes to
 learn about the consent process and Maestro data entry.

 Study Design

 Once a patient volunteers to participate, the investigator will utilize a block randomization
 technique to randomize the study participants into two groups (Group A and B), ensuring
 comparable numbers across the study groups. The patient will then be consented. Pertinent
 demographic and medical data will also be collected.

 All included study participants will be asked to complete a short survey, based on the State
 Anxiety scale of the State-Trait Anxiety Inventory (STAI) (18). This survey will primarily
 assess psychosocial metrics, including, but not limited to anxiety, comfort, and level of
 concern for malignancy.

 All study participants will receive a digital mammogram, which is the standard of care for
 patients presenting with focal breast pain. Patients with no imaging correlate to the focal
 breast pain (Breast imaging-reporting and data system (BI-RADS) 1 and 2) will continue on
 with the study. Patients with an imaging finding at the site of focal pain (BI-RADS 0, 4, or
 5) will be excluded from the study and receive the standard care that is appropriate for the
 imaging finding.

 Women with BI-RADS 1 and 2 digital mammograms will proceed with the study and be informed of
 their imaging findings. Study participants randomized to Group A will receive their mammogram
 results from a Breast imaging fellow or fellowship trained Breast imaging radiologist.
 Participants in Group B will receive their mammogram results from a Breast imaging fellow or
 fellowship trained Breast imaging radiologist and additionally receive a directed ultrasound
 in the area of focal pain, which is the standard of care for focal breast pain.

 All study participants will be asked to complete a second survey, based on the State Anxiety
 scale of the State-Trait Anxiety Inventory.

 Participants in Groups A will receive a directed ultrasound of their breast at the end of the
 visit ensuring that all women receive the standard of care. One of the research collaborators
 will approach subjects in groups A following the 2nd survey to disclose the minor deception
 and explain to the subjects the necessity of the deception for the purposes of the study. The
 collaborator will also explain that the current standard of care for patients with focal
 breast pain is a targeted ultrasound. The standard of care ultrasound will then be performed
 by a Breast imaging fellow or fellowship trained breast radiologist.

 Risk/Benefit Assessment

 The risks of this study are believed to be minimal, including the potential loss of
 confidentiality. The digital mammogram and directed ultrasound patients will receive are the
 standard of practice for women with focal breast pain. Women in this study would have
 received these imaging tests regardless of their participation in the study and therefore the
 potential risks of imaging are not considered additional risks of this study.

 Costs to the Subject: There are no projected direct financial costs to the subjects involved
 in this study.

 Data Analysis & Statistical Considerations: The results of the survey will be compared and
 appropriate statistical analyses including but not limited to analysis of variance and
 multiple two sample t-tests conducted to determine any statistically significant differences
 between the three randomized groups.

 Data & Safety Monitoring: There are no anticipated safety concerns. The study coordinator
 (MC) will be responsible for the data collection and storage. Paper surveys will be stored in
 a locked cabinet in the Breast imaging reading room (Cancer Center Room 2S33) in the Cancer
 Center Breast Imaging Department (Clinic 2-1) which is accessible by badge only. Any digital
 data will be stored on an encrypted external hard drive (Western Digital) with a backup on
 Duke approved cloud storage (Box) and DTHS managed shared drive.

 Privacy, Data Storage & Confidentiality: A de-identification code will be assigned to the
 patients to be used as their identifier. The linking code identifying the subject will be
 kept for the duration of the study and will be securely stored on an encrypted external hard
 drive (Western Digital) with a backup on Duke approved cloud storage (Box) and DTHS managed
 shared drive.
Inclusion Criteria:

 -  women

 -  over the age of 30

 -  primary focal breast pain, i.e. pain localizable by the patient to within one breast
 quadrant without other associated symptoms.

 Exclusion Criteria:

 -  diffuse, radiating, or axillary pain

 -  associated palpable findings at the site of pain

 -  skin changes (erythema, thickening)

 -  nipple changes (discharge, retraction)

 -  currently pregnant or breast-feeding

 -  history of recent trauma or infection of the affected breast

 -  history of ipsilateral breast cancer will be excluded.