Focal Breast Pain: Does a Normal Ultrasound Provide Reassurance?

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.