Impact of Exercise on Mitigating the Cardio-toxic Effects of Adriamycin Among Women Newly Diagnosed With Breast Cancer.

This will be a pilot study that looks at the effect of exercise, while receiving
anthracycline therapy, on mitigating the cardio toxic effects of anthracyclines as assessed
by serial echocardiographic strain analysis.

Potential participants will be identified during chart review in advance of a routine clinic
visit or during a routine clinic visit with a provider. Individuals will be approached by the
provider or study team to determine willingness to learn more about a study for which they
may be eligible. Discussions regarding study participation will take place privately and
individuals will be provided with the Institutional Review Board (IRB) approved consent form.

In addition, potential participants may contact the study team directly. This contact may be
in the form of telephone, email, etc. Initial discussions regarding study participation may
take place by phone, email, etc., and individuals may be provided with the IRB approved
consent form and other IRB reviewed and approved materials (e.g., Patient Handout), as
applicable.

In all cases, as much time as is needed to consider study participation will be allowed to
possible participants; resulting in multiple phone calls, visits, emails, or other
communication, as necessary. For individuals who choose to take part, informed consent will
happen as per the consent process.

Patients will be recruited from the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center,
Sibley Memorial Hospital and the community. The investigators anticipate that among roughly
60 subjects approached for enrollment, 30 will be part of the final study. Participants who
agree to participate will be asked to provide written consent. Participants will be
randomized by an online system to one of the following two groups in a 1:2 ratio. Group
1(Usual care group) will receive a fitness tracker and flyers that reference the American
College of Cardiology/American Heart Association (ACC/AHA) guidelines for exercise and
physical activity for the general population. In addition to fitness tracker and flyers,
Group 2 (10,000 steps group) will receive additional messages and phone calls for motivation.
This group of participants will also be asked to take part in 30 minutes of continuous
exercise daily as part of their intervention.

For motivation, messages will be sent to study participants in group 2 via the messaging
center in the Under Armour application three times a week. With the application, study
participant will receive a phone alert and an email message to which they may respond if
needed. The frequency of messaging will be increased for participants who fail to meet their
goals for three consecutive days. In addition to the Under Armour application, participants
will be provided with a log sheet for recording their daily steps, whether 30 minutes of
continuous activity daily was completed and the type of the activity done for the 30 minutes.
Group two study subjects will also receive a weekly call to assess for side effects and
provide additional encouragement. Log sheets will be collected during oncology clinic visits
and the aforementioned intervention will be continued for the duration of their chemotherapy
treatment. Group 1 study participants will be assessed for side effects through a phone call
every 4 weeks.

For the study, women will be given an Under Armour band that will monitor daily steps, amount
of sleep and heart rate. Participants will be asked to download the Under Armour application
to their mobile phones so the data from their bands can be synced with the application daily.
For the intervention, study subjects will be asked to achieve a goal of 10,000 steps a day
and to engage in 30 minutes of continuous exercise every day and this can be any form of
exercise.

All patients who agree to participate will be invited to the Johns Hopkins Hospital medical
campus where all the testing will be performed. The investigators expect to complete the
study in 9 months.

Study participants who agree to participate will have the following assessments performed at
baseline:

1. A Cardiopulmonary Exercise Stress Test done using the standard protocol and supervised
by an exercise physiologist.

2. A 2D echocardiogram. The echocardiogram will include assessment of strain using speckle
tracking and tissue Doppler and the determination of systolic ejection time. All
patients routinely have an echocardiogram performed prior to the initiation of
cardio-toxic chemotherapy such as doxorubicin (Adriamycin), trastuzumab (Herceptin) and
pertuzumab (Perjeta), however, for the study, strain analysis will be performed off line
on the images obtained during the clinically indicated baseline echocardiogram.
Echocardiograms will be performed by experienced sonographers and on the same model echo
machine to reduce variability.

3. Bone densitometry assessment via a Dual-energy X-ray absorptiometry to measure total and
regional body composition in the frontal plane to determine bone, fat and fat-free mass.
The Dual-energy X-ray absorptiometry scan takes about 8-10 minutes. The total radiation
dose is approximately 1 millirem, which is very small.

4. Muscle strength will be measured using a hand grip tool.

5. Habitual activity levels will be assessed using the Rapid Assessment of Physical
Activity questionnaire, which categorizes activity levels on a scale from 1-7 (sedentary
to active).

6. Quality of life will be assessed with the Functional Assessment of Cancer Therapy-Breast
survey

7. Fatigue level will be performed with the Multidimensional Fatigue Symptom
Inventory-Short Form

8. All patients routinely have blood work collected, and as part of this research protocol,
the investigators will also collect blood to determine baseline tumor markers (
high-sensitivity C-reactive protein, Insulin-like growth factor 1, interleukin -6,
interleukin-1 and tumor necrosis factor alpha, leptin, adiponectin, estradiol, DNA
extraction, lymphocyte telomere length) and cardiac biomarkers (high sensitivity
troponin, troponin, pro-brain natriuretic peptide). The investigators will also collect
and store blood in order to keep open the possibility of doing a more extensive study to
look at any future genes that might be related to the phenotypes in this study (cancer,
cardiomyopathy, exercise response, etc.).

9. Cardiac history will be obtained at recruitment, including clinical risk factors for
heart disease (hypertension, diabetes and smoking history) and participants will be
evaluated throughout the study for any cardiac symptoms especially those of Heart
failure.

All of the above assessments will all be performed at baseline and repeated within 2 weeks of
the women completing their anthracycline-based chemotherapy. The investigators will also
track the clinical echocardiograms obtained at 12 months, but these results are not required
for the study.

Other studies: Serum troponin levels will be checked with each cycle of chemotherapy. Height
will be measured upon recruitment and weight and blood pressure will be measured at the time
of each echocardiogram.

Inclusion Criteria:

- Women who are 18 years and older

- Women newly diagnosed with stage I to III breast cancer who will be receiving adjuvant
or neoadjuvant doxorubicin-based chemotherapy

- Women who will be treated at the Johns Hopkins Hospital, Sibley Memorial Hospital or
who will be treated by oncologists in the community as long as we will have access to
treatment records.

- Women must be willing to receive follow up care either at Hopkins or with their local
oncologist for at least 1 year.

- Patients who are receiving therapy with an anthracycline.

- Women who have a smart phone

Exclusion Criteria:

- Inability to exercise

- Presence of metastatic disease

- Advanced pulmonary disease as assessed by clinical symptoms of shortness of breath or
known forced expiratory volume in 1 second < 1

- Any patients requiring oxygen at baseline

- The presence of known ischemic heart disease as defined by significant obstructive
heart disease (stenosis > 70%) seen on coronary angiography or cardiac CT

- Abnormal baseline cardiac function defined as an ejection fraction of less than 55%

- The presence of more than mild valvular stenosis or regurgitation, prosthetic valves
or pacemaker on their baseline echocardiogram

- Poor image quality on baseline echocardiogram or anatomic limitations that preclude
the acquisition of good quality images such as recent mastectomy or surgery

- Patients who do not have a smart phone onto which the Under Armour application can be
downloaded

- Patients who are unwilling to wear the Under Armour health band

- Pregnancy

- Previous anthracycline exposure

- Rhythms other than sinus rhythm

- Patients unwilling to come to the Johns Hopkins campus to have the required testing
performed