Understanding and Predicting Breast Cancer Events After Treatment

840 women aged ≥18 years old scheduled to receive Adj-C for Stage I-III breast cancer and a
comparison population of 160 women without cancer (1,000 total). Equal numbers of women will
be recruited aged < 52 vs. > 52. At baseline, innovative MRI measures of CV function (LV and
aorta); measurements of submaximal (6-minute walk) and, on half of the cohort, maximal (peak
VO2) exercise capacity; questionnaire data to assess fatigue and behavioral and psychosocial
risk factors; and biomarkers will be collected.

Measurements will be repeated at 3±1, 12±2 (after the completion of radiation) and 24±2
months after initiation of Adj-C. This study will assess the relevance of pre-existing
factors such as age, black/white race, hypertension, smoking (yes/no), diabetes, coronary
artery disease, menopause status, CV medications, and physical activity on the study
outcomes. Also, this study will assess dynamic change in modifiable CV risk factors
(including BMI, blood pressure, serum lipids, serum glucose, physical activity, psychosocial
factors, lifestyle behaviors), and the cancer treatment including chemotherapy, radiation
therapy, immunotherapy, and surgery.

Inclusion Criteria for Women with Stage I - III Breast Cancer:

- Stage I-III female breast cancer (including inflammatory and newly diagnosed recurrent
breast cancer)

- > 18 years old

- Scheduled to receive chemotherapy

- Able to hold breath for 10 seconds

- ECOG 0 -2

Exclusion Criteria for Women with Stage I-III Breast Cancer:

- Those with ferromagnetic cerebral aneurysm clips or other intracranial metal;
pacemakers, defibrillators, functioning neurostimulator devices or other implanted
non-compatible MRI devices

- If previously measured, known LVEF <50%

- Inability to exercise on a treadmill or stationary cycle

- Symptomatic claustrophobia

- Unable to provide informed consent

- Pregnant or breasting feeding. Due to unknown risks and potential harm from the MRI to
the unborn fetus a negative serum pregnancy test within 10 days prior to registration
is required in women with child-bearing potential. For this reason women of
child-bearing potential must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence (not having sex), oral contraceptives,
intrauterine device (IUD), DeProvera, tubal ligation, or vasectomy of the partner
(with confirmed negative sperm counts) in a monogamous relationship (same partner). An
acceptable, although less reliable method involves the careful use of condoms and
spermicidal foam or gel and/or cervical cap or sponge prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her study physician
immediately. The cardiac MRI should be delayed until after childbirth.

Inclusion Criteria for Women Free of Cancer for Comparison:

- Healthy female without known coronary artery disease > 18 years old

- ECOG = 0 or 1

- Able to exercise on a treadmill or stationary cycle

- BMI <35

- No hx. of cancer

- Never received chemotherapy, radiation therapy, immunotherapy, or had breast surgery
if previously measured, LVEF ≥ 50%

Exclusion Criteria for Women Free of Cancer for Comparison:

- Inflammatory conditions such as lupus or inflammatory bowel disease or chronic health
conditions consisting of, existing CV risk factors such as: Coronary artery disease or
heart failure.

- Other exclusions include those with ferromagnetic cerebral aneurysm clips or other
intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices or
other implanted non-compatible MRI devices

- Symptomatic claustrophobia

- Unable to provide informed consent

- Pregnant or breasting feeding. Due to unknown risks and potential harm from the MRI to
the unborn fetus a negative serum pregnancy test within 10 days prior to registration
is required in women with child-bearing potential. For this reason women of
child-bearing potential must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence (not having sex), oral contraceptives,
intrauterine device (IUD), DeProvera, tubal ligation, or vasectomy of the partner
(with confirmed negative sperm counts) in a monogamous relationship (same partner). An
acceptable, although less reliable method involves the careful use of condoms and
spermicidal foam or gel and/or cervical cap or sponge prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her study physician
immediately. The cardiac MRI should be delayed until after childbirth.