Trial Information

The PAL Trial (Physical Activity and Lymphedema)

The proposed study will recruit 288 healthy breast cancer survivors (1-15 years post
diagnosis, currently free of cancer), in two strata: 144 BrCa survivors with stable
lymphedema (defined in section D.2.), and 144 without lymphedema. The women with lymphedema
will be 1-15 years post diagnosis. The women without lymphedema will be 1-5 years post
diagnosis. The difference in timing is due to the timing of the onset of lymphedema.
Because 90% of all lymphedema cases are likely to occur by 5 years post treatment, it would
be of greater value to evaluate the safety of strength training for women without lymphedema
during the time frame when lymphedema is most likely to develop.

Randomization will be balanced by timing since diagnosis and other factors. Participants
will be randomly assigned within lymphedema strata, to the exercise intervention group or
the control group. Participants will be recruited in groups (a total of 8 waves) and
randomized to either a strength-training group or control group. All outcome measurements
will occur at baseline and 12 months later; additionally, all participants will undergo arm
volumetry circumference measures, and a subset of arm function tests (range of motion, pain,
grip strength) every 3 months.

Protection and safety of all participants All participants will be given access to trained
lymphedema specialists throughout study participation, paid for by the study, for evaluation
and treatment of lymphedema. Participants without lymphedema will all participate in an
educational session led by Dr. Schmitz and co-developed by Ms. Benson and Ms. Oatman to
ensure all participants enter the study with a clear understanding of lymphedema.

Each participant with lymphedema will undergo a clinical evaluation to review lymphedema
related measures and to assess current management strategies as part of the baseline and
12-month measurement visits. The protocol to standardize the content of these evaluation
sessions will be developed in the first twelve months of the study. Participants with
lymphedema, who wear a compression garment, will receive two free garments as part of
participating in the study. Arm volumes, circumferences, extra-cellular water in the arm
and a subset of arm function tests (range of motion, pain, grip strength) will be monitored
quarterly in all participants and monthly in treatment group participants. All participants
will be encouraged to request more frequent arm volumetry and/or circumferences and/or
extra-cellular water in the arm measures if they believe they have had or are concerned
about a change of symptoms. Any participant, regardless of group assignment, who
experiences the onset or a flare-up of lymphedema will be seen by a trained lymphedema
specialist for evaluation and treatment, paid for by the study. Clinical experiences of Ms.
Oatman and Ms. Benson suggest that 10% of the participants with lymphedema will experience a
flare-up over 12 months of participation.

For purposes of this study, a flare-up will be defined as a 5% increase in inter-limb
discrepancy in volume or circumference at the point of greatest visible difference.as
persistent pain/achiness/fullness (in the trunk and/or arm), persistent puffiness (visible),
or change of color that does not resolve within three days of rest, and that requires 5 or
more days of combined decongestive therapy to resolve. Further, for the purposes of this
study, onset of lymphedema will be defined as follows: among women not diagnosed with
lymphedema prior to study entry, a > 10% inter-limb discrepancy in volume or circumference a
the point of greatest visible difference OR swelling or obscuration of anatomic architecture
on close inspection OR pitting edema. as a 2 cm or 200 ml or greater difference between the
arm treated for breast cancer compared to the unaffected arm in a woman not diagnosed with
lymphedema prior to study entry. By these actions and the careful training of the fitness
trainers, we will monitor all participants carefully with regard to onset or worsening of
lymphedema symptoms.

The intervention group will receive social, behavioral support and research staff contact
time to encourage them to increase their activity level to include two weekly
strength-training sessions over 12 months. For the first three months, the exercise
sessions will be supervised and conducted in small groups of 4, to teach the specifics of
the protocol. Thereafter, participants will continue the same exercise protocol on their
own or in groups of their choosing. Treatment group participants will be held accountable
for completing workouts through exercise logs and reminder calls from research staff.
Participants in the treatment group will undergo assessments of arm volumes and
circumferences , as well as a subset of arm function tests (range of motion, pain, grip
strength) monthly.

The control group will undergo all outcome measures at baseline and 12 months, and a few
measures at 3 and 6 months. The outcome measures include assessments of arm circumferences,
extra-cellular water in the arm, and volumetry, as well as a subset of arm function tests
(range of motion, pain, grip strength), and will be asked to neither make purposeful changes
in diet nor to begin strength training until the final measures are completed 12 months
later. After completion of the final measures, control group participants will have the
option to participate in the same intervention offered to treatment group participants,
including a 1-year membership to the YMCA, Sisters in Shape gym, or Pottruck Health and
Fitness Center.