Proton Beam Radiation Therapy in Treating Patients With Breast Cancer After Surgery

PRIMARY OBJECTIVES:

I. To determine whether the 24 month complication rate (defined as grade 3 or greater late
adverse events; and unplanned surgical intervention in patients who undergo mastectomy with
reconstruction) of 15 fraction chest wall and regional node pencil beam scanning proton
radiotherapy is acceptable relative to 25 fraction chest wall and regional nodal pencil beam
scanning proton radiotherapy and worthy of further investigation.

SECONDARY OBJECTIVES:

I. To evaluate acute and late toxicity. II. To evaluate the rate of reconstruction failure
(defined as loss of the tissue expander or implant with the inability to replace it resulting
in no final reconstruction or conversion to autologous reconstruction or unplanned revision
with the addition of autologous reconstruction).

III. To determine the 5-year locoregional control, disease free survival and overall
survival.

IV. To evaluate fatigue, arm function, and other patient reported outcomes. V. To evaluate
clinical features, treatment technique, dose-volume parameters, histologic and genetic
variants associated with fair and poor cosmetic outcome or unplanned surgical intervention.

VI. To compare echocardiographic changes, including left ventricular strain pattern, between
fractionation regimens.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Within 12 weeks of the last breast cancer surgery or the last dose of adjuvant
chemotherapy and no sooner than 14 days since the last chemotherapy, patients receive
conventionally fractionated proton beam radiation therapy daily for 25 fractions.

ARM II: Within 12 weeks of the last breast cancer surgery or the last dose of adjuvant
chemotherapy and no sooner than 14 days since the last chemotherapy, patients receive
hypofractionated proton beam radiation therapy daily for 15 fractions.

After completion of study treatment, patients are followed up at 12 weeks, at 12, 24, and 36
months, and at 5 years.

Inclusion Criteria:

- Histologic confirmation of breast cancer resected by mastectomy with or without
immediate reconstruction and chest wall and regional nodal irradiation planned

- pStage T1-T4N0-N3M0 or ypStage T0-4N0-N3M0

- Note: The axilla must be staged by sentinel node biopsy alone, sentinel node
biopsy followed by axillary node dissection, or axillary lymph node dissection
alone

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

- Radiotherapy must begin within 12 weeks of last surgery (breast or axilla) or last
chemotherapy

- Note: Breast implants and expanders allowed

- Able to and provides Institutional Review Board (IRB) approved study specific written
informed consent

- Ability to complete questionnaire (s) by themselves or with assistance

- Able to complete all mandatory tests

- Willing to return to enrolling institution for follow-up (during the active monitoring
phase of the study)

- Willing to provide tissue and blood samples for correlative research purposes

- Rochester and Arizona patients: Willing to sign consent onto the Mayo Clinic
Radiotherapy Patient Outcomes Registry and Biobanking study, IRB number 15-000136

- Rochester patients: Willing to sign consent onto Evaluation of cardiac function in
patients undergoing proton beam or photon radiotherapy, IRB number 15-007443

Exclusion Criteria:

- Medical contraindication to receipt of radiotherapy

- Severe active co-morbid systemic illnesses or other severe concurrent disease which,
in the judgment of the investigator, would make the patient inappropriate for entry
into this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements or providing informed consent

- Active systemic lupus or scleroderma

- Pregnancy or women of childbearing potential who are sexually active and not
willing/able to use medically acceptable forms of contraception

- Prior receipt of ipsilateral breast or chest wall radiation that would result in
significant overlap of radiation therapy fields; prior contralateral radiotherapy for
breast cancer is allowed

- Positive margins after definitive surgery

- History of non-breast malignancies (except for in situ cancers treated only by local
excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior
study entry

- Inflammatory breast cancer

- Recurrent breast cancer

- Boosts to the chest wall after mastectomy; nodal boosts are allowed