3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

PRIMARY OBJECTIVES:

I. To evaluate the rate of adverse cosmesis (defined as fair or poor cosmesis) with
accelerated 3 fraction APBI at 3 years, compared to baseline.

SECONDARY OBJECTIVES:

I. To evaluate the acute and late toxicities of accelerated 3 fraction APBI. II. To evaluate
local disease control of accelerated 3 fraction APBI. III. To assess the rate of patient
reported adverse cosmesis at 2 years, compared to baseline.

IV. To assess quality of life and other patient reported outcomes following accelerated 3
fraction APBI.

V. To compare the local control, acute and late toxicities, cosmesis, quality of life and
other patient reported outcomes between the three radiation therapy techniques (3D-CRT,
proton, brachytherapy).

VI. To evaluate clinical features, dose-volume parameters, and genetic variants associated
with fair and poor cosmetic outcome.

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT I: Patients undergo 3D-CRT APBI for 3-5 days.

COHORT II: Patients undergo proton beam radiation therapy APBI for 3-5 days.

COHORT III: Patients undergo brachytherapy ABPI for 3-5 days.

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

Inclusion Criteria:

- Grade 1-3 invasive ductal, mammary, mucinous, tubular, colloidal, or pure ductal
carcinoma in situ (DCIS) measuring =< 2.5 cm on final pathology (the tumor should be
clinical stage T1N0M0 in patients electing brachytherapy in whom the catheter will be
placed intraoperatively)

- Estrogen receptor (ER)+ (ER- DCIS meeting other eligibility criteria are eligible)

- Unicentric: patients with microscopic multifocality are eligible as long as the total
pathologic tumor size is =< 2.5 cm

- Surgical treatment of the breast must have been lumpectomy

- The final margins of the resected specimen must be histologically free of tumor

- Patients with DCIS do not require an axillary staging procedure; for patients with
invasive breast cancer (except T1mi), an axillary staging procedure should be
performed (either sentinel lymph node biopsy alone or axillary dissection and the
axillary node must be pathologically negative) and they should be pathologically node
negative; Note: Patients with N0 (i+) tumors on sentinel lymph node mapping or
dissection (i.e., if the tumor deposit is 0.2 mm or less as determined by
immunohistochemistry or hematoxylin and eosin staining) will also be eligible

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

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

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

- Ability to elect radiotherapy care in conjunction with their physician

- Able and willing to provide written informed consent

- Willingness 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 and collect involved blood
specimen prior to the start of radiation therapy, IRB number 15-000136.

Exclusion Criteria:

- Any of the following because this study involves therapy that has known genotoxic,
mutagenic and teratogenic effects:

- Pregnant women

- Nursing women

- Women of childbearing potential who are unwilling to employ adequate
contraception

- Neoadjuvant chemotherapy

- Prior history of ipsilateral breast cancer

- Prior radiation therapy to the ipsilateral breast or thorax

- 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

- Active collagen-vascular disease that, in the opinion of the treating physician, would
make this protocol unreasonably hazardous for the patient

- Paget?s disease of the breast

- Proven multicentric carcinoma (DCIS or invasive) in more than one quadrant or
separated by 4 or more centimeters or diffuse (> 1 quadrant) suspicious calcifications

- Histologic evidence of angiolymphatic invasion (ALI); Note: Cases termed focally
suspicious for ALI but where no definitive ALI is found are eligible

- Surgical margins that cannot be microscopically assessed or that are positive

- Pathologic tumor > 2.5 cm in size

- Metastatic disease

- Patients for whom the delivery of APBI is not feasible or any of the dosimetric
treatment criteria have not been met

- BRCA 1/2 mutation; Note: Patients are not required to undergo BRCA1 and BRCA2 or other
genetic mutation tests in order to enroll on the study. However, in the event a
patient is tested and is found to be a mutation carrier, she would be excluded from
the study

- Breast implants (patients who have had implants removed are eligible)

- Extensive intraductal component

- Active connective tissue disease

- Reduction mammoplasty if 3DCRT or proton APBI are planned

- Last surgery > 10 weeks from enrollment