Omission of Radiation in Patients With Her-2 Positive Breast Cancer

Participants, ages 50 and older diagnosed with stage I or stage II her-2 positive, node
negative breast cancer patients will be recommended to continue trastuzumab +/- pertuzumab
therapy after surgery to complete a full year of therapy as standard of care under the
clinical management of the patient's medical oncologist.

Once neoadjuvant chemotherapy has been completed, the patient will be separated in to one of
three arms based on a set of criteria for each. If the patient wishes to take part in the
study, but does not have a lumpectomy with sentinel lymph node biopsy showing pCR, the
patient will be placed in to Arm C and will proceed with radiation as standard of care. If
the patient wishes to take part in the study, and has a lumpectomy with sentinel lymph node
biopsy showing pCR, but does not agree to omission of radiation, the patient will be placed
in to Arm B and will proceed with radiation as standard of care. If the patient wishes to
take part in the study, and has a lumpectomy with sentinel lymph node biopsy showing pCR and
agrees to omission of radiation, the patient will be placed in to Arm A with follow up
assessments occuring at 1 month post-op, and every 3 months up to 5 years post-op.

Data will be collected on local, regional and distant recurrence at each follow-up.The
self-administered FACT-B+4 quality of life questionnaire will be given to patients at
baseline, at first postoperative visit, and at the one year post-operative visit.

Patients enrolling prior to chemotherapy will be asked to fill out the Breast-Q™ at the time
of their first surgical consultation. Patients enrolled post-surgery will be asked to fill
out the Breast-Q™ at their first post-operative visit. All patients will be asked to fill out
the Breast-Q™ at their yearly postoperative visits. The Breast-Q™ is a validated patient
assessment of breast cosmesis. This tool has both pre operative and post-operative
components. Pre-operative Breast-Q™ questionnaire data is not required of participants in
this study who enroll postoperatively.

Inclusion Criteria:

- Ability to understand and the willingness to sign a written informed consent.

- Karnofsky Performance Status 50% to 100% (Appendix A).

- Women 50 years of age or older with a diagnosis of invasive ductal carcinoma

- Her-2 3+ or FISH ratio of 2.2 or higher, background gene expression with normal copy
number

- Only postmenopausal women will be eligible. Subjects will be classified as being
postmenopausal if they have had:

- No spontaneous menses > 1 year, or

- Bilateral surgical oophorectomy, or

- No menses for < 1 year with FSH and estradiol levels in according to
institutional standards

- cT1-2N0 on clinical staging (verified to have no suspicious axillary or internal
mammary nodes on MRI or ultrasound)

- Undergo neoadjuvant chemotherapy with a trastuzumab based regimen prior to surgery and
plan for completion of one year of trastuzumab

- Patients are required to undergo lumpectomy with sentinel lymph node biopsy

- Pathologic review shows no evidence of residual disease in the tumor bed (to also
include no evidence of residual DCIS)

- Tumor bed should be no larger than 5 cm in size on pathologic review

- Fibrotic area of prior tumor located at least 3 mm away from surgical margins

- No evidence of treatment related change in the lymph nodes on pathologic review

Exclusion Criteria

- Diagnosis of inflammatory breast cancer

- Previously diagnosed malignancy excluding basal or squamous cell carcinoma of the skin
(unless disease-free for 5 years or more)

- Diagnosis of metastatic disease