Pertuzumab and Trastuzumab as Neoadjuvant Treatment in Patients With HER2-Positive Breast Cancer

This study will evaluate for the first time the correlation between early changes in SUV and
pCR in men and women with ER-negative, HER2-positive breast cancer receiving trastuzumab and
pertuzumab (PT) pre-operatively. This has not previously been evaluated in patients receiving
antiHER2 therapy alone and as such is novel and potentially practice changing. The results
from this phase 2 biomarker study will be used to plan a randomized study using a predefined
cut point for SUV decline such that the investigators can further attempt to identify a group
of individuals with HER2-positive early breast cancer who do not require cytotoxic
chemotherapy in addition to anti-HER2 agents. This non-invasive biomarker approach will be of
great interest to breast cancer oncologists and patients by facilitating a personalized
approach to managing patients with HER2-positive disease that will undoubtedly spare toxicity
and reduce the costs associated with anti-cancer strategies, without compromising efficacy.

Inclusion Criteria:

- Female and male patients, 18 years old or older

- Histologically proven infiltrating carcinoma of the breast on core needle biopsy that
is: ER/PR ≤10% staining by IHC and HER2 positive - IHC 3+, ISH ≥2.0, or average HER2
copy number ≥6.0 signals per cell or per current ASCO-CAP (American Society of
Clinical Oncology - College of American Pathologists) or NCCN (National Comprehensive
Cancer Network) guidelines. Note: All histological diagnostic material should be
reviewed at enrolling institution as required per local standards.

- Unresected, untreated breast cancer that meets one of the following clinical stages
(see Appendix A): T2, T3, or T4a-c lesion, any N, M0. Note: Patients with inflammatory
breast cancer (T4d) are not eligible. Bilateral cancers are permitted with approval of
the Protocol Chair.

- ECOG performance status 0-1 (Appendix B)

- Adequate organ function as follows:

1. Absolute neutrophil count (ANC) ≥ 1,500/mm3

2. Platelet count ≥ 100,000/mm3

3. Hemoglobin ≥ 10 g/dL

4. Creatinine ≤ 1.5 times the upper limit of normal with creatinine clearance ≥ 50
mL/min using the Modified Cockcroft-Gault method

5. Bilirubin (total) ≤ 1.5 times upper limit normal (with exception of Gilberts
syndrome)

6. AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 2 times the upper limit of
normal

- Adequate cardiac function as defined by LVEF ≥ 50% on echocardiogram or multi-gated
acquisition scan (MUGA)

- Able and amenable to baseline and follow-up PET/CT imaging and study-specific biopsy
procedures. Note: If there are any imaging concerns that the patient may not be
suitable for quantitative PET/CT (e.g., a metallic device directly overlies the
breast), discussion with the local and central radiologists is required to confirm
eligibility for the trial. Also, it is expected that subjects have all PET/CT imaging
done on pre-qualified machines for the study; if baseline imaging done on another
machine, please contact the Protocol Chair/designee for guidance prior to confirming
eligibility.

- The patient, if of childbearing potential, is willing to use effective, non-hormonal
contraception while on treatment and for at least 6 months following the last dose of
therapy.

- Patient understands the study regimen, its requirements, risks, and discomforts, and
is able and willing to sign an informed consent form.

Exclusion Criteria:

- Received prior or ongoing local (e.g radiation) or systemic treatment (chemotherapy or
endocrine therapy) for the current breast cancer. Patients who received tamoxifen or
raloxifene or another agent for prevention of breast cancer may be included as long as
the patient has discontinued the treatment at least one month prior to baseline study
biopsy.

- Systemic treatment for prior cancer within the last 5 years, with the exception of
adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or
squamous cell carcinoma of the skin.

- Women who are pregnant or nursing

- Current use of any investigational agents

- Known hypersensitivity to trastuzumab or pertuzumab

- Any medical condition that in the opinion of the investigator puts the patient at risk
of potentially serious complications while on this therapy. Specifically, uncontrolled
hypertension (systolic >150 and/or diastolic >100), unstable angina, congestive heart
failure of any New York Heart Association (NYHA) classification, serious cardiac
arrhythmia requiring treatment (exception: atrial fibrillation, paroxysmal
supraventricular tachycardia), history of myocardial infarction within 6 months of
enrollment.