DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC
DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC
This research study is studying whether participants and their doctors are willing to
 determine post-surgery treatment on the basis of response to pre-surgery treatment, and
 studying blood and tissue collected from participants treated with a combination of drugs as
 a treatment for breast cancer.

 The names study drugs involved in this study are:

 -  Paclitaxel (also called Taxol)

 -  Trastuzumab (also called Herceptin)

 -  Pertuzumab (also called Perjeta)
This research study is a Pilot Study, which means investigators are looking at the
 feasibility of a new approach for deciding the optimal medical treatment for this type of
 breast cancer. The FDA (the U.S. Food and Drug Administration) has approved paclitaxel,
 trastuzumab, and pertuzumab as part of a pre-operative treatment option for this disease.

 The purpose of this study is to evaluate whether participants and their doctors are willing
 to accept a treatment recommendation for post-operative chemotherapy, on the basis of the
 participant's response to pre-operative treatment with paclitaxel, trastuzumab, and
 pertuzumab.

 In addition, the investigators are evaluating how the body's immune system works with
 paclitaxel, trastuzumab, and pertuzumab to kill cancer cells. For this reason, the
 investigators will collect samples of the participant's breast tumor and samples of the
 participant's blood over time to understand the reaction of the immune system to the
 participant's tumor.
Inclusion Criteria:

 -  Patients must have Stage II or III (according to AJCC cancer staging manual anatomic
 staging table, 8th edition) histologically confirmed invasive carcinoma of the breast.
 A minimum tumor size of 1.5 cm determined by physical exam or imaging (whichever is
 larger) is required. Patients with inflammatory breast carcinoma (T4d) are NOT
 eligible.

 -  Tumors must be HER-2 positive, as assessed by standard local institutional protocol
 (central testing is not required):

 -  IHC 3+

 -  FISH positive based on one of the three following criteria:

 Single-probe average HER2 copy number ≥ 6.0 signals/cell; OR

 -  Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number ≥ 6.0 signals/cell;
 OR

 -  Dual-probe HER2/CEP17 ratio ≥2.0

 -  ER/PR determination is required. ER- and PR-assays should be performed by
 immunohistochemical methods according to the local institution standard protocol.

 -  Bilateral breast cancers are allowed as long as both cancers are HER2-positive
 (as defined in 3.1.2), or the contralateral cancer is a <1 cm, ER+, and HER2-
 tumor.

 -  Patients with multifocal or multicentric disease are eligible as long as all
 tumor foci that were tested for HER2 status at the local institution are
 HER2-positive, and at least one tumor focus meets eligibility criteria.

 -  Breast imaging should include dedicated ultrasound of the ipsilateral axilla. For
 subjects with a clinically positive axilla based on exam or imaging, a fine
 needle aspiration or core biopsy procedure will be performed to determine the
 presence of metastatic disease in the lymph nodes (though lymph node sampling
 procedure need not be resulted prior to patient's registration on trial, as long
 as all other eligibility are met).

 -  Men and women (with any menopausal status) ≥ 18 years of age are eligible.

 -  ECOG PS 0 or 1.

 -  Required laboratory values:

 -  ANC ≥ 1000/mm3

 -  Hemoglobin ≥ 9 g/dl

 -  Platelets ≥ 100,000/mm3

 -  Serum creatinine < 1.5 x ULN (institutional) OR calculated GFR ≥60mL/min.

 -Total bilirubin ≤ 1.5 x ULN (institutional). For patients with Gilbert Syndrome, the
 direct bilirubin should be within the institutional normal range OR total bilirubin ≤
 2.0 mg/dL.

 -  AST and ALT ≤ 2.5x ULN (institutional)

 -  Left ventricular ejection fraction (LVEF) ≥ 50%.

 -  Premenopausal women must have a negative serum pregnancy test within 14 days of
 registration, including women who have had a tubal ligation and for women less
 than 12 months after the onset of menopause.

 -  Women of childbearing potential and men with partners of childbearing potential
 must be willing to use one highly effective form of non-hormonal contraception or
 two effective forms of non-hormonal contraception by the patient and/or partner
 and continue its use for the duration of the study treatment and for 7 months
 after the last dose of study treatment.

 -  Patients with a history of ipsilateral DCIS are eligible.

 -  Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have
 any contraindications to radiation therapy.

 -  Willing and able to sign informed consent.

 -  Willing to provide tissue for research purposes

 Exclusion Criteria:

 -  Pregnant or nursing women due to the teratogenic potential of the study drugs.

 -  Active, unresolved infection.

 -  Receipt of intravenous antibiotics for infection within 7 days prior to registration.

 -  Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or
 clinically significant (i.e. active) cardiovascular disease: cerebrovascular
 accident/stroke or myocardial infarction within 6 months prior to first study
 medication, unstable angina, congestive heart failure (CHF) of New York Heart
 Association (NYHA) Class II or higher (see Appendix B), or serious cardiac arrhythmia
 requiring medication.

 -  Significant symptoms (Grade ≥ 2) from peripheral neuropathy.

 -  Other concurrent serious diseases that may interfere with planned treatment, including
 severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.

 -  Any prior treatment for the current breast cancer, including chemotherapy, hormonal
 therapy, radiation, or experimental therapy