The purpose of this study is to evaluate the activity of molecular response in endocrine sensitive breast cancer HER2+/HR+ patients treated with Pertuzumab-trastuzumab plus Ietrozole.

The purpose of this study is:

• to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes.
• to estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US)
• to estimate the percentage of breast conservative surgery
• to evaluate the safety profile
• To perform correlative biomarker analyses

Inclusion Criteria:

• primary diagnosis of infiltrating breast cancer

• HR positivity (ER ≥ 10% and/or PgR ≥10%) and HER2 positivity (IHC 3+ or FISH/CISH amplification), as assessed by local laboratory.

• Stage II-IIIA

• age >18 yrs

• ECOG Performance Status 0-1

• Postmenopausal status, defined by at least one of the following:

  60 years of age; < 60 years of age and amenorrheic for >/=12 months prior to day 1 < 60 years of age, without a uterus, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months

• Cardiac ejection fraction within the institutional range of normal (as measured by echocardiogram or MUGA scan).

• Normal organ and marrow function as defined below:

(leukocytes >=3000/mcL; absolute neutrophil count >=1,500/mcL; platelets >=100,000/mcL; total bilirubin within 1.25 x normal institutional limits (with the exception of Gilbert's syndrome); AST (SGOT)/ALT(SGPT) within 1.25 x institutional upper limit of normal creatinine within normal institutional limits

• Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Stage IIIB, IIIC, and inflammatory breast cancer
• Stage IV breast cancer
• Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with HER2 targeting therapies
• LVEF below the ULN
• Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication.
• Received any investigational treatment within 4 weeks of study start.
• Subjects with known infection with HIV, HBV, HCV
• Known hypersensitivity to any of the study drugs or excipients.
• Dyspnoea at rest or other disease requiring continuous oxygen therapy.
• Psychiatric illness/social situations that would limit compliance with study requirements
• Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol