Preoperative Study With Trastuzumab, Pertuzumab and Letrozole in Breast Cancer Patients Sensitive to Hormonal Therapy

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