preoperative study with trastuzumab, pertuzumab and letrozole in breast cancer patients sensitive to hormonal therapy

Conditions: Endocrine Sensitive HER2+/HR+ Breast Cancer

Summary: 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

Eligibility criteria:
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; \ /=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

Keywords: her2+/hr+ breast cancer