Identification of Early Markers of Response and Resistance to Trastuzumab in Patients With Localized Human Epidermal Growth Factor Receptor-2(HER-2)-Positive Breast Cancer Candidates for Breast Conserving Surgery
- Signed written informed consent
- Female patients aged 18 years or older.
- Histologically or confirmed untreated invasive carcinoma of the breast
- Previous treated invasive breast carcinoma or ductal carcinoma in situ are allowed,
assuming there is no evidence of disease at the moment of the inclusion in the
protocol, and patients are not on any current treatment
- Candidates for breast conserving surgery: patients with a minimum size of 11 mm
measured by breast US. Bilateral and multifocal tumors are allowed, assuming the
biopsies pre- and post-treatment are performed in the same target lesion.
- HER2-positive (defined as either immunohistochemistry [immuno-histochemistry ] 3+ or
in situ hybridization [ISH] positive) as assessed by local laboratory on primary
tumor (ISH positivity is defined as a ratio of 2.2 or greater for the number of HER2
gene copies to the number of signals for abnormality on chromosome 17 (CEP17), or for
single probe tests, a HER2 gene count greater than 4).
- No evidence of metastatic disease (bone scan, X-ray thorax and abdominal US required
previous to the inclusion)
- Eastern Cooperative Oncology Group (ECOG) performance status 0/1.
- Left ventricular ejection fraction (LVEF) of at least 50%
- Negative pregnancy test in women of childbearing potential (premenopausal or less
than 12 months of amenorrhea post-menopause, and who have not undergone surgical
- For women of childbearing potential who are sexually active, agreement to use a
highly effective, non-hormonal form of contraception or two effective forms of
non-hormonal contraception during and for at least 6 months post-treatment.
- Patients non-candidate for breast conserving surgery or patient's candidate for
- Patients receiving another concomitant anticancer treatment like chemotherapy,
immunotherapy, anti-HER2 treatment other than trastuzumab, endocrine treatment, or
- Known hypersensibility to trastuzumab
- Serious uncontrolled concomitant disease that would contraindicate the use of
trastuzumab or that would put the patient at high risk for treatment-related
- Inadequate organ function, evidenced by the following laboratory results:
- Absolute neutrophil count <1,500 cells/mm3
- Platelet count <100,000 cells/mm3
- Hemoglobin <9 g/dL
- Total bilirubin greater than the upper limit of normal (ULN) (unless the patient has
documented Gilbert's syndrome)
- Aspartate aminotransferase (AST [serum glutamate oxaloacetate transaminase]) or
alanine aminotransferase (ALT [serum glutamate pyruvate transaminase]) >2.5 x ULN
- Serum creatinine >2.0mg/dL or 177mol/L
- International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
or partial thromboplastin time (PTT) >1.5 x ULN (unless on therapeutic coagulation)
- Uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) 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 of New York Heart Association
(NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.
- Current known infection with human immunodeficiency virus (HIV), hepatitis B or C
- Assessed by the investigator to be unable or unwilling to comply with the
requirements of the protocol.
- Pregnant or breastfeeding patients