- Patients must have HER2-positive Stage II or III histologically confirmed invasive
carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or
imaging is required.
- HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH
positive based on one of the three following criteria:
- Single-probe average HER2 copy number6.0 signals/cell OR
- Dual-probe HER2/CEP17 <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.
- Bilateral breast cancers are allowed if both cancers are HER2-positive.
- Patients with multifocal or multicentric disease are eligible as long as one area
meets eligibility criteria.
- Breast imaging should include the ipsilateral axilla. For subjects with a clinically
negative axilla, a sentinel lymph node biopsy will be performed either before or
after preoperative therapy at the discretion of the subject's physicians. For
subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN
procedure will be performed to determine the presence of metastatic disease in the
- Men and women (with any menopausal status) 18 years of age
- ECOG performance status 0 or 1
- Required laboratory values:
- ANC 1500/mm3
- Hemoglobin 9 g/dl
- Platelets 100,000/mm3
- Serum creatinine < 1.5 X ULN (institutional)
- Total bilirubin 1.0 X ULN (institutional) For patients with Gilbert syndrome,
the direct bilirubin should be within the institutional normal range.
- AST and ALT 1.5x ULN (institutional)
- Alkaline phosphatase 1.5x ULN (institutional)
- Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is
required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B
core antibody (HBcAb) in addition to HCV antibody testing.
- Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional)
- Left ventricular ejection fraction (LVEF) 55%
- Premenopausal women must have a negative serum pregnancy test, including women who
have had a tubal ligation and for women less than 12 months after the onset of
- 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.
- Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided
during the study treatment period with T-DM1.
- Excessive alcohol intake should be avoided (occasional use is permitted).
- 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.
- 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 enrollment.
- Patients with active liver disease, for example, due to hepatitis B virus, hepatitis
C virus, autoimmune hepatic disorder, or sclerosing cholangitis.
- 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) Grade II or higher, or serious cardiac arrhythmia requiring
- Significant symptoms (Grade 2) peripheral neuropathy.
- Other concurrent serious diseases that may interfere with planned treatment,
including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled
- Any prior treatment for the current breast cancer, including chemotherapy, hormonal
therapy, radiation or experimental therapy.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both