A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)

Inclusion Criteria:

- Adult patient, >/= 18 years of age

- HER2-positive breast cancer

- Histologically confirmed invasive breast carcinoma

- Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be
eligible)

- Completion of preoperative systemic chemotherapy and HER2-directed treatment
consisting of at least 6 cycles of chemotherapy with a total duration of at least 16
weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based
therapy

- Adequate excision: surgical removal of all clinically evident disease in the breast
and lymph nodes as specified in protocol

- Pathological evidence of residual invasive carcinoma in the breast or axillary lymph
nodes following completion of preoperative therapy

- An interval of no more than 12 weeks between the date of surgery and the date of
randomization

- Known hormone-receptor status

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Adequate hematologic, renal and liver function

- Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO)
or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no
decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or,
if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after
completion of neoadjuvant chemotherapy.

- For women who are not postmenopausal or surgically sterile: agreement to remain
abstinent or use single or combined contraceptive methods that result in a failure
rate of < 1% per year during the treatment period and for at least 7 months after the
last dose of study drug

- Documentation of hepatitis B virus and hepatitis C virus serology is required

Exclusion Criteria:

- Stage IV (metastatic) breast cancer

- History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in
situ

- Evidence of clinically evident gross residual or recurrent disease following
preoperative therapy and surgery

- Progressive disease during preoperative systemic therapy

- Treatment with any anti-cancer investigational drug within 28 days prior to commencing
study treatment

- History of other malignancy within the last 5 years except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer,
or other non-breast malignancies with a similar outcome to those mentioned above

- Patients for whom radiotherapy would be recommended for breast cancer treatment but
for whom it is contraindicated because of medical reasons

- Current NCI CTCAE (Version 4.0) Grade >/= 2 peripheral neuropathy

- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin >
240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2;
For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2

- Cardiopulmonary dysfunction as defined by protocol

- Prior treatment with trastuzumab emtansine

- Current severe, uncontrolled systemic disease

- Pregnant or lactating women

- Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or
sclerosing cholangitis

- Concurrent serious uncontrolled infections requiring treatment or known infection with
HIV

- History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity
to trastuzumab or murine proteins or any components of the product