Ph III Trial to Compare Safety and Efficacy of Lapatinib Plus Trastuzumab Plus Aromatase Inhibitor (AI) vs. Trastuzumab Plus AI vs. Lapatinib Plus AI as 1st Line in Postmenopausal Subjects With Hormone Receptor+ HER2+ MBC Who Received Trastuzumab and Endocrine Therapy in Neo- and/or Adjuvant Setting

Inclusion Criteria:

- Signed written informed consent

- Post-menopausal female subjects >=18 years of age. Post-menopausal as defined by any
of the following: Age > 60 years; Age >=45 years with amenorrhea > 12 months with an
intact uterus; Having undergone a bilateral oophorectomy or radiation castration with
amenorrhea for at least 6 months; or FSH and estradiol levels in postmenopausal range
(utilizing ranges from the local laboratory facility). In subjects who have
previously been treated with an GnRH/LHRH analogue, the last injection must have been
administered > 4 months prior to randomization and menses must not have restarted

- Histologically confirmed Stage IV invasive breast cancer. Subjects may have either
measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors
(RECIST 1.1)

- Tumors that are ER+ and/or PgR+ by local laboratory

- Documentation of HER2 overexpression or gene amplification, in the invasive component
of either the primary tumor or metastatic disease site as defined as: 3+ by
Immunohistochemistry (IHC) and/or HER2/neu gene amplification by fluorescence,
chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene
copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome
17 signals) of >=2.0]

- Subject must have received prior neoadjuvant and/or adjuvant trastuzumab

- Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy

- Subjects who have a life expectancy of > 6 months as assessed by the treating
investigator

- Have baseline of Left Ventricular Ejection Fraction (LVEF) >=50% measured by
echocardiography (ECHO) or multi-gated acquisition scan (MUGA)

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

- All prior treatment related toxicities must be CTCAE (Version 4.0) <= Grade 1 at the
time of randomization

- Completion of screening assessments

- Adequate baseline organ function defined by baseline laboratory values

Exclusion Criteria:

- History of another malignancy. Exception: Subjects who have been disease-free for 5
years, or subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible.

- Subjects with extensive symptomatic visceral disease including hepatic involvement
and pulmonary lymphangitic spread of tumor, or the disease is considered by the
investigator to be rapidly progressing or life threatening (subjects who are intended
for chemotherapy)

- Subjects who received prior chemotherapy, hormonal therapy, immunotherapy, biologic
therapy, or anti-HER2 therapy for advanced or metastatic disease

- Serious cardiac illness or medical condition including but not confined to:
Uncontrolled arrhythmias; Uncontrolled or symptomatic angina; History of congestive
heart failure (CHF); Documented myocardial infarction <6 months from study entry

- Known history of, or clinical evidence of, central nervous system (CNS) metastases or
leptomeningeal carcinomatosis

- Current active hepatic or biliary disease (with exception of subjects with Gilbert's
syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
per investigator assessment)

- Concurrent disease or condition that may interfere with study participation, or any
serious medical disorder that would interfere with the subject's safety (for example,
active or uncontrolled infection or any psychiatric condition prohibiting
understanding or rendering of informed consent)

- Have any clinically significant gastrointestinal abnormalities that may alter
absorption such as malabsorption syndrome or major resection of the stomach or bowels

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the study agents or their excipients that, in the
opinion of the Investigator or GSK medical monitor, contraindicates their
participation

- Any prohibited medication as described in the EGF114299 protocol

- Administration of an investigational drug within 30 days or 5 half-lives, whichever
is longer, preceding the first dose of study treatment.