Tolerability of the Combination of Lapatinib and Trastuzumab in Adults Age 60 or Older With HER2 Positive Locally Advanced or Metastatic Breast Cancer

Inclusion Criteria:

- Locally advanced or metastatic Her2/Neu positive breast cancer (defined as
immunohistochemistry [IHC] 3+ or a fluorescence in situ hybridization [FISH] ratio of
>= 2.0); this may be on either a primary tumor or a metastatic site, and there is no
time limit from the time the specimen was obtained

- Both measurable and non-measurable disease are allowed

- Life expectancy of greater than 12 weeks

- Women of child-bearing potential and sexually active men must agree to use adequate
contraception prior to study entry for six months following duration of study
participation

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2(Karnofsky
performance status >= 60%)

- Hemoglobin >= 10 g/dL (after transfusion if necessary)

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/aspartate aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Creatinine clearance >= 30 mL/min as measured using either the Cockroft-Gault method
or 24-hour creatinine clearance

- The above tests must be obtained within 14 days of study enrollment

- Cardiac ejection fraction >= 50% as measured by echocardiogram of multiple gated
acquisition scan (MUGA) scan

- The ability to swallow and retain oral medication

- Prior treatment with lapatinib or trastuzumab are allowed, provided that the agents
have never been given in combination

- Any number of prior cancer treatments, including investigational agents,
chemotherapy, hormone therapy, or targeted therapy are allowed

- All patients must have the ability to understand and the willingness to sign a
written informed consent

Exclusion Criteria:

- Concurrent investigational treatment, chemotherapy, or targeted therapy; prior
chemotherapy, hormonal therapy, targeted therapy, and investigational agents are
allowed but all toxicities grade >= 2 must have resolved by the time of study
commencement (except alopecia)

- Unstable or symptomatic brain metastases (however, patients with stable or treated
brain metastases who do not require steroids at doses above those permitted for
control of symptoms may be enrolled)

- History of allergic reactions attributed to compounds of similar chemical or
biological composition to lapatinib or trastuzumab

- Concomitant medications listed are prohibited; inhibitors or inducers of CYP3A4 not
listed can be used with caution

- Ongoing or active infection (including human immunodeficiency virus [HIV]) or
psychiatric illness/social situations that would limit compliance with study
requirements

- Inability to take oral medication

- Malabsorption syndrome, (prior surgical procedures affecting absorption), or
inflammatory GI disease (e.g., Crohn's, ulcerative colitis) which in the opinion of
the study coordinator is likely to limit normal absorption of the drug

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

- History of documented congestive heart failure (CHF) or systolic dysfunction (left
ventricular ejection fraction [LVEF] < 50%)

- High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade
atrio-ventricular (AV)-block, supraventricular tachycardias which are not adequately
rate-controlled)

- Angina pectoris requiring antianginal medications

- Evidence of transmural infarction on electrocardiogram (ECG)

- Clinically significant valvular heart disease

- Poorly controlled hypertension (e.g. systolic > 180mm HG or diastolic > 100mm Hg)

- Any other cardiac condition, which in the opinion of the treating physician would
make this protocol unreasonably hazardous for the patient

- Subjects who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study are not eligible