Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed advanced breast cancer (metastatic or locally advanced)

- Tumor overexpressing HER2 (HER2 3+ by IHC OR HER2 2+ by IHC and FISH positive) in
samples from the primary and/or secondary tumor

- Measurable or evaluable disease

- Cancer is progressive after treatment with at least 1 line or, at most, 2 lines, of
chemotherapy that included trastuzumab (Herceptin®)

- Patients presenting with treated (surgical resection or radiotherapy) asymptomatic
cerebral metastases or leptomeningeal metastases may be included if they are
neurologically stable and have not received steroids or anticonvulsant treatment for
at least 4 weeks before study entry

PATIENT CHARACTERISTICS:

Inclusion criteria:

- Female

- Menopausal status not specified

- Patients must have an estimated survival of at least 3 months

- WHO performance status (ECOG) 0-2

- Hemoglobin ≥ 9 g/dL

- ANC ≥ 1,500/mm³

- Platelets ≥ 100,000/mm³

- Total bilirubin ≤ 2.5 mg/dL

- ALT and AST ≤ 3 times upper limit of normal

- Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 40 mL/min

- LVEF ≥ 50% (echographic or isotopic method)

- Potentially reproductive patients must agree to use an effective contraceptive method
while on study treatment

- Patients must be affiliated with a Social Security system

Exclusion criteria:

- Uncontrolled cardiac pathology, including any of the following:

- Angina pectoris

- Arrhythmia

- Cardiac insufficiency

- Dysphagia or inability to swallow the vinorelbine ditartrate soft capsules

- Malabsorption syndrome or disease significantly affecting gastrointestinal function

- Preexisting neuropathy (grade ≥ 2)

- Pregnant women, women who are likely to become pregnant, or women who are
breastfeeding

- Any psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule

- Individuals deprived of liberty

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

- At least 3 weeks since prior chemotherapy or trastuzumab

- At least 4 weeks since prior radiotherapy and recovered

- More than 30 days since prior participation in another therapeutic trial using an
experimental drug

- More than 7 days since prior and no concurrent CYP3A4 inhibitors, including the
following:

- Antibiotics: clarithromycin, erythromycin, troleandomycin

- HIV drugs: anti-retrovirals (delavirdine), protease inhibitors (ritonavir,
indinavir, saquinavir, nelfinavir, amprenavir, lopinavir)

- Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole (doses less
than 150 mg/day are allowed)

- Antidepressants: nefazodone, fluvoxamine, fluoxetine

- Calcium channel blockers: verapamil, diltiazem

- Gastric pH modifiers: omeprazole, cimetidine, ranitidine (during course 1 of
study treatment)

- Gastrointestinal drugs: cimetidine, aprepitant

- Grapefruit or grapefruit juice

- More than 14 days since prior and no concurrent CYP3A4 inducers, including the
following:

- Glucocorticoids: dexamethasone or dexamethasone equivalent dose > 1.5mg/day

- Anticonvulsive agents: phenytoin, carbamazepine, phenobarbital

- HIV drugs: efavirenz, nevirapine

- Antibiotics: rifampicin, rifabutin, rifapentine

- Miscellaneous drugs: St. John's wort, modafinil

- At least 6 months since prior and no concurrent amiodarone

Exclusion criteria:

- Prior major resection of stomach or proximal bowel that could affect absorption of
oral drugs

- Prior vinorelbine ditartrate

- Any concurrent plant-based alternative medicine

- Use of antacids (i.e., Maalox, Rennie, Smecta) is not allowed 1 hour before and 1
hour after lapatinib intake

- Concurrent yellow fever vaccine or live attenuated vaccine

- Growth factors for the prevention of neutropenia are not allowed during course 1 of
study treatment