Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Neoplasms, Breast Female At least 18 years of age Written informed consent to participate in the study Diagnosis of advanced breast cancer. Furthermore, for patients being considered for second-line study treatment only: The patient has received a first-line chemotherapy together with Herceptin or Herceptin alone for her metastatic breast disease meeting all of the following conditions: i) For patients who have received a first-line chemotherapy together with Herceptin The administration of chemotherapeutic agent(s) has been stopped for at least 3 months, or will have been stopped for at least 3 months by the time of the first study vaccination, and The administration of Herceptin alone was maintained after chemotherapy. ii) The last dose of Herceptin was given not less than 3 weeks before the study vaccination. iii) The patient will not be given Herceptin during the trial A tumor lesion from the patient biopsied before or during screening, shows either i) overexpression of the HER2 protein, as determined by IHC (result: IHC 3+), or ii) amplification of the HER2 gene as determined by FISH (at least 4-fold, i.e., at least 8 copies) For patients being considered for first-line study treatment only: The patient's metastatic disease affects the skin and/or the lymph nodes and/or the lungs, but no other organ (with the exception of asymptomatic bone lesions). For patients being considered for second-line study treatment only: The patient's metastatic disease may affect any organ(s) with the exception of the central nervous system (CNS)  For patients being considered for first-line study treatment only Received any chemotherapy for metastatic breast disease Received >300 mg/m2 doxorubicin (cumulative dose) or >600 mg/m2 epirubicin (cumulative dose) Although hormone therapy as a first-line therapy for metastatic disease is accepted, it must NOT have been started or modified (in nature or dosage) within the 12 weeks before the first study vaccination, and NO such change during the study period may be anticipated Treatment with bisphosphonate the bisphosphonate treatment was initiated more than 3 months before first study vaccination Received any investigational or non-registered drug or vaccine other than the study vaccine within the 30 days preceding the first dose of study vaccine, or plans to receive such a drug during the study period For patients being considered for first-line study treatment, any of the following will result in of the patient: 1. Any organ other than skin, lymph nodes, bone and lung is affected by the metastatic disease. 2. If the lung is affected: >3 lung lesions have been detected. 3. If the lung is affected: Any lesion measures 30 mm or more (longest diameter). 4. If the lung is affected: The lung metastases cause any functional impairment. 5. The sponsor may during the study instruct sites that no further patients with lung metastases are to be included. Receipt of such instructions from the sponsor constitutes an criterion for all further patients with lung metastases.For patients being considered for second-line study treatment, the presence of lung metastases that cause any functional impairment following will result in of the patient The patient has a history of congestive heart failure or difficult-to-control hypertension, hypercholesterolemia or diabetes The patient has known coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy (found by ECG) or previous myocardial infarction The patient has any acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests