IRB decision

Hormone receptor positive breast cancer is the most common type of breast cancer, comprising 70-80% of all breast cancers. Endocrine therapy is the main type of initial treatment for patients with your type of breast cancer. Endocrine therapy is treatment that tries to remove, or block certain hormones from binding to the cancer cells and thus slow or stop the growth of cancer. Although most patients with your type of breast cancer respond initially to endocrine therapies, it can lose its effectiveness. New therapies for this type of cancer are needed.

Endocrine therapy forms the backbone of treatment for both early stage and advanced stage hormone receptor positive breast cancer. Although most patients with advanced estrogen receptor positive metastatic disease respond initially to endocrine therapies, this response is short lived. New therapies able to provide additional benefit to patients with hormone receptor positive, endocrine-resistant, advanced metastatic breast cancer are required. This study proposes to add lapatinib to endocrine therapy to treat hormone receptor positive HER-2 negative metastatic breast cancer patients.

Inclusion Criteria

• Histologically or cytologically confirmed invasive breast cancer, which at time of study entry is either stage III (locally advanced) disease not amenable to curative therapy or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease recurrence is available.
• ER and/or Progesterone Receptor (PgR )positive breast cancer (10% or more of infiltrating cancer cells exhibit nuclear staining for ER and/or PgR)
• Have had progressive disease or development of new metastatic disease while on treatment or within 12 months of treatment with an aromatase inhibitor and/or Fulvestrant in adjuvant or metastatic setting
• Have measurable (defined as at least 1 lesion that can be accurately measured in at least 1 dimension [longest diameter to be recorded], with minimum lesion size ≥ 2cm on conventional measurement techniques or ≥ 1cm on spiral computed tomography [CT] scan), or evaluable disease. Patients with lytic or blastic bone disease as only site of disease will be eligible for the study. These patients will be evaluable for progression but not for response.
• Primary tumor was HER-2 negative (IHC 0 or IHC 1+/2+ and Fluorescence in situ hybridization [FISH] ≤ 1.9)
• Patients could have received prior Tamoxifen either as adjuvant therapy or for stage IV disease
• Performance status of 2 or better per Eastern Cooperative Oncology Group (ECOG) criteria
• Adequate cardiac function (cardiac ejection fraction ≥ 50% as measured by echocardiogram or multigated acquisition (MUGA) scan).
• IV bisphosphonate and denosumab for bony metastatic disease will be allowed
• Palliative radiation therapy to bony metastases will be allowed
• Adequate bone marrow function per good medical practice. Results of these tests do not determine eligibility. Minor deviations are acceptable if they do not impact safety in the judgment of the treating physician. Absolute neutrophil count (ANC) ≥ 1500/mm3, platelet count ≥ 100,000/mm3, and hemoglobin ≥ 10 g/dL
• Adequate kidney function: serum creatinine of ≤ 1.5mg/dl and/or creatinine clearance of ≥ 60 mL/min
• Adequate hepatic function: transaminases < 2 x upper limit of normal and total bilirubin ≤ 1.5 mg/dL.
• Must have a serum albumin ≥ 3.0 g/dL.
• Must be informed of investigational nature of study and must sign informed consent in accordance with institutional rules.
• Pretreatment lab values must be performed within 14 days of patient registration and other baseline studies within 30 days.
• Patients will have a baseline bone scan, Computerized Tomography (CT) chest, abdomen and pelvis or Positron Emission Tomography (PET)/CT.
• If previously treated brain metastasis and free of central nervous system (CNS) symptoms and > 3 months from treatment of brain metastasis are eligible

Exclusion Criteria

• Prior HER-2 targeted therapy for metastatic disease

• Has uncontrolled brain metastasis or leptomeningeal disease

• Has rapidly progressing and/or bulky disease which in the opinion of the investigator may be more appropriately treated with a chemotherapy-based strategy.

• Has an uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring parenteral antibiotics or psychiatric illness/social situations that would limit compliance with study requirements.

• Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors

• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (eg, Crohn's, ulcerative colitis).

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

• Renal function as measured by creatinine clearance <3 0ml/min (ratio to norm < 0.1)

• HIV-positive patients receiving combination antiretroviral therapy

• Pregnant women

• Active cardiac disease defined as:

  • History of uncontrolled or symptomatic angina
  • History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
  • Myocardial infarction < 6 months from study entry
  • Uncontrolled or symptomatic congestive heart failure
  • Ejection fraction below institutional normal limit
  • Any other cardiac condition, which in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient

• History of another primary cancer, with exception of:

  • curatively resected nonmelanomatous skin cancer
  • curatively treated cervical carcinoma in-situ
  • other primary solid tumor curatively resected treated with no known active disease present and no treatment administered for the last 3 years.

• Life expectancy of < 2 months

5 years (2009-2014)