Phase II Neoadjuvant in Inflammatory Breast Cancer

The Study Drugs:

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking
proteins inside the cancer cell, called the Her2/neu receptor and the epidermal growth
factor (EGFR).

Cyclophosphamide, paclitaxel, and 5-fluorouracil are designed to block cancer cells from
dividing, which may slow or stop their growth and their ability to spread throughout the
body. This may cause the cancer cells to die.

Epirubicin is designed to attach to DNA (the genetic material of cells) which may slow or
stop their growth and cause them to die.

Study Drug Administration:

On Weeks 1-24 you will take lapatinib every day by mouth with water (about 8 ounces). It
should be taken at least 1 hour before or at least 2 hours after eating. It is important
that you take the study drug at about the same time every day. You should not eat pamelo
fruit, grapefruit, star fruit, pawpaw, and/or drink their juices while on study.

If you forget to take a dose of the study drug, you should take the missed dose as soon as
you remember, unless it has been more than 12 hours. If it has been more than 12 hours, do
not take the missed dose. Instead, take the next dose as scheduled the next day. If you
vomit after taking the study drug, wait until the next day to take your next dose.

The study drug should be stored at room temperature and out of direct sunlight. The study
drug should be kept away from children. About every 3 weeks, you will need to bring back
your empty or partially used bottle of study drug as instructed by your doctor.

On Weeks 3-12, you will receive paclitaxel through a needle in your vein 1 time a week. The
infusion will take about 1 hour. You will continue to take lapatinib every day.

On Weeks 13-24, you will receive 5-fluorouracil, epirubicin, and cyclophosphamide 1 time
every 21 day study cycle. You will receive 4 cycles. Each 5-fluorouracil infusion will
take about 3-5 minutes, each epirubicin infusion will take about 5-10 minutes, and the
cyclophosphamide infusion will take about 45-60 minutes. You will continue to take
lapatinib every day during Weeks 13-24.

If you experience intolerable side effects, the study doctor may give you drugs to help with
this side effect or change your dose of study drug.

Study Visits:

On Day 1 of Week 1, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your vital signs and weight.

- You will be asked about any drugs that you may be taking.

- You will have a performance status evaluation.

Every 3 weeks while taking combination chemotherapy and study drug, the following tests and
procedures will be performed:

- You will have a physical exam, including measurement of your vital signs and weight.

- You will be asked about any changes in your health and any drugs that you may be
taking.

- You will have a performance status evaluation.

- Your medical history will be recorded.

- Blood (about 3 tablespoons) will be drawn for routine tests.

At Week 6, you will have a CT scan, MRI, and/or a bone scan to check the status of the
disease.

At the end of the chemotherapy treatment, the disease will be measured by physical exam,
chest CT scan and sonogram to check the status of the disease. If the disease has gotten
worse, you will be taken off study. If the disease has gotten worse, you will be taken off
study. Your doctor will discuss your next step of treatment options.

Surgery:

At the end of the chemotherapy period, if the disease has responded well to the drugs, you
will have surgery to remove the breast tumor. You will sign a separate consent form for the
surgery. Either at the end-of-treatment visit at week 24 after you are done with
chemotherapy, or before the surgery, the following tests will be performed:

- You will have a complete physical exam, including measurement of your vital signs and
weight.

- You will have a performance status evaluation.

- You will be asked about any drugs you may be taking.

- Blood (about 3 tablespoons) will be drawn for routine tests

- You will have an ECG.

- You will have a MUGA or echocardiogram to check your hearts health.

- You will have a CT scan, MRI, and/or a bone scan to check the status of the disease.

- You will have a tissue biopsy to check the status of the disease.

Length of Study:

You may continue to receive the study drugs for up to 24 weeks. You will be taken off study
early if the disease gets worse or intolerable side effects occur.

Long-Term Follow-Up:

Once you are off study, you will have follow-up visits at 3 and 6 months after surgery. At
these visits, you will have a MUGA or ECHO performed.

You will have additional visits every 4 months for Years 2 and 3, and then every 6 months
for Years 4 and 5. At these visits, blood (about 3 tablespoons) will be drawn for routine
tests.

This is an investigational study. Lapatinib is FDA approved and commercially available when
taken in combination with capecitabine for another type of breast cancer. Using Lapatinib
in inflammatory breast cancer is investigational.

5-fluorouracil, epirubicin, cyclophosphamide, and paclitaxel are all FDA approved and
commercially available for treating breast cancer. The combination of these drugs is not
currently FDA approved for the treatment of IBC. At this time, this drug combination is
only being used in research.

Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.