INTRODUCTION

Breast cancer is the most common female cancer in the United States and up to 20 percent of women with breast cancer have tumors that have high levels of HER2, which is a protein that is involved in cell growth, differentiation, and blood vessel formation (angiogenesis). In the past, tumors with high levels of HER2 (also known as HER2-positive tumors) were associated with an increased risk of both recurrence and death from breast cancer. However, with the use of chemotherapy and targeted treatment against HER2, the prognosis of HER2-positive breast cancers has improved substantially.

This article focuses on the adjuvant medical treatment of HER2 positive breast cancer. An introduction to breast cancer and an overview of treatments, including surgery, radiation therapy, and medical therapy, is also available. (See "Patient information: Breast cancer guide to diagnosis and treatment (Beyond the Basics)".) More detailed information is available by subscription. (See "Adjuvant medical therapy for HER2-positive breast cancer".)

WILL I NEED TREATMENT AFTER SURGERY?

After breast cancer is removed with surgery, there is still a risk that cancer cells remain and may return or spread to other parts of the body. Adjuvant therapy is given after surgery to destroy these cells. Adjuvant therapy improves the chance of curing breast cancer and decreases the risk of dying of breast cancer. Thus, adjuvant therapy is a very important part of modern breast cancer treatment for most patients. There are different forms of adjuvant treatment and your doctor will help you decide what is best for you. Some patients need radiation therapy after surgery. For HER2-positive breast cancer, adjuvant medical therapy options include: endocrine therapy and chemotherapy, and HER2-directed treatment, such as trastuzumab (Herceptin). Each works on your cancer differently.

Will I need radiation treatment? — Radiation therapy refers to the use of high-energy x-rays to slow or stop the growth of cancer cells. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays over several days. This prevents the cancer cells from growing further and causes them to eventually die. For patients with breast cancer, adjuvant radiation is given to decrease the risk of the cancer coming back in the breast or chest wall (this is called locoregional recurrence).

Radiation is usually given as external beam radiation, meaning that the radiation beam is generated by a machine that is outside the patient. Exposure to the beam typically takes only a few seconds (similar to having an x-ray). Some patients will need radiation therapy after surgery and you should discuss this option with a radiation oncologist, who is specialized in the use of radiation treatment.

Will I need HER2 directed therapy? — Studies have shown that adjuvant treatment using a combination of HER2 targeted therapy and chemotherapy greatly improves survival of women with HER2-positive breast cancer. In contrast, HER2 targeted therapy by itself is not used in the adjuvant setting. Trastuzumab is the HER2 targeted therapy used in this setting. Trastuzumab is appropriate for most patients with HER2 positive breast cancer. However, some patients with very small tumors (eg, <0.5 cm) may not require trastuzumab therapy after surgery. Your doctor can help you decide if HER2 targeted therapy is right for you.

How is trastuzumab given? — Trastuzumab is given during and then after chemotherapy, for a total treatment duration of 12 months. During chemotherapy, trastuzumab is given with each cycle of chemotherapy. Once your course of chemotherapy is completed, trastuzumab is given by itself, usually every three weeks, for one year.  

What are the side effects of trastuzumab? — The most common side effect of trastuzumab is fever and/or chills. Heart failure develops in about 3 to 5 percent of women treated with trastuzumab. However, trastuzumab-related heart damage may not be permanent.

Will I need chemotherapy? — Chemotherapy is a treatment given to stop the growth of cancer cells. It aims to destroy any remaining cancer cells to increase the chance of cure. This type of chemotherapy is called "adjuvant", which means that it is given after surgery with curative intent. Chemotherapy is given in addition to HER2-directed therapy for most patients with HER2-positive breast cancer. However, some patients with very small tumors (eg, <0.5 cm) may not require chemotherapy after surgery. Your doctor can help you decide if adjuvant chemotherapy is right for you.  

How is chemotherapy given? — Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. This treatment usually involves a combination of several chemotherapy drugs (called regimens). Following surgery, it is usually started within four to six weeks postoperatively, and precedes radiation therapy, if this too has been recommended. Since different combinations of chemotherapy can be used, your doctor will describe which specific chemotherapy drugs will be needed, how long treatment will last, and what side effects are expected from your treatment.

What side effects does chemotherapy cause? — Chemotherapy can cause side effects during and after treatment. The type and severity of these side effects depends upon which chemotherapy drugs are used. Side effects that occur during chemotherapy are usually temporary and reversible. The most common side effects are nausea, vomiting, mouth soreness, temporary lowering of the blood counts, and hair loss. Long term side effects can include premature menopause (ovarian failure), damage to the heart, and a small risk of leukemia.

Will I need endocrine therapy? — Endocrine therapy helps to prevent breast cancer cells from being fed by estrogen and is only indicated for women with estrogen-responsive (ER-positive) or progesterone-responsive (PR-positive) cancers. Not all women with HER2-positive breast cancers have ER- or PR-positive tumors. But, if the tumor is ER- or PR-positive, then you should discuss this option with your doctor.

How is endocrine therapy given? — Endocrine therapy is given after completion of chemotherapy and is given as a pill to be taken every day for five years. More information on endocrine therapy can be found elsewhere. (See "Patient information: Early stage breast cancer treatment in postmenopausal women (Beyond the Basics)" and "Patient information: Early stage breast cancer treatment in premenopausal women (Beyond the Basics)".)

Are there side effects of endocrine treatment? — The side effects of endocrine treatment depend on the drug that you are taking, but common side effects include nausea, mood disturbances, cataracts, and cardiac disease. Tamoxifen can cause vaginal bleeding and clot formation. The aromatase inhibitors (anastrazole, letrozole) can cause bone and joint pain, bone loss (osteopenia) or osteoporosis, which can result in fractures.

WHICH TREATMENT IS RIGHT FOR ME?

There are many options for the adjuvant therapy of breast cancer and deciding which is best can be confusing. Expert guidelines help clarify which treatments are most appropriate for large groups of women. However, individual factors (your preferences, cancer stage) are also important to consider. You should discuss your options for adjuvant therapy with your doctor to determine which therapy is best.

FOLLOW UP AFTER TREATMENT

A summary of the American Society of Clinical Oncology's recommendations for follow up after breast cancer treatment is provided in the following table (table 1).

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient information: Breast cancer (The Basics)
Patient information: Breast reconstruction after mastectomy (The Basics)
Patient information: Choosing treatment for early-stage breast cancer (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient information: Breast cancer guide to diagnosis and treatment (Beyond the Basics)
Patient information: Surgical procedures for breast cancer — Mastectomy and breast conserving therapy (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Adjuvant medical therapy for HER2-positive breast cancer
Adjuvant chemotherapy for hormone receptor-positive or negative, HER2-negative breast cancer
Adjuvant endocrine therapy for hormone receptor-positive breast cancer
Overview of the treatment of newly diagnosed, non-metastatic breast cancer
Diagnostic evaluation of women with suspected breast cancer
General principles on the treatment of early stage and locally advanced breast cancer in older women
Approach to the long-term survivor of breast cancer

The following organizations also provide reliable health information.

• National Cancer Institute

      1-800-4-CANCER
      (www.nci.nih.gov)

• American Society of Clinical Oncology

     (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

     (www.nccn.org)

• American Cancer Society

      1-800-ACS-2345
     (www.cancer.org)

• Adjuvant! Online

      (www.adjuvantonline.com)

• Susan G. Komen Breast Cancer Foundation

      (www.komen.org)

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