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Adjuvant medical therapy for HER2 positive breast cancer

Adjuvant medical therapy for HER2 positive breast cancer
Author:Harold Burstein, MD, PhD
Section Editor:Daniel F Hayes, MD
Deputy Editor:Don S Dizon, MD, FACP

 

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".) More detailed information is available by subscription. (See "Adjuvant chemotherapy and trastuzumab for HER2-positive early stage 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.

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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, <1 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.

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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" and "Patient information: Early stage breast cancer treatment in premenopausal women".)

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 every four months 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.

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Patient Level Information:

Patient information: Breast cancer guide to diagnosis and treatment
Patient information: Surgery for breast cancer — Mastectomy and breast conserving therapy

Professional Level Information:

Adjuvant chemotherapy and trastuzumab for HER2-positive early stage breast cancer
Adjuvant chemotherapy for early stage HER2-negative breast cancer
Adjuvant endocrine therapy for postmenopausal women with early stage breast cancer
Adjuvant endocrine therapy for premenopausal women with early stage breast cancer
Adjuvant systemic therapy for older women with early stage breast cancer
An overview of breast cancer
Diagnostic evaluation of women with suspected breast cancer
Follow-up for breast cancer survivors: Recommendations for surveillance after therapy
General principles of management of early breast cancer in older women

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.com)

  • American Cancer Society

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

  • Adjuvant! Online

(www.adjuvantonline.com)

  • Susan G. Komen Breast Cancer Foundation

(www.komen.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

  • About.com Breast Cancer Forum

(file://breastcancer.about.com/forum)

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REFERENCES

  1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365:1687.
  2. Bertelsen L, Bernstein L, Olsen JH, et al. Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the Women's Environment, Cancer and Radiation Epidemiology Study. J Natl Cancer Inst 2008; 100:32.
  3. Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 2006; 295:1658.
  4. Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 2007; 18:1133.
  5. Olivotto IA, Bajdik CD, Ravdin PM, et al. Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 2005; 23:2716.
  6. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25:5287.

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