Version May 2024
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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 a protein called "human epidermal growth factor receptor 2" (HER2). Because HER2 is involved in the growth of cancer cells, this type of breast cancer can be aggressive.
It's important that anyone diagnosed with breast cancer be tested for the presence of HER2. 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 treatment of HER2-positive breast cancer. An introduction to breast cancer and an overview of the available treatments, including surgery, radiation therapy, and medication therapy, is also available. (See "Patient education: Breast cancer guide to diagnosis and treatment (Beyond the Basics)".)
CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.
In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.
APPROACH TO TREATMENT — In general, treatment options may include surgery, HER2-directed therapy, endocrine therapy, and radiation therapy. The best combination of treatments, and the order in which to get them, can vary depending on the situation.
Doctors use the following terms to describe cancer therapy according to when it is given:
●"Neoadjuvant therapy" refers to treatment given before surgery, with the goal of reducing the tumor's size before it is removed.
●"Adjuvant therapy" refers to treatment given after surgery, with the goal of destroying any cancer cells that might remain in the body (and potentially spread).
The treatment of HER2-positive breast cancer will depend on your preferences as well as the characteristics of your cancer:
●Many women with HER2-positive breast cancer will get neoadjuvant chemotherapy first, along with medication that targets HER2 directly (see 'Chemotherapy' below and 'HER2-directed therapy' below). Following surgery, these women will get additional (adjuvant) therapy with a HER2-directed medication.
●Some women (particularly those with smaller tumors) will get surgery first, followed by adjuvant therapy consisting of both chemotherapy and HER2-directed therapy. (See 'Chemotherapy' below and 'HER2-directed therapy' below.)
●Women whose cancer is "hormone receptor positive," meaning it requires estrogen to grow, may also be offered endocrine therapy. Doctors can do tests to determine whether your breast cancer falls into this category. (See 'Endocrine therapy, for cancers that are ER positive and HER2 positive' below.)
Surgery — Surgery to remove the tumor is a significant part of treatment for early breast cancer. As discussed above, many women with HER2-positive breast cancer will be offered neoadjuvant therapy prior to surgery. More information about surgery for breast cancer is available separately. (See "Patient education: Surgical procedures for breast cancer — Mastectomy and breast-conserving therapy (Beyond the Basics)".)
Chemotherapy — Chemotherapy refers to medications given to stop the growth of cancer cells. It is given along with HER2-directed therapy, often before surgery, for women with HER2-positive breast cancer.
How is chemotherapy given? — Chemotherapy is not given every day, but instead is given in cycles. A cycle of chemotherapy (which is typically 14 or 21 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). When given as adjuvant therapy, it is usually started within four to six weeks after surgery, and before radiation therapy (if this, too, has been recommended) (see 'Radiation therapy' below). Since different chemotherapy regimens are available, your doctor will describe which specific drugs you will get, how long treatment will last, and what side effects you might experience.
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, hair loss, and a decrease in the number of white blood cells (which can raise your risk of infection). Long-term side effects can include premature menopause (ovarian failure), damage to the heart, and a small risk of leukemia.
HER2-directed therapy — Most women with HER2-positive breast cancer will receive one or more chemotherapy drugs plus trastuzumab, the anti-HER2 antibody. Many studies have shown that these treatments dramatically improve survival for women with HER2-positive breast cancer. Trastuzumab and chemotherapy are even recommended for women with very small, HER2-positive breast cancers. Tumors as small as 0.5 cm often warrant such treatment. However, decisions must be individualized based on your own individual risk. Talk to your doctor about whether you are a candidate for trastuzumab, especially if you have a small HER2-positive breast cancer.
How is trastuzumab given? — Trastuzumab is given intravenously (by IV). It may be given on a weekly schedule or once every three weeks. When it is part of neoadjuvant therapy, you will get trastuzumab along with chemotherapy; your oncologist will use a chemotherapy regimen that can be given along with trastuzumab (some types of chemotherapy drugs are not given at the same time as trastuzumab and might be given separately). Neoadjuvant therapy is typically administered for between 12 and 20 weeks, depending on the chosen regimen, and followed by surgery. When given as adjuvant chemotherapy following surgery, trastuzumab is given concurrently with chemotherapy, then continued for a total duration of 12 months.
What are the side effects of trastuzumab? — The most common side effect of trastuzumab is fever and/or chills. Heart failure develops in approximately 3 to 5 percent of women treated with trastuzumab. However, trastuzumab-related heart damage may not be permanent.
Other anti-HER2 agents — Some women also get a second medication, pertuzumab, along with trastuzumab. However, pertuzumab is associated with side effects, including diarrhea, anemia (having too few red blood cells), and neutropenia (low levels of neutrophils, which are a type of white blood cell). It's also not clear whether the addition of pertuzumab impacts long-term survival rates.
Another option for certain women is a medication that combines trastuzumab with a drug called emtansine (this combination drug is called T-DM1). This can be given to women who received neoadjuvant therapy (before surgery) with chemotherapy and trastuzumab, but still have residual disease at the time of surgery.
Endocrine therapy, for cancers that are ER positive and HER2 positive — More than half of breast cancers require the female hormone estrogen to grow, while other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce proteins called "hormone receptors"; these can be estrogen receptors (ER), progesterone receptors (PR), or both.
If your breast cancer is "hormone receptor positive" (ie, dependent on estrogen and/or progesterone), you may benefit from endocrine therapy. This involves medications that lower estrogen levels or block the actions of estrogen.
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 at least five years. More information on endocrine therapy is available elsewhere. (See "Patient education: Treatment of early-stage, hormone-responsive breast cancer in postmenopausal women (Beyond the Basics)", section on 'Endocrine therapy options' and "Patient education: Treatment of early-stage, hormone-responsive breast cancer in premenopausal women (Beyond the Basics)", section on 'Endocrine therapy options'.)
Are there side effects of endocrine therapy? — 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 (a medication commonly used for endocrine therapy) can cause vaginal bleeding and clot formation. Other drugs called aromatase inhibitors (anastrozole, letrozole) can cause bone and joint pain, bone loss, or fractures.
Radiation therapy — 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 treating breast cancer, radiation is given after surgery 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 women will need radiation therapy after surgery; you should discuss your options with a radiation oncologist, who is specialized in the use of radiation treatment.
WHICH TREATMENT IS RIGHT FOR ME? — There are many options for the treatment 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 (including your personal values and preferences as well as your cancer stage and characteristics) are also important to consider. You should discuss your treatment options with your doctor to determine an approach that you are both comfortable with.
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 table (table 1).
WHERE TO GET MORE INFORMATION — Your health care 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 health care 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 education: Breast cancer (The Basics)
Patient education: Breast reconstruction after mastectomy for cancer (The Basics)
Patient education: Choosing surgical 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 education: Breast cancer guide to diagnosis and treatment (Beyond the Basics)
Patient education: 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 systemic therapy for HER2-positive breast cancer
Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer
Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer
Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer
Diagnostic evaluation of suspected breast cancer
Overview of the approach to early breast cancer in older women
Approach to the patient following treatment for breast cancer
The following organizations also provide reliable health information.
●National Cancer Institute
1-800-4-CANCER
●American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)
●American Cancer Society
1-800-ACS-2345
(www.cancer.org)
●Adjuvant! Online
(http://www.newadjuvant.com/default2.aspx)
●Susan G. Komen Breast Cancer Foundation
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