Patient information: Locally advanced and inflammatory breast cancer (Beyond the Basics)

INTRODUCTION

Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the primary cause of death in women ages 45 to 55. Finding and treating the cancer in the early stages can often lead to a cure.

Occasionally, a breast cancer will not be discovered until it is fairly large or locally advanced. The term locally advanced breast cancer (LABC) is used to describe a breast cancer that has progressed locally but has not yet spread outside the breast and local lymph nodes.

This article will cover the treatment of locally advanced breast cancer, including inflammatory breast cancer. Breast cancer is a very complex topic. An introduction to breast cancer and an overview of treatment is available elsewhere. (See "Patient information: Breast cancer guide to diagnosis and treatment (Beyond the Basics)".)

More detailed information about locally advanced and inflammatory breast cancer is available by subscription.

WHAT IS LOCALLY ADVANCED BREAST CANCER?

Locally advanced breast cancer (LABC) includes:

• Large breast tumors (more than 5 centimeters in diameter)
• Cancers that involve the skin of the breast or the underlying muscles of the chest
• Cancers that involve multiple local lymph nodes (those located in the arm pit or the soft tissues above and below the collarbone)
• Inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory)

Although the likelihood of curing LABC is lower than it would be if the cancer were small and confined to the breast, cure is possible with aggressive treatment. In most cases, this requires a combination of chemotherapy, radiation therapy, and surgery.

SIGNS AND SYMPTOMS

Locally advanced breast cancer (LABC) — Most LABCs can be felt by both the woman and her doctor; the cancer may also be visible.

Inflammatory breast cancer — Inflammatory breast cancer (IBC) is a specific type of LABC that has unique symptoms. IBC often does not produce a lump that can be felt within the breast. Instead, it causes thickening and swelling of the skin of the breast, which may be reddened and warm to the touch, or may resemble the texture of an orange peel. The breast is often painful and enlarged, and appears inflamed.

DIAGNOSIS AND STAGING

Once the diagnosis of a breast cancer is suspected, several tests will be done to confirm the diagnosis. Most women with locally advanced breast cancer have lymph nodes or glands that can be felt in the axilla (arm pit). Testing can be done to confirm this finding and to show what other areas are affected by the cancer.

Mammogram — A mammogram of both breasts is needed to see how large the cancer is and to determine if the opposite breast is affected. A breast magnetic resonance imaging (MRI) or ultrasound may also be recommended.

Biopsy of the tumor — In order to confirm the diagnosis and type of breast cancer, a biopsy is required. The biopsy technique depends upon whether a lump is present in the breast. If the physician feels a lump, the biopsy can often be performed in the office.

If the abnormality is only seen on the mammogram and the breast feels normal, then a test is needed to guide where to perform the biopsy. A mammogram is often used for this purpose. The radiologist finds the abnormality on the mammogram and marks its location, often with a thin wire that is inserted into the abnormal area. A surgeon then uses the wire to know which area to biopsy. This procedure is called a needle localization biopsy.

A doctor will examine the biopsy tissue with a microscope to see if there are signs of cancer. He or she will also perform other tests to see if the tumor is making hormone receptors (ER or PR) and a protein called HER2. These two factors are important in selecting the best treatment.

Hormone receptors — About 50 to 70 percent of breast cancers require the female hormone estrogen (estradiol) to grow; other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce molecules called hormone receptors, which are essential for the cell to use estrogen for growth. These hormone receptors can be estrogen receptors (ER), progesterone receptors (PR), or both.

• If a breast cancer contains hormone receptors, the woman is significantly more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen. These treatments are referred to as endocrine or hormone therapy, and such tumors are referred to as "hormone-responsive".
• Women whose tumors do not contain any hormone receptors are not given endocrine therapy.

HER2 expression — HER2 is a protein that is present on about one-third of breast tumors. Having HER2 determines if the cancer will respond to a medicine called trastuzumab (see 'Trastuzumab (Herceptin®)' below).

TREATMENT OF LOCALLY ADVANCED BREAST CANCER

LABC is often treated with a combination of chemotherapy, surgery, and radiation therapy. (See "Overview of the treatment of newly diagnosed, non-metastatic breast cancer", section on 'Locally advanced breast cancer'.)

Chemotherapy — Chemotherapy refers to medicines used to stop or slow the growth of cancer cells. In most cases, chemotherapy includes a combination of two or more drugs, most often given intravenously (IV). These combinations are referred to as regimens.

Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy refers to the time it takes to give the chemotherapy and then allow the body to recover. A cycle of chemotherapy typically ranges from two to four weeks.

Preoperative chemotherapy — For most women with LABC, chemotherapy is recommended before surgery. Preoperative (also called neoadjuvant) chemotherapy can successfully shrink the breast tumor. In about 30 percent of cases, chemotherapy removes all traces of the cancer from the breast and lymph nodes. This is termed a complete clinical response.

Shrinking a large breast tumor with chemotherapy might allow you to have less aggressive surgery. As an example, it might be possible to remove only the tumor (lumpectomy) rather than the entire breast (mastectomy). (See 'Surgery and radiation therapy' below.)

Endocrine therapy — Breast cancers that produce hormone receptors are responsive to endocrine therapy. In some cases, endocrine therapy is given instead of chemotherapy as the first treatment for locally advanced breast cancer.

• Taking endocrine therapy before surgery (called neoadjuvant therapy) can successfully shrink breast cancers that are hormone-responsive. Endocrine therapy has fewer side effects than chemotherapy (and can be taken by mouth rather than IV). Thus, it might be recommended as a first-line treatment, instead of chemotherapy, for women who are older or who are not healthy enough to tolerate chemotherapy.
• For most women with hormone-responsive LABC, endocrine therapy is recommended after surgery for five or more years. When endocrine therapy is given after surgery, it is referred to as adjuvant therapy. The purpose of this treatment is to get rid of any tumor cells that remain in the body (often termed micrometastases) after surgery.

Adjuvant endocrine therapy is usually started after the entire course of chemotherapy is completed.

Trastuzumab (Herceptin®) — Trastuzumab (Herceptin) is a unique drug that works differently than chemotherapy. It targets a protein called HER2, which is found on the cells of some breast cancers. About 20 percent of breast cancers express very high levels of HER2, and trastuzumab appears to work only in this group of women (see 'HER2 expression' above).

Surgery and radiation therapy — Following chemotherapy, tests are performed to see how the tumor responded to treatment. You will have an exam and imaging studies (using mammography, breast ultrasound, or MRI) to see how much of the cancer remains. If there are still signs of cancer, surgery may be recommended.

• A surgery to remove part of the breast (called breast-conserving surgery) is an option for many women with LABC, as long as there are no signs of inflammatory breast cancer (see 'Inflammatory breast cancer' above).
• Mastectomy (total removal of the breast) is necessary if skin involvement has not improved following chemotherapy or if the tumor is still fixed to the underlying chest wall.

After surgery, radiation therapy is recommended to women who had breast conserving surgery. This can significantly lower the chance that the tumor will come back in the remaining breast tissue. (See "Radiation techniques for locally advanced breast cancer".)

Women who have had a mastectomy will likely receive radiation therapy to the chest wall and possibly to the lymph nodes as well. This is especially true if there were involved lymph nodes or inflammatory breast cancer. Having a combination of surgery and radiation therapy decreases the chance that the breast cancer will return in the breast or the chest wall. (See "Postmastectomy chest wall irradiation".) Radiation therapy is given every day (five days a week) for a period of six to seven weeks.

INFLAMMATORY BREAST CANCER

The treatment of inflammatory breast cancer is similar to that of other types of locally advanced breast cancer (LABC). Treatment usually includes chemotherapy, surgery, and radiation therapy. As with other forms of LABC, two types of chemotherapy agents (anthracyclines and a taxane) are usually used.

One difference in the treatment of IBC is that a mastectomy is usually recommended, even if the cancer responded well to neoadjuvant chemotherapy. After mastectomy, radiation therapy to the chest wall and lymph nodes is strongly recommended.

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: Inflammatory 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: Lymphedema after breast cancer surgery (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.

Overview of the treatment of newly diagnosed, non-metastatic breast cancer
Inflammatory breast cancer: Clinical features and treatment
Radiation techniques for locally advanced breast cancer
Inflammatory breast cancer: Pathology and molecular pathogenesis
Neoadjuvant therapy for breast cancer: Rationale, pretreatment evaluation, and therapeutic options
Neoadjuvant systemic therapy for breast cancer: Response, subsequent treatment, and prognosis

The following organizations also provide reliable health information.

• National Cancer Institute 1-800-4-CANCER
  
  (www.nci.nih.gov)
• People Living With Cancer: The official patient information website of the American Society of Clinical Oncology
  
  (http://breastca.asco.org)
• National Comprehensive Cancer Network
  
  (www.nccn.com)
• American Cancer Society 1-800-ACS-2345
  
  (www.cancer.org)
• National Library of Medicine
  
  (www.nlm.nih.gov/medlineplus)
• 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
  
  (http://breastcancer.about.com/forum)

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