Patient information: Locally advanced and inflammatory breast cancer

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 available treatments are available elsewhere. (See "Patient information: Breast cancer guide to diagnosis and treatment".)

WHAT IS LOCALLY ADVANCED BREAST CANCER?

LABC includes large breast tumors (more than 5 centimeters in diameter), those that involve the skin of the breast or the underlying muscles of the chest wall, and cancers that have extensive involvement of the local lymph nodes (those located in the axilla or in the soft tissues above and below the collarbone). It also includes 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 (palpated) by both the patient and her doctor; they 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 distinct mass or 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 (picture 1 and picture 2). The breast is often painful and enlarged, and appears inflamed.

DIAGNOSIS AND STAGING

Once the diagnosis of a breast cancer is suspected, several tests must be done to confirm the diagnosis and establish the extent of tumor involvement, both within the breast and elsewhere in the body.

Mammogram — A mammogram of both breasts is needed to see how large the cancer is and to determine if the opposite breast is affected. Other tests such as a breast magnetic resonance imaging (MRI) or ultrasound may also be recommended (picture 3).

Biopsy of the tumor — In order to confirm the diagnosis and type of breast cancer, a biopsy is required. A needle biopsy of the tumor, performed in the office, is usually done so that a pathologist can examine the tissue under the microscope.

The pathologist will also perform other tests to determine 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 hormone receptors are present within a breast cancer, 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 therapies, and such tumors are referred to as "hormone-responsive". In contrast, women whose tumors do not contain any ER or PR do not benefit from adjuvant endocrine therapy.

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

Staging workup — Once the diagnosis of breast cancer is established, additional tests are performed to stage the cancer (determine how far it has spread). The stage of a breast cancer is based upon tumor size, involvement of the skin, chest wall or regional lymph nodes, and whether the cancer has spread to the bones or other organs (called metastasis).

Breast cancer stages range from stage I to IV. A description of each stage is provided in table (table 1). Locally advanced breast cancer is stage III disease, and the presence of inflammatory breast cancer makes the cancer a stage IIIB cancer.

In contrast, women who have stage I or II breast cancer are referred to as having early stage disease, while stage IV means that spread to other organs has taken place.

Lymph nodes — The majority of patients with locally advanced breast cancer have lymph nodes or glands that can be felt in the axilla (arm pit). Testing may be done to confirm this finding.

Sentinel node biopsy — The sentinel lymph node (SLN) concept is based on the idea that tumor cells first involve one or a few lymph nodes before involving other nodes or spreading elsewhere. To identify a sentinel lymph node, the surgeon injects dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes.

If a sentinel lymph node (SLN) is identified, it is removed and examined under the microscope. If this node is does not contain any cancer cells, there is a small chance that other axillary nodes will be positive and a full ALND is not necessary [1]. In contrast, if the SLN is positive, there is a chance that other nodes will contain tumor cells, and a full ALND is usually recommended.

Sentinel node biopsy is only appropriate for women who do not have evidence or suspicion of involved lymph nodes on physical examination. In such cases, a full axillary dissection is needed.

Guidelines from the American Society of Clinical Oncology recommend against the routine use of sentinel node biopsy for large breast cancers (>5 cm), tumors that are fixed or attached to the skin or chest wall, and inflammatory breast cancers [1]. However, many clinicians feel that SLN biopsy is an acceptable way of assessing the status of the axillary lymph nodes in patients with a large breast cancer (>5 cm) who do not have enlarged axillary lymph nodes on physical examination, as long as the tumor is not fixed to the skin or underlying chest wall and there is no inflammatory component.

TREATMENT OF LOCALLY ADVANCED BREAST CANCER

LABC is most often treated with combination chemotherapy, surgery, and radiation therapy.

Chemotherapy — Chemotherapy refers to the use of medicines 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. The drugs themselves are usually not administered daily but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to administer the individual drug components of each regimen and then allow the body to recover from the effects of the medicines. A cycle of chemotherapy typically ranges from two to four weeks.

Preoperative chemotherapy — For most women with LABC, chemotherapy is the first component of the treatment, before surgery. Preoperative (also called neoadjuvant) chemotherapy can successfully shrink the breast tumor, and in as many as one-third of cases, it completely removes all traces of the cancer from the breast and lymph nodes. This is termed a complete clinical response. Successful shrinkage of a large breast tumor can increase a woman's options for subsequent surgery. As an example, it might allow selected women to consider breast conserving surgery, in which only the tumor is removed (lumpectomy) rather than the entire breast (mastectomy). (See 'Surgery and radiation therapy' below.)

Although the entire course of chemotherapy is often administered before surgery, it may also be divided between the preoperative and postoperative periods.

Endocrine therapy — As noted above, breast cancers that produce hormone receptors are responsive to endocrine therapy. In some cases, endocrine therapy may be used instead of chemotherapy as the initial treatment for a LABC.

Preoperative endocrine therapy — The preoperative (neoadjuvant) use of endocrine therapy can successfully shrink breast cancers that are hormone-responsive. Because endocrine therapy is generally better tolerated than chemotherapy (and can be given by mouth rather than intravenously), it may be recommended first for women whose organ function is impaired, if a woman wants to avoid chemotherapy-related toxicity, or for those who are physically debilitated.

Postoperative (adjuvant) endocrine therapy — For most women with hormone-responsive LABC, endocrine therapy is recommended after surgery for five or more years. When endocrine therapy (or chemotherapy) is given after surgery, it is referred to as adjuvant therapy, and its purpose is to eliminate any tumor cells that remain in the body (often termed micrometastases) following surgery.

Adjuvant endocrine therapy is usually started after the entire course of chemotherapy is completed because of concerns that the two treatments will interact if given together. However, endocrine therapy can be started during the radiation treatment.

Trastuzumab (Herceptin®) — Trastuzumab (Herceptin) is a unique drug that works by a different mechanism than chemotherapy. It is an antibody that specifically targets a protein called HER2, which is present on the cells of some breast cancers. About 20 percent of breast cancers express very high levels of this marker, and trastuzumab appears to be effective only in this group of women (see 'HER2 expression' above.

Surgery and radiation therapy — Following chemotherapy, tests are performed to assess how the tumor responded to treatment. A physical examination and repeat imaging studies (using mammography, breast ultrasound, or MRI) are conducted to measure the extent of disease that remains in the breast and regional lymph nodes. Breast surgery may then be performed.

Breast-conserving surgery (such as a lumpectomy) is an option for many women with LABC, as long as they do not have 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 (figure 1).

After surgery, radiation therapy to the remaining breast tissue (on the affected side) is necessary for women who have undergone breast conserving therapy. This substantially decreases the chance that the tumor will return in the remaining breast tissue.

In addition, chest wall radiation therapy may be recommended to women who have undergone a mastectomy, particularly if they have a large number of involved axillary lymph nodes (≥4 lymph nodes) or inflammatory breast cancer. Studies show that having a combination of surgery and radiation therapy decreases the chance that the breast cancer will return in the breast or the chest wall.

INFLAMMATORY BREAST CANCER

The treatment of inflammatory breast cancer is similar to that of other types of 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 mastectomy is usually recommended, even if there was a good response to neoadjuvant chemotherapy. Following mastectomy, radiation therapy to the chest wall and regional 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. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Breast cancer guide to diagnosis and treatment
Patient information: Lymphedema after breast cancer surgery

Professional Level Information:
An overview of treatment for locally advanced, recurrent, and metastatic breast cancer
Breast imaging: Mammography and ultrasonography
Clinical features and management of locally advanced and inflammatory breast cancer
Pathology and molecular pathogenesis of inflammatory breast cancer
Radiation techniques for locally advanced breast cancer
TNM staging classification for breast cancer
Patient information: Lymphedema after breast cancer surgery

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• 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)

[1-10]