Inflammatory Breast Cancer

The cancer is called IBC because its symptoms appear as though the breast is inflamed or infected. Unlike other types of breast cancer that cause a lump in the breast, IBC does not cause any mass or lump.

Inflammatory breast cancer (IBC) is a rare type of breast cancer. The cancer is called IBC because its symptoms appear as though the breast is inflamed or infected. Unlike other types of breast cancer that cause a lump in the breast, IBC does not cause any mass or lump.

Inflammatory breast cancer is a rare and aggressive form of breast cancer. It is typically a very aggressive disease and is called "inflammatory" because the cancer cells block the lymphatic vessels, resulting in changes in the breast (swelling and redness) that make the breast appear to be inflamed, resembling an infection in the breast (mastitis). Over 240,000 people in the United States are diagnosed with breast cancer each year; inflammatory breast cancers make up only 1%-5% of breast cancers.

The causes and risk factors for inflammatory breast cancer are the same as those for breast cancer in general. Certain genetic mutations and a family history of breast cancer are two of the known risk factors. However, inflammatory breast cancer tends to affect certain women more frequently than others (See "How is inflammatory breast cancer different from other breast cancers?").

The characteristic inflammatory symptoms in IBC are due to the cancer cells blocking the lymph channels in the breast. Having any of these symptoms does not mean that you have IBC. Because of the aggressive nature of the disease, it is important to consult your doctor right away.

Inflammatory breast cancer (IBC) is a rare but rapidly growing cancer that gives rise to several signs and symptoms, mostly within a span of three to six months. One of the first signs is most likely to be visible swelling (edema) of the skin of the breast and/or redness of the breast (which covers more than 30 percent of the breast). Other signs and symptoms include:

• Rash or redness involving more than one-third of the breast
• Orange peel appearance of the breast skin (the breast skin appears pitted and thickened like an orange peel)
• Pitting, dimpling, or bruising of the skin of the breast
• Nipple retraction or inversion on the affected side (the nipple appears to point inward)
• Breast asymmetry (the affected breast looks larger and feels heavier because of swelling)
• The affected breast is warm to touch
• Breast pain and tenderness
• Itching over the breast
• Swollen or enlarged lymph nodes under the arms or near the collarbone
• Heaviness
• A rapid increase in size of the breast

Sometimes, a mass or lump can be felt in the breast, but commonly no mass can be felt. Enlarged lymph nodes may be present in the underarm or near the collarbone.

While the symptoms of inflammation in the breast are characteristic of inflammatory breast cancer, they can also arise due to infections and other conditions such as mastitis, so any unusual symptoms or changes in the breasts should be evaluated by a medical professional.

Inflammatory breast cancer is typically an aggressive form of cancer that spreads rapidly. Because it involves the lymphatic system and the cancer cells have invaded the lymph vessels at the time of diagnosis, it is already at a more advanced stage (or extent of spread) than many breast cancers when it is discovered. This type of breast cancer is usually found in women at a younger age than most breast cancers; the median age for diagnosis of inflammatory breast cancer is 57 years compared to 62 years for all breast cancers. Very few cases of inflammatory breast cancer have been described in men.

Inflammatory breast cancer is more common in African American women than in Caucasian women and is diagnosed at an earlier average age. In African American women, the median age at diagnosis of inflammatory breast cancer is 54 years, compared with 58 years for Caucasian women. Inflammatory breast cancer is also more common in obese women than in women with normal body weight.

Inflammatory breast cancers often are hormone receptor-negative, meaning that their cells do not have receptors for estrogen or progesterone on the surface. This means that therapies (such as tamoxifen) that target estrogen-driven tumor growth are unlikely to be effective.

Mammography and imaging tests

Screening mammography has made it possible to detect many breast cancers before they produce any signs or symptoms. However, inflammatory breast cancer produces symptoms, so in the case of this cancer, the mammogram may be used to evaluate the breast when symptoms are present or to determine the location for a breast biopsy. Due to the rapid spread of cancer, this cancer is sometimes found during routine mammogram exams. Other imaging tests, including MRI, ultrasound, PET scans, and CT scans may be used to evaluate the breast if inflammatory breast cancer is suspected. A bone scan to look for spread (metastasis) to the bones may also be performed if a diagnosis of inflammatory breast cancer is confirmed.

Definitive diagnosis

Even if imaging tests show an abnormality or are suspicious of breast cancer, a definitive diagnosis requires a tissue sample or biopsy. A biopsy may be taken of a small area of the abnormality (an incisional biopsy), or the entire abnormal area may be removed at the time of biopsy (excisional biopsy). A skin biopsy might also be taken at the same time as the breast biopsy. A biopsy allows the pathologist (a physician with special training in the diagnosis of diseases based on tissue samples) to determine if cancer is present, and if so, what type of cancer. Biopsy also provides a tissue sample for further tests that are done (see below) to determine the best type of treatment. If a mass is not identified in the breast, a skin biopsy can sometimes be used to establish the diagnosis of inflammatory breast cancer. The diagnosis of inflammatory breast cancer can be challenging.

The diagnostic guidelines for inflammatory breast cancer require that the following factors are present:

• Rapid onset of erythema (redness), edema (swelling), and a peau d'orange appearance and/or abnormal breast warmth, with or without a lump that can be felt
• These symptoms have been present for less than six months.
• The redness covers at least one-third of the breast.
• A biopsy from the affected breast reveals invasive cancer.

Specialized testing on breast cancer samples

Certain laboratory tests are typically performed on all breast cancer tumor samples to help determine the optimum treatment. These include:

• Hormone receptor status: Breast cancer tissue is tested for the presence of receptors for the hormones estrogen (estrogen receptor or ER) and progesterone (progesterone receptor or PR). If these receptors are present, the tumor is referred to as hormone receptor-positive. This means that hormone-directed therapies may be effective in stopping tumor growth.
• HER2: Another test performed on breast cancer tissue measures the overexpression of a protein called HER2. If a tumor is HER2-positive (HER-2+), drugs that target this specific protein may be given. About 15% of people with breast cancer have so-called triple-negative breast cancers. This means that they do not express any of these tumor markers (ER, PR, or HER2). As mentioned before, inflammatory breast cancers often do not express the hormone receptors ER and PR.
• Other laboratory tests may be useful for some types of tumors to help determine the prognosis and treatment plan. These include, for example, studies of gene expression in a particular tumor or tests to look for the presence of circulating tumor DNA.

Staging of cancer refers to the determination of how far the tumor has spread at the time of diagnosis. Staging is determined by a variety of methods including results from surgical procedures, lymph node biopsy, and imaging tests. Staging is important because it aids in developing a treatment plan.

• Cancer in situ (DCIS) is referred to as stage 0 because the tumor cells are located in the breast ducts and have not invaded the surrounding tissue.
• Invasive breast cancers are staged along a scale of I to IV, with stage I being the earliest stage and stage IV representing tumors that have metastasized to other parts of the body like the bones, lungs, or brain.
• Because inflammatory breast cancers have already spread into the lymphatic vessels and cause symptoms related to this presence in the lymphatic system, all inflammatory breast cancers are stage III or stage IV at diagnosis.

Breast cancer treatment for inflammatory breast cancer typically involves chemotherapy, surgery, and radiation. In some cases, additional targeted therapies are given. The term neoadjuvant refers to therapies that are given before surgery, while adjuvant refers to treatments given after surgery.

• Neoadjuvant chemotherapy refers to chemotherapy medications that are given before surgery to shrink the tumor. In patients with inflammatory breast cancer, this is often done so that the tumor is smaller and easier to remove during the surgery. A typical course of neoadjuvant chemotherapy would involve at least six cycles of chemotherapy over four to six months. The chemotherapy regiment usually involves taxane and anthracycline drugs.
• If the tumor cells express the HER2 protein (see above), targeted therapies such as trastuzumab can also be given as a neoadjuvant (before surgery) therapy and continued after surgery (adjuvant therapy).
  • Inflammatory breast cancers are often positive for the HER2 protein, so the tumors can be responsive to treatments that target this protein. In addition to trastuzumab, other drugs that target HER2 activity are available.
• It is less common for inflammatory breast cancers to express hormone (ER or PR) receptors, but if the tumor is hormone receptor-positive, hormone therapies that target estrogen can be effective.
  • Tamoxifen is a drug that interferes with the activity of estrogen in the body and is a common hormone therapy drug. It can be given to both premenopausal and postmenopausal women.
  • In postmenopausal women, drugs known as aromatase inhibitors are also used as hormone therapy. Examples of aromatase inhibitors include anastrozole, letrozole, and exemestane.
• Surgery for inflammatory breast cancer usually involves a modified radical mastectomy with the removal of lymph nodes, since the tumor has spread into the lymphatic system. Following surgery, radiation therapy is typically administered to the chest wall. This treatment uses radiation to destroy the remaining cancer cells. The most common type of radiation therapy is given in a clinic, usually five days a week for several weeks.
• Adjuvant therapy after surgery can include hormone therapy, chemotherapy, targeted therapy, or a combination of these methods described above.

Clinical trials, in which new drugs, new therapies, or a combination of drugs and therapies are tested, may be available for some patients with inflammatory breast cancer and offer an additional treatment option. Anyone interested in taking part in a clinical trial should discuss this possibility doctor. Information about clinical trials is available from the National Cancer Institute's Cancer Information Service at 1-800-4-CANCER and at http://www.cancer.gov/clinicaltrials.

The prognosis, or survival rates, for breast cancer, depend upon the extent to which cancer has spread and the treatment received. Because inflammatory breast cancer is diagnosed when cancer has already spread to the lymphatic system, survival rates for this type of breast cancer are not as favorable as for other types of breast cancer. Still, it is important to remember that statistics about breast cancer are based on studies of patients who were diagnosed years ago, and since therapies are constantly improving, current survival rates may be even higher.

In terms of inflammatory breast cancer, some factors are associated with a better prognosis (more favorable outcome):

• Stage: Stage III tumors have a better prognosis than stage IV tumors.
• Grade: Higher-grade tumors (grade refers to the extent to which the cells resemble normal breast cells under a microscope; the higher the grade, the more abnormal the cells) tend to have a worse prognosis.
• Studies have shown that African American women with inflammatory breast cancer have a worse prognosis than women of other racial groups.
• Inflammatory breast cancers that are estrogen receptor-positive tend to have a better prognosis than those that are estrogen receptor-negative.
• Women who undergo multimodal therapy (a combination of chemotherapy, surgery, and radiation therapy) have a better prognosis than women who do not have this type of therapy.

There is no guaranteed way to prevent any type of breast cancer. Modifying the risk factors that can be altered (increase exercise, keep good body weight, etc.) can help in decreasing the risk of getting breast and other cancers. Some women who are at increased risk of breast cancer may be given medications to decrease their risk or even undergo preventive mastectomy if they are at very high risk for breast cancer. None of these measures, though, are 100% effective in preventing breast cancer.