Inflammatory Breast Cancer: All About This Rare Form

Learn more about inflammatory breast cancer (IBC) and BCRF research to improve outcomes for this type

Inflammatory breast cancer (IBC) is a rare but very aggressive subtype of the disease, accounting for one to five percent of all breast cancers diagnosed in the U.S. Inflammatory breast cancer generally occurs in women under 40, with Black women having a higher risk than white women. It also typically occurs in women with dense breasts. Further, inflammatory breast cancer is more common in obese women compared to their normal-weight counterparts. And men can have inflammatory breast cancer but are usually older at diagnosis.

The signs and symptoms of IBC differ from other breast cancers, and researchers are focused on gaining a better understanding of the disease particularly because of its fast-growing nature and prevalence in younger and Black women.

Inflammatory breast cancer is indeed an aggressive disease, but, thanks to research, survival has improved significantly with existing treatments and combinations. Read on to learn about inflammatory breast cancer and how BCRF is supporting research to improve outcomes for this form.

What is inflammatory breast cancer?

Inflammatory breast cancer occurs when cancer cells block lymph vessels in the skin of the breast. Lymph vessels are part of the lymphatic system that stretches throughout the body, passing through numerous lymph nodes and helping to filter out unwanted materials such as bacteria and damaged cells.

When a lymph vessel is blocked, inflammation develops. In inflammatory breast cancer, this causes the breast to become swollen and red or inflamed. Most inflammatory breast cancers develop from cells that line the milk ducts of the breast and then spread beyond the ducts. This subset of invasive breast cancer spreads rapidly, often to nearby lymph nodes and sometimes to distant parts of the body.

Inflammatory breast cancer symptoms

Inflammatory breast cancer is different from other breast cancers in several key ways. It often doesn’t cause a lump or show up on a mammogram, so it can be difficult to diagnose.

The symptoms of inflammatory breast cancer also differ from other breast cancers and include:

• Redness or a rash on more than one-third of the breast
• Pink, reddish-purple, or bruised breast skin
• A rapid increase in the size of a breast due to swelling with one breast appearing larger, warmer, and heavier than the other
• A breast that is tender, painful, or itchy
• Pitting or thickening of the skin that resembles an orange peel (peau d’orange)
• A flattened or discolored nipple
• Swelling of the lymph nodes under the arms or near the collarbone

Inflammatory breast cancer rashes

Rashes are typically the first symptom of inflammatory breast cancer. They may initially appear as an irritation of the skin or red bumps, or may look like bruising on one breast. Inflammatory breast cancers may also cause breast skin to appear dimpled. While rashes on the breast can develop for a variety of reasons, inflammatory breast cancer rashes tend to spread quickly.

For pictures of what an inflammatory breast cancer rash looks like, the IBC Network Foundation offers several examples here. Please note: The images may be graphic and are intended for educational purposes only. Talk to your doctor about any concerning changes on your breasts.

How is inflammatory breast cancer diagnosed?

Unlike other breast cancers, inflammatory breast cancer doesn’t form distinct lumps, which makes it difficult to diagnose through standard breast cancer imaging tests. Instead, IBC is diagnosed by a biopsy of a small sample of the affected area. A doctor might also take a punch biopsy, which is a deep sample of the breast area including all the layers of the skin. A pathologist then analyzes samples to determine if a woman has inflammatory breast cancer.  

Because it’s difficult to detect early by mammograms and other imaging techniques, inflammatory breast cancer is often diagnosed at a locally advanced stage (usually at least stage 3) because breast cancer cells have grown into the skin. For about one-third of patients at diagnosis, their IBC is already stage 4/metastatic, having spread to distant parts of the body. This can unfortunately mean that women with IBC tend to have a worse prognosis than women with other common types of breast cancer.

Inflammatory breast cancer treatment

Since inflammatory breast cancer has, by definition, reached lymph vessels and has caused changes in the skin, it’s likely already spreading, making it a challenge to treat. For stage 3 cases where the inflammatory breast cancer has not spread outside the breast or nearby lymph nodes, chemotherapy is often used first to shrink the tumor. Most women receive two different chemotherapies—anthracyclines (such as doxorubicin/Adriamycin®) and taxanes (such as paclitaxel/Taxol® or docetaxel/Taxotere®)—either together or sequentially.  

Surgery (mastectomy and lymph node dissection) is usually the next step to remove the cancer. After surgery, a doctor may prescribe more chemotherapy and then radiation therapy or may proceed with radiation therapy alone. Like other breast cancers, IBC samples are analyzed for the presence of hormone receptors and HER2 protein. The results dictate whether hormone therapy or HER2-targeted therapies are given with chemotherapy.

• Hormone receptor-positive IBCs are treated with hormone therapy after chemotherapy.
• HER2-positive IBCs are treated with the HER2-targeted drug trastuzumab (Herceptin®) alone or in combination with another HER2-targeted drug, pertuzumab (Perjeta®). Heart problems have been reported when these drugs are used in combination with anthracyclines. Therefore, doctors will give an anthracycline alone in the first round of chemotherapy followed by a second round with a taxane and trastuzumab plus or minus pertuzumab.  
• Triple-negative IBCs are treated with the immunotherapy drug pembrolizumab and chemotherapy before surgery. Generally, pembrolizumab alone is continued after surgery.
• If the patient has a BRCA mutation, has triple-negative or HER2-negative IBC, and has residual tumor after chemotherapy and surgery, she may receive the PARP inhibitor olaparib (Lynparza®) to lower her recurrence risk. This typically lasts for up to one year.

As researchers learn more about inflammatory breast cancer, more potential strategies will emerge to improve patient outcomes.

Inflammatory breast cancer survival rate

Survival rates are estimates of how likely someone will survive cancer for a specific amount of time after the initial diagnosis or start of treatment compared to those without cancer. For inflammatory breast cancer, the overall five-year relative survival rate is 40 percent in the U.S. However, several factors come into play when estimating survival rates for inflammatory breast cancer: the stage of cancer, a person’s age and general health, and how well the treatment plan works. And it’s important to note that population-level statistics like survival rates don’t always apply to individuals.

Another factor that can affect survival is whether the cancer has certain features. If the cancer has spread to the regional lymph nodes, the five-year relative survival rate is 54 percent. If the cancer has spread to a distant part of the body, the five-year relative survival rate is 19 percent. These numbers are estimates and may not reflect the most recent advancements in inflammatory breast cancer diagnosis and treatment made in the last five years. Moreover, an individual’s survival rate depends on the constellation of factors specific to them.

Inflammatory breast cancer research

BCRF is investing more than $1.5 million in inflammatory breast cancer research in 2023-24, and we support several experts on this type of breast cancer. For example:

• Dr. Naoto Ueno leads one project seeking to establish a novel therapy for inflammatory breast cancer by targeting the environment surrounding the tumor: the tumor microenvironment (TME). The protein early growth response-1 (EGR1) has been shown to be involved in many aspects of the immune response, particularly inflammation. Dr. Ueno and his team found that EGR1 can reduce the ability of immune T cells to kill cancer cells, and inhibiting EGR-1 can improve outcomes in inflammatory breast cancer. They have focused on targeting the EGFR protein in IBC using panitumumab, an anti-EGFR antibody. Studies are ongoing to identify novel molecules that degrade EGR1 and to understand how these molecules affect the growth of IBC cells, movement of immune cells to IBC tumor, and potentially improve the efficacy of immunotherapy.

• Dr. Sofia Merajver is studying how aggressive breast cancer cells like IBC cells are rewired to increase motility throughout the body or metastasize. Her team has devised potential new avenues to interfere with the proteins that mediate these cancer cells’ movement and spreading. They hope to guide therapies that prevent metastases from occurring in women diagnosed with these breast cancers. In addition, they hope to extend their results to reach underserved populations.

BCRF researchers are also investigating other forms of breast cancer, and their results may inform treatment strategies for IBC.

• Dr. Britta Weigelt focuses on a form of triple-negative breast cancer called metaplastic breast cancer which is rare but aggressive. Her team is examining the complex genetic make-up of these cancer cells to understand how they develop resistance to current treatments. They are also investigating if metaplastic breast cancer may be sensitive to a promising suite of therapies called antibody-drug conjugates, and they hope to expand the therapeutic arsenal against this and other breast cancers.

• Dr. Jenny Chang is investigating a very promising combination therapy regimen against metaplastic breast cancer. Her team has shown that this novel combination regimen could eliminate or significantly delay the growth of this form. They are also examining the interplay of obesity and fast-growing breast cancer and have recently completed a phase Ib/II trial in patients with metastatic and locally advanced disease. They found that patients with a high BMI experienced an impressive overall response rate of 86 percent to the novel therapeutic combination. Dr. Chang’s results may inform the treatment of inflammatory breast cancer and reduce the time needed to translate preclinical findings into clinical applications.

• Dr. Joshua LaBaer is seeking new drug targets to personalize treatments for aggressive breast cancers like inflammatory. His team has been using cutting-edge sequencing and gene editing technologies, and they have identified key genes and mutations that partner with different mutant p53 proteins and increase cancer-like behavior of cells. They are confirming the target genes and their mechanisms of action and hope to develop personalized treatment regimes.

In addition to these projects, research focused on developing new treatments may impact inflammatory breast cancer, as these cancers can be triple-negative, hormone- and HER2-positive or negative, research to understand and better treat each form of breast cancer benefits IBC, as well. Currently, BCRF invests more than $31 million to investigators and projects seeking to optimize existing therapies and identify new treatments and combinations.

References

Breast cancer Statistics | How common is breast cancer? (n.d.-a). American Cancer Society. https://www.cancer.net/cancer-types/breast-cancer-inflammatory/statistics

Inflammatory breast Cancer | Details, diagnosis, and signs. (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/inflammatory-breast-cancer.html

The IBC Network Foundation. (2024, June 3). The IBC Network Foundation – Inflammatory Breast Cancer. https://theibcnetwork.org/

Treating inflammatory breast cancer. (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/treatment/treatment-of-inflammatory-breast-cancer.html