Inflammatory Breast Cancer: A Disease That Continues to Puzzle

One to 5% of all diagnosed breast cancers in the United States are inflammatory breast cancer, a very aggressive, heterogeneous form in which cancer cells block lymph vessels, causing the breast to become swollen and red.¹ A change in breast size, inverted nipples, and warmth to the touch may also result. Symptoms progress rapidly, often within weeks or months.

Diagnosing inflammatory breast cancer can be complicated because symptoms often mimic mastitis and mammography fails to detect the tumors.¹ Biopsy is the only reliable method of diagnosing inflammatory breast cancer.

Most inflammatory breast cancers are invasive ductal carcinomas and are typically diagnosed at stage 3 or 4. Among patients diagnosed with grade 1 or 2 cancer, 77% survive at least 2 years after diagnosis compared with 65% for those with grade 3 cancer, according to the National Cancer Institute (NCI).¹

Since detection is so elusive and the cancer is so aggressive, researchers are eager to identify biomarkers for this disease. What clinicians do know is that inflammatory breast cancer tends to occur in younger women, particularly in obese women, and is frequently hormone receptor-negative, so hormone-based therapies such as tamoxifen are usually not effective.¹

WHAT DO THE DATA SHOW?

As scientists learn more about cancer, questions about inflammatory breast cancer arise. Why does it progress so quickly? Why is it so difficult to diagnose? Are there any molecular pathways presenting vulnerabilities for interventions? What is the pathogenesis of inflammatory breast cancer? Are viruses the cause? Behaviors?

The recent American Society of Clinical Oncology (ASCO) Annual Conference held in Chicago, Illinois in June 2012 offered some insights. An international team of researchers, led by the Morgan Welch Inflammatory Breast Cancer Program and Clinic at University of Texas MD Anderson Cancer Center in Houston, Texas, examined data to evaluate molecular connections between inflammatory breast cancer and triple-negative inflammatory breast cancer, another form of breast cancer that also has a poor prognosis. They found that triple-negative inflammatory breast cancer and triple-negative noninflammatory breast cancer shared the same subtypes and clinical outcomes, although there was no significant association between triple-negative breast cancer subtype and inflammatory breast cancer status.² In 2010, MD Anderson researchers also reported that the rate of BRCA mutations was not different between patients with inflammatory and noninflammatory breast cancer.³

The quest for molecular biomarkers was also pursued by researchers at George Washington University School of Public Health and Health Services in Washington, D.C., who compared the molecular features of inflammatory breast cancer to locally advanced breast cancer to determine potential pathways. The team evaluated national registry data involving 100 cases of inflammatory breast cancer and 107 cases of noninflammatory breast cancer that were diagnosed as locally advanced using the National Cancer Institute (NCI) Cooperative Breast Cancer Tissue Resource. Levels of E-cadherin, a calcium-dependent cell adhesion molecule, were higher in classic inflammatory breast cancer cases compared with noninflammatory cases. In contrast, lymphatic vessel density (LVD) and the protein vascular endothelial growth factor D (VEGF-D), which is often seen at high levels in patients with angiosarcoma, were higher among patients with locally advanced breast cancer. The full study will be published in the journal Clinical Breast Cancer.⁴