August 01, 2013
A study led by investigators from Thomas Jefferson University's Kimmel Cancer Center has discovered molecular clues that may help physicians therapeutically target inflammatory breast cancer (IBC), a highly aggressive form of breast cancer.
Their study, reported in the June 21 online issue of Breast Cancer Research and Treatment, identified two molecules (ALK and FAK1) involved in the IBC cancer pathway. Drugs already exist that inhibit both of these two cancer-promoting proteins at the same time, which the researchers are now testing in animal preclinical studies.
"Women diagnosed with inflammatory breast cancer are in great need of therapies that are tailored to this aggressive form of breast cancer. Survival rates are much lower than for other forms of breast cancer," says the study's lead author Sandra V. Fernandez, Ph.D., Assistant Professor in the Medical Oncology Department at Jefferson.
IBC is a particularly aggressive and highly metastatic form of breast cancer characterized by very rapid onset of progression — weeks to a few months — and metastasis that spreads quickly to the brain, bones, and soft tissues. The three-year survival rate is 40 percent for IBC patients compared with 85 percent in other forms of breast cancer. Additionally, IBC patients are younger when diagnosed.
The disease is also difficult to diagnose because it appears as redness and swelling of the breast. There are no classic tumor masses.
"Because of how this cancer looks, physicians often think it is dermatitis, or inflammation, or an infection, such as mastitis. I know of many patients who were misdiagnosed from the start, and by the time they were referred to an oncologist, their cancer had progressed," says the study's senior investigator, Massimo Cristofanilli, MD, FACP, Professor of Medical Oncology and Director of the Jefferson Breast Care Center.
"We need to improve both diagnosis and treatment of this cancer, which is on the rise for reasons that are not understood," he says.
The advances reported in the study were possible because the research team developed a new animal model of IBC, derived from tumor cells from a patient with metastatic triple negative (estrogen receptor-negative, progesterone receptor-negative, Her2-negative) inflammatory breast cancer under an IRB-approved study. At the present, there are few animal models to study this particular disease.
In addition to identifying some of the pathways involved in IBC, the researchers were able to characterize the pattern of spread of the disease, which moved quickly to organs and the brain. They found that clumps of the cancer — not tumor masses — obstruct lymphatic channels in the breast, causing the swelling of breast tissues.
"This animal model is a really important tool to use to study IBC progression and metastasis, and to test potentially beneficial drugs," says Dr. Fernandez.
Researchers from the University of Texas M D Anderson Cancer Center and Fox Chase Cancer Center contributed to the research.
The study was supported by the American Airlines-Komen for the Cure Foundation Promise Grant KGO81287, NIH NCI 1R01 CA 138239, and the Inﬂammatory Breast Cancer Foundation.
The authors declare that they have no conflicts of interest.