Mission In Action


This month, our focus is on the work of Edith P. Mitchell, MD, FACP, Kimmel Cancer Center at Thomas Jefferson University Hospital, which has led to breakthroughs in understanding and empowering medical professionals against the very aggressive breast cancer subtype, Triple-Negative. Supported with a $7+ million research grant from Susan G. Komen for the Cure, Dr. Mitchell's progress represents your "Komen dollars" in action around the world, as 25% of net proceeds generated by the Komen Philadelphia Affiliate supports the Susan G. Komen for the Cure Grant Program.

 


April Focus: Understanding Triple-Negative Breast Cancer

By Brigadier General Edith Peterson Mitchell, MD, FACP, Kimmel Cancer Center at Thomas Jefferson University Hospital, Clinical Professor of Medicine and Medical Oncology/Program Leader in Gastrointestinal Oncology

 

It is estimated that during 2009, approximately 192,370 new cases of invasive breast cancer were diagnosed and 40,170 women died of the disease in the United States.  Approximately, ten to twenty percent of these cancers were of the triple negative subtype. 

 

Triple-negative breast cancer refers to a specific subtype of breast cancer that has specific histopathologic features. The cancer cells lack expression of the estrogen and progesterone receptors (ER/PR) and HER2 protein. In triple negative breast cancer, neither of these receptors is found and thus the name "Triple-negative".

 

The triple-negative subtype of breast cancer is characterized by a distinct clinical pattern that has a more aggressive behavior and metastases pattern, resulting is an overall poorer prognosis. Triple-negative cancers tend to have more rapid growth, spread more quickly, and have a higher risk of recurrence after initial successful treatment. In general, triple-negative breast cancers tend to develop at a younger age, have a larger tumor size, higher grade tumors, and have increased spread to lymph nodes. They are more prevalent in women of African American descent.

 

The molecular profile and phenotype of triple-negative breast cancers is frequently useful in the laboratory evaluation. Most (but not all) triple negative breast cancers have features of the basal-like molecular phenotype, which is characteristic. There is a higher incidence of other molecular markers, including p53, epidermal growth factor receptor and c-Kit, basal-like cytokeratins and P-cadherin. It has been observed that the majority of BRCA1-associated cancers are triple-negative.

 

Attempts to define risk factors associated with the development of triple negative breast cancer suggest that these cancers tend to occur more frequently in women who have onset of menses at a younger age, younger age at first pregnancy, have a shorter duration of breast feeding, and who have a higher body mass index with abdominal obesity.

 

Because triple-negative breast cancer cells do not have ER/PR receptors, hormonal therapies that are used to treat cancers positive for these receptors are not effective. Moreover, drugs that target the HER2 protein lack effectiveness. However, triple-negative breast cancers may respond to chemotherapy, which can be very useful in some cases.

 

While these tumors may respond to chemotherapy, resistance often develops and tumors frequently recur and grow rapidly after initial treatment.  Medications that specifically target triple-negative breast cancer treatment are not yet available. Targeted therapies such as those that inhibit epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and poly (ADP-ribose) polymerase (PARP) inhibitors are currently in clinical trials. It is imperative that research continues with efforts focused on prevention strategies, earlier diagnosis, and development of new treatment approaches.