Seeing the Forest for the Trees with Prognostic Factor Testing
Prognostic factor testing is critical for directing proper therapy in individuals diagnosed with breast cancer. We have known for quite some time that there are several different types of breast cancer. Some tumors grow slow. Some tumors grow fast. Some tumors rapidly spread to other body parts and others rarely spread. These different types of breast cancer have different clinical courses and necessitate different types of treatment.
Many different factors go into deciding what treatment options are best for individuals diagnosed with breast cancer, including clinical factors such as patient age and patient lifestyle, as well as several pathologic factors such as tumor stage, histologic grade, and prognostic factor status.
Prognostic factors are molecular (protein and/or DNA) markers that are either present or absent within the tumor cells. They are called “prognostic factors” because their presence or absence correlates with tumor recurrence and overall patient survival. Furthermore, some of the prognostic factors for breast cancer are also therapeutic, meaning that their presence or absence determines what kind of therapy will be available to the patient.
The most critical prognostic (and therapeutic) factors for breast cancer are Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor-2 (HER-2). Approximately 70 – 80% of breast cancers are positive for ER and/or PR, and 15 – 20% of breast cancers are positive for HER-2. Very rarely are tumors positive for all three factors. Approximately 10 – 15% of breast cancers are “triple negative,” meaning that they are negative for ER, PR, and HER-2.
ER and PR are both nuclear hormone receptors that respond to the female hormones estrogen and progesterone. Tumor cells that are positive for ER and/or PR are dependent upon these female hormones for cell growth. There are medications available that can interfere with and block this cell growth-signaling pathway, including Tamoxifen and a relatively new class of drugs called aromatase inhibitors. These medications, in hormone receptor-positive breast cancers, greatly reduce the chance of disease recurrence and increase patient overall survival.
Similarly, HER-2 is also a growth factor receptor but is expressed on the tumor cell surface membrane. The presence of HER-2 on the cell surface drives the growth of HER-2 positive breast cancers. Anti-HER-2 medications (Trastuzumab and Lapatinib) are available that bind to and inhibit the cell growth-signalling function of HER-2, thereby greatly reducing the chance of disease recurrence and increasing patient overall survival.
With rare exception, every breast cancer at the time of diagnosis needs to be tested for these three markers. Because the availability of certain types of therapy for patients with breast cancer is directly dependent upon the prognostic factor testing results, the College of American Pathologists (CAP) and American Society of Clinical Oncologists (ASCO) have teamed up and established strict guidelines for the testing of these prognostic markers in breast cancer. These guidelines exist to ensure precise and reliable results. Prognostic marker testing should only be done in fully accredited laboratories that adhere to these guidelines and have ongoing quality assurance programs.
story by BRIAN J. YODER, DO, PH.D
BIO: Dr. Brian J. Yoder is director of GynoPath at MicroPath Laboratories in Lakeland and a Polk County Medical Association member. He has authored other articles in The Breast Journal, The Journal of Urology, and American Journal of Surgical Pathology. Dr. Yoder is also a staff Pathologist at Lakeland Regional Medical Center and the laboratory medical director of Clark and Daughtrey.