Biomarker Testing: ER, PR and Her2

Written by: Ashley Cimino-Mathews MD and Gang Zheng MD PhD

One important aspect of the role of Pathology in the evaluation of breast cancer is biomarker testing, specifically the accurate assessment of the estrogen receptor (ER), progesterone receptor (PR), and Her2 status of a patient's breast cancer. Biomarkers can be prognostic, predictive, or both. Prognostic biomarkers are independent measures of prognosis such that the presence or absence of the biomarker is associated with a patient's overall clinical outcome (i.e., risk of recurrence and mortality). Predictive biomarkers, in contrast, predict whether or not a patient will respond to a given therapy.

The expression of the hormone receptors ER and PR in a patient's breast cancer is an example of a weak prognostic but strong predictive biomarker. If a patient's tumor expresses ER and/or PR, as seen in approximately 70% of invasive breast cancers, we can predict that this patient will likely benefit from endocrine therapy such as tamoxifen. The overexpression of the oncogene Her2 in a patient's breast cancer, as seen in approximately 15-20% of invasive breast cancers, is an example of both a prognostic and predictive biomarker. Her2 expression is associated with a diminished prognosis (e.g., higher risk of recurrence), however, it also predicts that a patient will more likely benefit from anthracycline and taxane-based chemotherapies and directed therapies that target Her2 (trastuzamab), but not to endocrine-based therapies.

Many factors influence the accuracy of detection of ER, PR, and Her2 in the laboratory. These include pre-analytical factors (including prompt fixation of appropriate duration), analytic factors (including utilization of validated procedures with ongoing proficiency testing), and post-analytic factors (including appropriate reporting). Importantly, the results of these tests alone are the key determinants of what treatment is selected. The goal is to provide the right treatment to the right patient. The role of the pathologist is to accurately assess these biomarkers, which as indicated above is quite challenging and involved. The role of the oncologist is to treat the patient with one of several standardized therapies (endocrine therapy for ER/PR positive carcinomas, Trastuzumab for Her-2 positive carcinomas).

A Summary of the Key Points of Biomarker Testing:

Special studies to determine the ER/PR and Her2 status of an invasive breast carcinoma