ER, PR, and HER2: Why Re-check for Metastases?

Background: Estrogen receptor status, progesterone receptor status, and HER 2 status are essential to classifying breast cancer into major subtypes requiring varying treatments: HER2-enriched; hormone receptor positive; and triple negative breast cancers. The status or ER, PR, and HER2 are checked for the primary (original cancer in the breast), but should we re-check the metastasis? Do ER, PR, and HER2 change?

Metastatic breast carcinoma; pleura-Estrogen r...
Metastatic breast carcinoma; pleura-Estrogen receptor (Photo credit: Pulmonary Pathology)

What the researchers did: Receptor statuses wre assed by immunohistochemistry with a cutoof of ER or PR 10% positive. HER2 was considered positive if IHC was 3+ or FISH amplification ratio >2.

Results: Discordance (the status changed) in one or more receptors between primary breast cancer and metastatic disease was found in 42% of patients. A switch in receptor status was found for ER in 17% of tumors, PR in 29% of tumors, and HER2 in 4%. Exposure to anthracycline chemotherapy (e.g. doxorubicin or Adriamycin) was statistically associated with switches in ER status. Discordance for ER was almost statistically significant for metastases to the liver, and PR discordance was statistically significant for liver spread.

My take: This study confirms that discordance in ER and PR expression between the primary breast tumor and the corresponding metastatic lesion is high, whereas HER2 remains relatively constant. These results were obtained in a selected group of patients, so additional studies are needed. Still, it is probably wise to biopsy the first site of metastasis to re-check the receptors. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

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Reference: The Oncologist 2013:18:667-674 (

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Harvard AB Yale MD UPenn Radiation Oncology Radiation Oncologist, Seattle area

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