The Clinical and Biological Significance of ER “Low-Positive” Breast Cancer

Estrogen receptor (ER) status in breast cancer (BC) is determined using immunohistochemical nuclear expression. Currently, tumors with 1% or more positive cells are defined as ER-positive. BC, with 1%-9% expression (ER-low-positive), is a clinically and biologically unique subgroup. In this episode of Mod Path CHAT, Dr. Emad Rakha discusses his team’s study on the subject.

A large BC cohort (8171) was investigated and categorized into 3 groups: ER low-positive (1%-9%), ER-positive (≥10%), and ER-negative (<1%). A subset of ER low-positive cases was further evaluated using IHC, RNAscope, and RT-qPCR.

ER low-positive tumors constituted <% of BC cases examined and showed significant clinicopathological similarity to ER-negative tumors. Further validation of ER status revealed that 45% of these tumors were ER-negative with repeated IHC staining and confirmed by RNAscope and RT-qPCR. BCs with 10% ER behaved similarly to ER-positive BCs.

The authors recommend repeat testing of BC showing 1%-9% ER expression and using a cutoff ≥10% expression to define ER positivity to help better inform treatment decisions.