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The receptors measured on the original tumour are not always the receptors of a cancer that comes back years later. On meta-analysis about a fifth of oestrogen receptor-positive primaries had become negative in their metastases, and about half had lost the progesterone receptor. It is why a returning cancer is biopsied again rather than treated from the old report.
A meta-analysis of 39 studies of paired primary tumours and distant metastases found conversion in both directions. From positive to negative the pooled rates were 22.5 percent for oestrogen receptor, 49.4 percent for progesterone receptor and 21.3 percent for HER2; from negative to positive they were 21.5 percent, 15.9 percent and 9.5 percent. The site mattered: oestrogen receptor discordance was significantly higher in central nervous system and bone metastases than in liver metastases, while progesterone receptor discordance was higher in bone and liver than in the brain. The authors' conclusion was that conversion happens often enough in the course of progression that reassessing receptor status in metastases is strongly encouraged, and that nobody has yet run the prospective study showing what treating on the new result rather than the old one does to survival (Schrijver 2018).
British practice follows that logic cautiously. NICE CG81 recommendation 1.4.1 says that for people whose breast cancer has recurred, consider reassessing hormone receptor and HER2 status if a change in receptor status will lead to a change in management. The condition in that sentence is doing real work: a biopsy of a bone or liver deposit is not a trivial procedure, and it is worth it when the answer could open or close a treatment route, which in 2026 it increasingly can, because HER2-low and ultralow scoring decides eligibility for trastuzumab deruxtecan and because expression varies between blocks of the same tumour as well as between the primary and its metastases.
Some of the apparent conversion is not the cancer changing. Immunohistochemistry has real limits at the bottom of its range, decalcified bone specimens stain badly, the cut-off for positivity moved from 10 percent to 1 percent internationally in 2010 and some countries moved later, and tumours are heterogeneous, so a single block may not represent the whole deposit. The safe reading is that the receptors are a property of the tissue tested on the day it was tested, not a permanent label on the patient.
Shares How ER and PR are scored on a breast report (Allred score, H score, and why PR is not a UK core item), HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, Hormone receptor status (ER / PR), HER2-positive (IHC 3+ or ISH-amplified).
Shares ER and PR negative under 1 percent (the triple-negative threshold, and ER-low), HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow.
Shares HR-positive metastatic breast cancer after CDK4/6 inhibitors, HER2-positive breast cancer, Breast cancer (all types), HR-positive / HER2-negative breast cancer.
Shares HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, HER2-low and HER2-ultralow, HER2-positive breast cancer, Breast cancer (all types).
Shares HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, Breast cancer (all types), Triple-negative breast cancer (TNBC).
Shares HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, HR-positive metastatic breast cancer after CDK4/6 inhibitors, Triple-negative breast cancer (TNBC).
Shares HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, Breast cancer (all types), HR-positive / HER2-negative breast cancer.
Shares HER2-low and HER2-ultralow metastatic breast cancer, HER2-positive breast cancer, HR-positive / HER2-negative breast cancer.