# ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)

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## TL;DR

A breast cancer counts as oestrogen receptor negative when fewer than 1 in 100 of its cells stain for the receptor, and the same rule applies to progesterone receptor. Tumours with 1 to 10 percent staining are labelled ER low positive, but they behave like triple-negative cancers and in some countries are treated as such.

## Summary

The ASCO/CAP guideline recommends ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting endocrine therapy benefit: samples with 1 to 100 percent of tumour nuclei positive are ER positive; fewer than 1 percent or 0 percent is ER negative; and because data on endocrine benefit for 1 to 10 percent staining are limited, those samples are reported in a new category, ER Low Positive, with a recommended comment, laboratory standard operating procedures for low or absent staining, and the status of controls reported for 0 to 10 percent cases; the same principles apply to PR, which is used mainly for prognosis in ER-positive disease (Allison 2020). NICE NG101 asks for ER, PR and HER2 to be assessed together at diagnosis, ER by standardised quality-assured immunohistochemistry reported quantitatively, and defines triple-negative as each scored negative under local multidisciplinary team guidelines (NG101 1.3 and the terms section). The ER-low band behaves like triple-negative disease: in a US registry of 516 stage I to III HER2-negative patients with ER and PR of 10 percent or less, the 12.6 percent with 1 to 10 percent staining matched the rest for germline BRCA prevalence, chemotherapy use, pathological complete response (51.3 against 49.2 percent) and three-year recurrence-free (82.4 against 82.5 percent) and overall survival (Yoder 2022); in 406 Italian patients ER 1 to 9 percent tumours had the same five-year relapse-free (73.1 against 74.0 percent) and overall survival (76.7 against 82.3 percent) and pathological complete response (44 against 38 percent) as ER-negative tumours (Dieci 2021); and Sweden kept a 10 percent threshold when international guidelines dropped to 1 percent in 2010, treating ER 1 to 9 percent HER2-negative tumours as triple-negative, with 9.9 percent of 5,655 tumours in 2008 to 2020 in that band and no survival difference from ER-zero disease (Acs 2024). The practical consequence is that ER-low patients are often excluded from triple-negative trials of immunotherapy and ADCs, so evidence for those drugs in the band is thin (Yoder 2022).

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: ER-negative under 1 percent; ER Low Positive; ER-low breast cancer; ER 1 to 10 percent; Hormone receptor-negative threshold; PR-negative
- Tags: breast; tnbc

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Estrogen_receptor_test
- Allison, J Clin Oncol 2020: ASCO/CAP guideline update on ER and PR testing (1 percent threshold, ER Low Positive): https://doi.org/10.1200/jco.19.02309
- NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8): https://www.nice.org.uk/guidance/ng101/chapter/Recommendations
- Yoder, NPJ Breast Cancer 2022: low versus negative ER/PR in HER2-negative breast cancer: https://doi.org/10.1038/s41523-022-00448-4
- Dieci, NPJ Breast Cancer 2021: ER levels and outcome in non-metastatic triple-negative breast cancer: https://doi.org/10.1038/s41523-021-00308-7
- Acs, Lancet Reg Health Eur 2024: ER-zero and ER-low HER2-negative breast cancer treated as triple-negative, Swedish cohort: https://doi.org/10.1016/j.lanepe.2024.100886

## Connected records

- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- terms: [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)](https://onco.cc/terms/her2-low-and-trop2-adc-eligibility-tnbc/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)

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