Diagnosis
Diagnosing HR+, HER2– BC1-3
During the initial diagnostic workup for BC, imaging, biopsy and pathology tests are used to determine:
- Tumour grade
- Stage
- Tumour size
- Lymph node involvement
- Presence of metastases
- Biomarker expression such as ER, PR and HER2.
Genomic testing may also be performed to assess the risk of recurrence and to identify actionable biomarkers.
Key biomarker testing of primary tumour (ESMO guidelines)2,4
Testing of the primary tumour follows ESMO guidelines and focuses on key biomarkers, particularly HR and HER2 status.
These are classified as follows:
HR status
- HR+: 1–100% of tumour nuclei positive for ER or PR
- HR–: <1% or 0% of tumour nuclei are immunoreactive
HER2 status4
- HER2+: Immunohistochemistry (IHC) 3+, or IHC 2+ with in situ hybridisation (ISH) amplification
- HER2–: IHC 0 or 1+, or IHC 2+ without ISH amplification
- HER2-low: IHC 1+ or IHC 2+ without ISH amplification.
These biomarker assessments are essential for guiding diagnosis and treatment decisions.2
mBC testing guidelines
Upon diagnosis of mBC (newly diagnosed or metastatic recurrence [with re-biopsy]), clinical guidelines recommend (re)assessment of ER/PR and HER2 status, as well as genomic testing for actionable biomarkers in the mBC setting (e.g. PIK3CA mutations, ESR1 mutations).2,5
Note: genomic alterations shown are ESCAT level I only and not intended as a comprehensive list.
* In patients with disease progression after aromatase inhibitor (AI) treatment.
ESCAT (ESMO Scale of Clinical Actionability for molecular Targets) evidence tiers:6
I: Alteration-drug match is associated with improved outcome in clinical trials; IA: prospective, randomised clinical trials show the alteration-drug match in a specific tumour type results in a clinically meaningful improvement of a survival endpoint.
II: Alteration-drug match is associated with antitumour activity, but magnitude of benefit is unknown.
References
- https://www.cancer.gov/types/breast/diagnosis#tests-to-stage-breast-cancer (accessed March 2026);
- Gennari A, et al. Ann Oncol 2021; 32:1475–1495 {ESMO Metastatic Breast Cancer Living Guideline, v1.2 April 2025};
- https://www.cancer.gov/types/breast/stages (accessed March 2026);
- Tarantino P, et al. Ann Oncol 2023; 34:645–659;
- Mosele MF, et al. Ann Oncol 2024; 35:588–606;
- Mateo J, et al. Ann Oncol 2018; 29:1895–1902.
