# HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease)

Source: https://onco.cc/terms/her2-low-and-trop2-adc-eligibility-tnbc/  
OnCo record `her2-low-and-trop2-adc-eligibility-tnbc` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Two antibody-drug conjugates reach triple-negative breast cancer by different rules. Trastuzumab deruxtecan needs the tumour to show a little HER2 (a score of 1+, or 2+ without gene amplification), so the pathologist's call between 0 and 1+ matters. Sacituzumab govitecan targets TROP2, which almost all breast cancers carry, and is given without any test.

## Summary

HER2 scoring follows the ASCO/CAP algorithm: immunohistochemistry 0, 1+, 2+ (weak to moderate complete membrane staining in more than 10 percent of cells, reflexed to in situ hybridisation) or 3+, with the 2018 focused update handling the uncommon dual-probe ISH groups (Wolff 2018). HER2-low means 1+ or 2+ without amplification. DESTINY-Breast04 randomised 557 patients with HER2-low metastatic breast cancer after one or two lines of chemotherapy to trastuzumab deruxtecan or physician's choice chemotherapy; 494 (88.7 percent) had hormone receptor-positive and 63 (11.3 percent) hormone receptor-negative disease; among all patients median progression-free survival was 9.9 against 5.1 months (hazard ratio 0.50) and overall survival 23.4 against 16.8 months (0.64), with drug-related interstitial lung disease or pneumonitis in 12.1 percent and grade 5 events in 0.8 percent (Modi 2022). The 2023 ASCO-CAP update affirmed the 2018 testing recommendations, declined to create new HER2-low or HER2-ultralow result categories because IHC 0 tumours were excluded from the trial and no biological threshold at 0 versus 1+ is established, but added a reporting comment and best-practice steps to distinguish 0 from 1+ now that the distinction decides eligibility (Wolff 2023). About a third of triple-negative tumours are HER2-low: 36.6 percent of triple-negative cases among 3,689 HER2-negative breast cancers (Schettini 2021), 34.0 percent of 1,162 hormone receptor-negative tumours in four German neoadjuvant trials (Denkert 2021) and 24.0 percent of 367 chemotherapy-naive French cases (Boissiere-Michot 2026); the molecular table on the parent page carries each cohort and the biomarker readouts carry the label thresholds. Sacituzumab govitecan is an antibody to TROP2, expressed in the majority of breast cancers, coupled to SN-38; in ASCENT (468 patients without brain metastases, all previously treated with taxanes) it gave median progression-free survival of 5.6 against 1.7 months and overall survival of 12.1 against 6.7 months versus single-agent chemotherapy, with no TROP2 test required for entry (Bardia 2021); NICE recommends it after two or more systemic therapies (TA819, August 2022), and the first-line rows on the parent page record the later ASCENT-03 and ASCENT-04 approvals. The open question on the parent page, whether a second TOP1-payload ADC works after the first, applies to both drugs.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: HER2-low TNBC; HER2 0 versus 1+; T-DXd eligibility in triple-negative breast cancer; Sacituzumab govitecan eligibility; TROP2 testing not required
- Tags: breast; tnbc

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Trastuzumab_deruxtecan
- Wolff, J Clin Oncol 2018: ASCO/CAP HER2 testing guideline focused update: https://doi.org/10.1200/jco.2018.77.8738
- Wolff, J Clin Oncol 2023: ASCO-CAP HER2 testing update (IHC 0 versus 1+ after DESTINY-Breast04): https://doi.org/10.1200/jco.22.02864
- Modi, N Engl J Med 2022: DESTINY-Breast04, trastuzumab deruxtecan in HER2-low advanced breast cancer: https://doi.org/10.1056/nejmoa2203690
- Bardia, N Engl J Med 2021: ASCENT, sacituzumab govitecan in metastatic triple-negative breast cancer: https://doi.org/10.1056/nejmoa2028485
- NICE TA819: sacituzumab govitecan for unresectable triple-negative advanced breast cancer after 2 or more therapies (August 2022): https://www.nice.org.uk/guidance/ta819

## Connected records

- cancers: [HER2-low and HER2-ultralow metastatic breast cancer](https://onco.cc/cancers/her2-low-metastatic-breast-cancer/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [HER2](https://onco.cc/targets/her2/), [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [ER and PR negative under 1 percent (the triple-negative threshold, and ER-low)](https://onco.cc/terms/er-pr-negative-threshold/), [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/)
- trials: [ASCENT](https://onco.cc/trials/ascent/), [DESTINY-Breast04](https://onco.cc/trials/destiny-breast04/)

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