HER2-low and HER2-ultralow metastatic breast cancer: the decisions you may face

Cancer page →Second-opinion finder →

4 treatment settings, 1 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Second line

Hormone receptor-positive, after endocrine therapy, chemotherapy-naive

One path named

Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).

The path, in plain words

Trastuzumab deruxtecanApprovedADC

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

Also referenced:HER2-low and HER2-ultralow

The evidence behind it

DESTINY-Breast06 Phase 3 NCT04494425 2024866 peopleevidence 89
Tests Trastuzumab deruxtecan
HR+ HER2-low/ultralow breast cancer after endocrine therapy, chemotherapy-naive: T-DXd vs chemotherapy
PFS HR 0.62.
Progression-free survival, HER2-low (BICR) (months): Trastuzumab deruxtecan 13.2 (n=359) vs Chemotherapy (TPC) 8.1 (n=354) · HR 0.62 · source

The main trade-offs on record

Trastuzumab deruxtecan all recorded rates →

Side effect	Any grade	Grade 3+
Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	18%
Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	6%

Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision

Is Trastuzumab deruxtecan the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
Why: A single standard does not mean a single choice; timing and trials are decisions too.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in DESTINY-Breast06, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
For my situation (hormone receptor-positive, after endocrine therapy, chemotherapy-naive), which of the standard options do you recommend and why?
Why: Guideline options include: Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).
Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of DESTINY-Breast06 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Second line

After one or two lines of chemotherapy

One path named

Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).

The path, in plain words

Trastuzumab deruxtecanApprovedADC

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

Also referenced:HER2-low and HER2-ultralow

The evidence behind it

DESTINY-Breast04 Phase 3 NCT03734029 2022557 peopleevidence 88
Tests Trastuzumab deruxtecan
HER2-low metastatic breast cancer after chemotherapy: T-DXd vs chemotherapy
OS HR 0.64.
Progression-free survival, HR+ cohort (BICR) (months): Trastuzumab deruxtecan 10.1 (n=331) vs Chemotherapy (TPC) 5.4 (n=163) · HR 0.51 · source

The main trade-offs on record

Trastuzumab deruxtecan all recorded rates →

Side effect	Any grade	Grade 3+
Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	18%
Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	6%

Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision

Is Trastuzumab deruxtecan the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
Why: A single standard does not mean a single choice; timing and trials are decisions too.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in DESTINY-Breast04, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
For my situation (after one or two lines of chemotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).
Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of DESTINY-Breast04 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Triple-negative HER2-low disease

3 optionsCompare side by side →

TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.

The options, in plain words

Sacituzumab govitecanApprovedADC

The first TROP2-targeted ADC. It delivers a strong chemotherapy directly to breast and bladder cancer cells and is now a first-line option in triple-negative breast cancer.

Datopotamab deruxtecanApprovedADC

Datopotamab deruxtecan (Datroway) is the second TROP2 ADC and shares Enhertu's payload. In 2026 it became a first-line option for triple-negative breast cancer patients who cannot receive immunotherapy.

Trastuzumab deruxtecanApprovedADC

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

The evidence behind it

ASCENT Phase 3 NCT02574455 2020529 peopleevidence 88
Tests Sacituzumab govitecan
Pretreated metastatic TNBC: sacituzumab govitecan vs chemotherapy
OS 12.1 vs 6.7 months, HR 0.48.
Progression-free survival (patients without brain metastases) (months): Sacituzumab govitecan 5.6 (n=235) vs Chemotherapy (TPC) 1.7 (n=233) · HR 0.41 · source
TROPION-Breast02 Phase 3 NCT05374512 2025644 peopleevidence 88
Tests Datopotamab deruxtecan
First-line metastatic TNBC, not candidates for PD-1/PD-L1: Dato-DXd vs chemotherapy
OS 23.7 vs 18.7 months; PFS also improved.
Progression-free survival (BICR) (months): Datopotamab deruxtecan 10.8 (n=323) vs Chemotherapy (ICC) 5.6 (n=321) · HR 0.57 · source

The main trade-offs on record

Sacituzumab govitecan all recorded rates →

Side effect	Any grade	Grade 3+
Neutropenia · ASCENT, Trodelvy arm, n=258	78%	49%
Diarrhoea · ASCENT, Trodelvy arm, n=258	59%	11%
Anaemia · ASCENT, Trodelvy arm, n=258	94%	9%
Fatigue · ASCENT, Trodelvy arm, n=258	65%	6%

UGT1A1*28 homozygotes: higher neutropenia risk; G-CSF prophylaxis is often used.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Datopotamab deruxtecan all recorded rates →

Side effect	Any grade	Grade 3+
Stomatitis · TROPION-Breast01, n=360	59%	7%
Fatigue · TROPION-Breast01, n=360	44%	4.2%
Nausea · TROPION-Breast01, n=360	56%	1.4%
Keratitis · TROPION-Breast01, n=360	24%	1.1%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Trastuzumab deruxtecan all recorded rates →

Side effect	Any grade	Grade 3+
Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	18%
Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	7%
Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label	-	6%

Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision

Between Sacituzumab govitecan, Datopotamab deruxtecan and Trastuzumab deruxtecan, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in ASCENT and TROPION-Breast02, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Sacituzumab govitecan or Datopotamab deruxtecan are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
For my situation (triple-negative her2-low disease), which of the standard options do you recommend and why?
Why: Guideline options include: TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.
Am I a candidate for Sacituzumab govitecan, Datopotamab deruxtecan, Trastuzumab deruxtecan, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of ASCENT and TROPION-Breast02 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Lung toxicity

One path named

Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.

The path, in plain words

CT (computed tomography)Standard of care

A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread.

Fast, ubiquitous
Sub-millimetre resolution
Standard for RECIST response

Also referenced:Interstitial lung disease (ILD) / pneumonitis

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

CT (computed tomography)

Anatomic only; cannot distinguish scar from live tumour
Radiation dose
Poor for brain, marrow, and small peritoneal disease

Questions to ask about this decision

Is CT (computed tomography) the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
Why: A single standard does not mean a single choice; timing and trials are decisions too.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
For my situation (lung toxicity), which of the standard options do you recommend and why?
Why: Guideline options include: Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.